mouse cochlear nucleus: Topics by Science.gov

Sample records for mouse cochlear nucleus

Altered vesicular glutamate transporter distributions in the mouse cochlear nucleus following cochlear insult

PubMed Central

Heeringa, Amarins N.; Stefanescu, Roxana A.; Raphael, Yehoash; Shore, Susan E.

2015-01-01

Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to the sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e. in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration. PMID:26705736
Altered vesicular glutamate transporter distributions in the mouse cochlear nucleus following cochlear insult.

PubMed

Heeringa, A N; Stefanescu, R A; Raphael, Y; Shore, S E

2016-02-19

Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e., in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Olivocochlear neuron central anatomy is normal in alpha 9 knockout mice.

PubMed

Brown, M Christian; Vetter, Douglas E

2009-03-01

Olivocochlear (OC) neurons were studied in a transgenic mouse with deletion of the alpha 9 nicotinic acetylcholine receptor subunit. In this alpha 9 knockout mouse, the peripheral effects of OC stimulation are lacking and the peripheral terminals of OC neurons under outer hair cells have abnormal morphology. To account for this mouse's apparently normal hearing, it has been proposed to have central compensation via collateral branches to the cochlear nucleus. We tested this idea by staining OC neurons for acetylcholinesterase and examining their morphology in knockout mice, wild-type mice of the same background strain, and CBA/CaJ mice. Knockout mice had normal OC systems in terms of numbers of OC neurons, dendritic patterns, and numbers of branches to the cochlear nucleus. The branch terminations were mainly to edge regions and to a lesser extent the core of the cochlear nucleus, and were similar among the strains in terms of the distribution and staining density. These data demonstrate that there are no obvious changes in the central morphology of the OC neurons in alpha 9 knockout mice and make less attractive the idea that there is central compensation for deletion of the peripheral receptor in these mice.
Commissural axons of the mouse cochlear nucleus.

PubMed

Brown, M Christian; Drottar, Marie; Benson, Thane E; Darrow, Keith

2013-05-01

The axons of commissural neurons that project from one cochlear nucleus to the other were studied after labeling with anterograde tracer. Injections were made into the dorsal subdivision of the cochlear nucleus in order to restrict labeling only to the group of commissural neurons that gave off collaterals to, or were located in, this subdivision. The number of labeled commissural axons in each injection was correlated with the number of labeled radiate multipolar neurons, suggesting radiate neurons as the predominant origin of the axons. The radiate commissural axons are thick and myelinated, and they exit the dorsal acoustic stria of the injected cochlear nucleus to cross the brainstem in the dorsal half, near the crossing position of the olivocochlear bundle. They enter the opposite cochlear nucleus via the dorsal and ventral acoustic stria and at its medial border. Reconstructions of single axons demonstrate that terminations are mostly in the core and typically within a single subdivision of the cochlear nucleus. Extents of termination range from narrow to broad along both the dorsoventral (i.e., tonotopic) and the rostrocaudal dimensions. In the electron microscope, labeled swellings form synapses that are symmetric (in that there is little postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons do not appear to include excitatory commissural axons that end in edge regions of the nucleus. Radiate commissural axons could mediate the broadband inhibition observed in responses to contralateral sound, and they may balance input from the two ears with a quick time course. Copyright © 2012 Wiley Periodicals, Inc.
Commissural Axons of the Mouse Cochlear Nucleus

PubMed Central

Brown, M. Christian; Drottar, Marie; Benson, Thane E.; Darrow, Keith

2012-01-01

The axons of commissural neurons that project from one cochlear nucleus to the other were studied after labeling with anterograde tracer. Injections were made into the dorsal subdivision of the cochlear nucleus in order to restrict labeling only to the group of commissural neurons that gave off collaterals to, or were located in, this subdivision. The number of labeled commissural axons in each injection was correlated with the number of labeled radiate multipolar neurons, suggesting radiate neurons as the predominant origin of the axons. The radiate commissural axons are thick and myelinated, and they exit the dorsal acoustic stria of the injected cochlear nucleus to cross the brainstem in the dorsal half, near the crossing position of the olivocochlear bundle. They enter the opposite cochlear nucleus via the dorsal and ventral acoustic stria and at its medial border. Reconstructions of single axons demonstrate that terminations are mostly in the core and typically within a single subdivision of the cochlear nucleus. Extents of termination range from narrow to broad along both the dorso-ventral (i.e. tonotopic) and rostro-caudal dimensions. In the electron microscope, labeled swellings form synapses that are symmetric (in that there is little postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons do not appear to include excitatory commissural axons that end in edge regions of the nucleus. Radiate commissural axons could mediate the broad-band inhibition observed in responses to contralateral sound, and they may balance input from the two ears on a quick time course. PMID:23124982
IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1 and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.

PubMed

Fuentes-Santamaría, V; Alvarado, J C; Rodríguez-de la Rosa, L; Murillo-Cuesta, S; Contreras, J; Juiz, J M; Varela-Nieto, I

2016-03-01

Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a crucial role in modulating neuronal function and synaptic plasticity in the adult brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple anomalies in the inner ear and spiral ganglion. An issue that remains unknown is whether, in addition to these peripheral abnormalities, IGF-1 deficiency also results in structural changes along the central auditory pathway that may contribute to an imbalance between excitation and inhibition, which might be reflected in abnormal auditory brainstem responses (ABR). To assess such a possibility, we evaluated the morphological and physiological alterations in the cochlear nucleus complex of the adult mouse. The expression and distribution of the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory transporter (VGAT), which were used as specific markers for labeling excitatory and inhibitory terminals, and the involvement of the activity-dependent myocyte enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in the cochlear nucleus area and cell size along with cell loss in the cochlear nuclei of the deficient mouse. Additionally, our results demonstrate that there is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of MEF2 transcription factors together with increased wave II amplitude in the ABR recording. Our observations provide evidence of an abnormal neuronal cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that the increased efficacy of glutamatergic synapses might be mediated by MEF2 transcription factors.
Serotonin projection patterns to the cochlear nucleus.

PubMed

Thompson, A M; Thompson, G C

2001-07-13

The cochlear nucleus is well known as an obligatory relay center for primary auditory nerve fibers. Perhaps not so well known is the neural input to the cochlear nucleus from cells containing serotonin that reside near the midline in the midbrain raphe region. Although the specific locations of the main, if not sole, sources of serotonin within the dorsal cochlear nucleus subdivision are known to be the dorsal and median raphe nuclei, sources of serotonin located within other cochlear nucleus subdivisions are not currently known. Anterograde tract tracing was used to label fibers originating from the dorsal and median raphe nuclei while fluorescence immunohistochemistry was used to simultaneously label specific serotonin fibers in cat. Biotinylated dextran amine was injected into the dorsal and median raphe nuclei and was visualized with Texas Red, while serotonin was visualized with fluorescein. Thus, double-labeled fibers were unequivocally identified as serotoninergic and originating from one of the labeled neurons within the dorsal and median raphe nuclei. Double-labeled fiber segments, typically of fine caliber with oval varicosities, were observed in many areas of the cochlear nucleus. They were found in the molecular layer of the dorsal cochlear nucleus, in the small cell cap region, and in the granule cell and external regions of the cochlear nuclei, bilaterally, of all cats. However, the density of these double-labeled fiber segments varied considerably depending upon the exact region in which they were found. Fiber segments were most dense in the dorsal cochlear nucleus (especially in the molecular layer) and the large spherical cell area of the anteroventral cochlear nucleus; they were moderately dense in the small cell cap region; and fiber segments were least dense in the octopus and multipolar cell regions of the posteroventral cochlear nucleus. Because of the presence of labeled fiber segments in subdivisions of the cochlear nucleus other than the dorsal cochlear nucleus, we concluded that the serotoninergic projection pattern to the cochlear nucleus is divergent and non-specific. Double-labeled fiber segments were also present, but sparse, in the superior olive, localized mainly in periolivary regions; this indicated that the divergence of dorsal and median raphe neurons that extends throughout regions of the cochlear nucleus also extended well beyond the cochlear nucleus to include at least the superior olivary complex as well.
Developing a Mouse Model of Sensory and Cognitive Deficits for Multiple Sclerosis

DTIC Science & Technology

2013-07-01

the plot is essentially horizontal, indicating that these mutants cannot localize sounds in space. A well-known characteristic of signal flow ...the five characteristic peaks and troughs of the ABR arising from generators in the eighth cranial nerve, cochlear nucleus, SOC, lateral lemniscus and
Spiral Ganglion Neuron Projection Development to the Hindbrain in Mice Lacking Peripheral and/or Central Target Differentiation

PubMed Central

Elliott, Karen L.; Kersigo, Jennifer; Pan, Ning; Jahan, Israt; Fritzsch, Bernd

2017-01-01

We investigate the importance of the degree of peripheral or central target differentiation for mouse auditory afferent navigation to the organ of Corti and auditory nuclei in three different mouse models: first, a mouse in which the differentiation of hair cells, but not central auditory nuclei neurons is compromised (Atoh1-cre; Atoh1f/f); second, a mouse in which hair cell defects are combined with a delayed defect in central auditory nuclei neurons (Pax2-cre; Atoh1f/f), and third, a mouse in which both hair cells and central auditory nuclei are absent (Atoh1−/−). Our results show that neither differentiated peripheral nor the central target cells of inner ear afferents are needed (hair cells, cochlear nucleus neurons) for segregation of vestibular and cochlear afferents within the hindbrain and some degree of base to apex segregation of cochlear afferents. These data suggest that inner ear spiral ganglion neuron processes may predominantly rely on temporally and spatially distinct molecular cues in the region of the targets rather than interaction with differentiated target cells for a crude topological organization. These developmental data imply that auditory neuron navigation properties may have evolved before auditory nuclei. PMID:28450830
Effect of cochlear nerve electrocautery on the adult cochlear nucleus.

PubMed

Iseli, Claire E; Merwin, William H; Klatt-Cromwell, Cristine; Hutson, Kendall A; Ewend, Matthew G; Adunka, Oliver F; Fitzpatrick, Douglas C; Buchman, Craig A

2015-04-01

Electrocauterization and subsequent transection of the cochlear nerve induce greater injury to the cochlear nucleus than sharp transection alone. Some studies show that neurofibromatosis Type 2 (NF2) patients fit with auditory brainstem implants (ABIs) fail to achieve speech perception abilities similar to ABI recipients without NF2. Reasons for these differences remain speculative. One hypothesis posits poorer performance to surgically induced trauma to the cochlear nucleus from electrocautery. Sustained electrosurgical depolarization of the cochlear nerve may cause excitotoxic-induced postsynaptic nuclear injury. Equally plausible is that cautery in the vicinity of the cochlear nucleus induces necrosis. The cochlear nerve was transected in anesthetized adult gerbils sharply with or without bipolar electrocautery at varying intensities. Gerbils were perfused at 1, 3, 5, and 7 days postoperatively; their brainstem and cochleas were embedded in paraffin and sectioned at 10 μm. Alternate sections were stained with flourescent markers for neuronal injury or Nissl substance. In additional experiments, anterograde tracers were applied directly to a sectioned eighth nerve to verify that fluorescent-labeled profiles seen were terminating auditory nerve fibers. Cochlear nerve injury was observed from 72 hours postoperatively and was identical across cases regardless of surgical technique. Postsynaptic cochlear nucleus injury was not seen after distal transection of the nerve. By contrast, proximal transection was associated with trauma to the cochlear nucleus. Distal application of bipolar electrocautery seems safe for the cochlear nucleus. Application near the root entry zone must be used cautiously because this may compromise nuclear viability needed to support ABI stimulation.
Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons.

PubMed

Tong, Ling; Strong, Melissa K; Kaur, Tejbeer; Juiz, Jose M; Oesterle, Elizabeth C; Hume, Clifford; Warchol, Mark E; Palmiter, Richard D; Rubel, Edwin W

2015-05-20

During nervous system development, critical periods are usually defined as early periods during which manipulations dramatically change neuronal structure or function, whereas the same manipulations in mature animals have little or no effect on the same property. Neurons in the ventral cochlear nucleus (CN) are dependent on excitatory afferent input for survival during a critical period of development. Cochlear removal in young mammals and birds results in rapid death of target neurons in the CN. Cochlear removal in older animals results in little or no neuron death. However, the extent to which hair-cell-specific afferent activity prevents neuronal death in the neonatal brain is unknown. We further explore this phenomenon using a new mouse model that allows temporal control of cochlear hair cell deletion. Hair cells express the human diphtheria toxin (DT) receptor behind the Pou4f3 promoter. Injections of DT resulted in nearly complete loss of organ of Corti hair cells within 1 week of injection regardless of the age of injection. Injection of DT did not influence surrounding supporting cells directly in the sensory epithelium or spiral ganglion neurons (SGNs). Loss of hair cells in neonates resulted in rapid and profound neuronal loss in the ventral CN, but not when hair cells were eliminated at a more mature age. In addition, normal survival of SGNs was dependent on hair cell integrity early in development and less so in mature animals. This defines a previously undocumented critical period for SGN survival. Copyright © 2015 the authors 0270-6474/15/357878-14$15.00/0.
Response Properties of Cochlear Nucleus Neurons in Monkeys

PubMed Central

Roth, G. Linn; Recio, A.

2009-01-01

Much of what is known about how the cochlear nuclei participate in mammalian hearing comes from studies of non-primate mammalian species. To determine to what extent the cochlear nuclei of primates resemble those of other mammalian orders, we have recorded responses to sound in three primate species: marmosets, Cynomolgus macaques, and squirrel monkeys. These recordings show that the same types of temporal firing patterns are found in primates that have been described in other mammals. Responses to tones of neurons in the ventral cochlear nucleus have similar tuning, latencies, post-stimulus time and interspike interval histograms as those recorded in non-primate cochlear nucleus neurons. In the dorsal cochlear nucleus, too, responses were similar. From these results it is evident that insights gained from non-primate studies can be applied to the peripheral auditory system of primates. PMID:19531377
Changing patterns of peanut agglutinin labelling in the dorsal cochlear nucleus correspond to axonal ingrowth.

PubMed Central

Riggs, G H; Schweitzer, L

1994-01-01

Various studies have suggested that glycoconjugates may influence connectivity and lamination in the developing central nervous system and may function as barriers to neuritic extension. It has been proposed that the peanut agglutinin lectin labels a glycoconjugate subserving a barrier function. We chose to investigate the distribution of this peanut-agglutinin-labelled glycoconjugate in the dorsal cochlear nucleus of the developing hamster since the development of the dorsal cochlear nucleus is well characterised and its axons obey laminar boundaries. The distribution of peanut agglutinin label throughout the cochlear nucleus delineated zones that cochlear axons fail to invade. In the dorsal cochlear nucleus, laminar differences were reduced on postnatal d 13 and virtually disappearing by postnatal d 23. Label in the molecular layer dissipated as axons and dendrites grew into this layer. These patterns of peanut agglutinin binding correspond to axonal ingrowth and are consistent with a barrier function for glycoconjugates in the molecular layer. Images Fig. 1 Fig. 2 Fig. 4 PMID:7961144
Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem.

PubMed

Karmakar, Kajari; Narita, Yuichi; Fadok, Jonathan; Ducret, Sebastien; Loche, Alberto; Kitazawa, Taro; Genoud, Christel; Di Meglio, Thomas; Thierry, Raphael; Bacelo, Joao; Lüthi, Andreas; Rijli, Filippo M

2017-01-03

Tonotopy is a hallmark of auditory pathways and provides the basis for sound discrimination. Little is known about the involvement of transcription factors in brainstem cochlear neurons orchestrating the tonotopic precision of pre-synaptic input. We found that in the absence of Hoxa2 and Hoxb2 function in Atoh1-derived glutamatergic bushy cells of the anterior ventral cochlear nucleus, broad input topography and sound transmission were largely preserved. However, fine-scale synaptic refinement and sharpening of isofrequency bands of cochlear neuron activation upon pure tone stimulation were impaired in Hox2 mutants, resulting in defective sound-frequency discrimination in behavioral tests. These results establish a role for Hox factors in tonotopic refinement of connectivity and in ensuring the precision of sound transmission in the mammalian auditory circuit. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Auditory Spatial Perception: Auditory Localization

DTIC Science & Technology

2012-05-01

cochlear nucleus, TB – trapezoid body, SOC – superior olivary complex, LL – lateral lemniscus, IC – inferior colliculus. Adapted from Aharonson and...Figure 5. Auditory pathways in the central nervous system. LE – left ear, RE – right ear, AN – auditory nerve, CN – cochlear nucleus, TB...fibers leaving the left and right inner ear connect directly to the synaptic inputs of the cochlear nucleus (CN) on the same (ipsilateral) side of
Survival, migration, and differentiation of Sox1-GFP embryonic stem cells in coculture with an auditory brainstem slice preparation.

PubMed

Glavaski-Joksimovic, Aleksandra; Thonabulsombat, Charoensri; Wendt, Malin; Eriksson, Mikael; Palmgren, Björn; Jonsson, Anna; Olivius, Petri

2008-03-01

The poor regeneration capability of the mammalian hearing organ has initiated different approaches to enhance its functionality after injury. To evaluate a potential neuronal repair paradigm in the inner ear and cochlear nerve we have previously used embryonic neuronal tissue and stem cells for implantation in vivo and in vitro. At present, we have used in vitro techniques to study the survival and differentiation of Sox1-green fluorescent protein (GFP) mouse embryonic stem (ES) cells as a monoculture or as a coculture with rat auditory brainstem slices. For the coculture, 300 microm-thick brainstem slices encompassing the cochlear nucleus and cochlear nerve were prepared from postnatal SD rats. The slices were propagated using the membrane interface method and the cochlear nuclei were prelabeled with DiI. After some days in culture a suspension of Sox1 cells was deposited next to the brainstem slice. Following deposition Sox1 cells migrated toward the brainstem and onto the cochlear nucleus. GFP was not detectable in undifferentiated ES cells but became evident during neural differentiation. Up to 2 weeks after transplantation the cocultures were fixed. The undifferentiated cells were evaluated with antibodies against progenitor cells whereas the differentiated cells were determined with neuronal and glial markers. The morphological and immunohistochemical data indicated that Sox1 cells in monoculture differentiated into a higher percentage of glial cells than neurons. However, when a coculture was used a significantly lower percentage of Sox1 cells differentiated into glial cells. The results demonstrate that a coculture of Sox1 cells and auditory brainstem present a useful model to study stem cell differentiation.
Effects of Nicotine and Nicotinic Antagonists on the Acoustic Startle Response and on Pre-Pulse Inhibition in Rats

DTIC Science & Technology

1996-06-07

the auditory nerve, the ventral cochlear nucleus , nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, spinal neuron, and lower... nucleus , nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, hippocampus, and striatum (Davis, et al., 1982; Swerdlow, et aI, 1992...Davis, M. (1985) Cocaine effects on acoustic startle and startle elicited electrically from cochlear nucleus . P§ychQpharmacology, 87, 396-399 James
Effects of cochlear ablation on choline acetyltransferase activity in the rat cochlear nucleus and superior olive.

PubMed

Jin, Yong-Ming; Godfrey, Donald A; Sun, Yizhe

2005-07-01

Using microdissection and quantitative microassay, choline acetyltransferase (ChAT) activity was mapped in the cochlear nucleus (CN) and in the source nuclei of the olivocochlear bundle, the lateral superior olive and ventral nucleus of the trapezoid body. In control rats, gradients of ChAT activity were found within the major subdivisions of the CN and in the lateral superior olive. These gradients correlated with the known tonotopic organizations, with higher activities corresponding to locations representing higher sound frequencies. No gradient was found in the ventral nucleus of the trapezoid body. In rats surviving 7 days or 1 or 2 months after cochlear ablation, ChAT activity was increased 1 month after ablation in the anteroventral CN by 30-50% in most parts of the lesion-side and by 40% in the contralateral ventromedial part. ChAT activity in the lesion-side posteroventral CN was increased by approximately 40-50% at all survival times. Little change was found in the dorsal CN. Decreases of ChAT activity were also found ipsilaterally in the lateral superior olive and bilaterally in the ventral nucleus of the trapezoid body. Our results suggest that cholinergic neurons are involved in plasticity within the CN and superior olive following cochlear lesions. Copyright 2005 Wiley-Liss, Inc.
Low Level Chemical Toxicity: Relevance to Chemical Agent Defense

DTIC Science & Technology

2005-07-01

elevation in stress hormones in the blood serum. Electron microscropy indicated no damage to cochlear tissues of the ear (not shown). At the...neural activity occurring primarily in the cochlear nucleus of the brainstem auditory pathway. Peak II is usually the last major peak to disappear...IV). Peak II is generally the strongest peak and is regarded as a putative indicator of neural activity occurring primarily in the cochlear nucleus
The development of the Nucleus Freedom Cochlear implant system.

PubMed

Patrick, James F; Busby, Peter A; Gibson, Peter J

2006-12-01

Cochlear Limited (Cochlear) released the fourth-generation cochlear implant system, Nucleus Freedom, in 2005. Freedom is based on 25 years of experience in cochlear implant research and development and incorporates advances in medicine, implantable materials, electronic technology, and sound coding. This article presents the development of Cochlear's implant systems, with an overview of the first 3 generations, and details of the Freedom system: the CI24RE receiver-stimulator, the Contour Advance electrode, the modular Freedom processor, the available speech coding strategies, the input processing options of Smart Sound to improve the signal before coding as electrical signals, and the programming software. Preliminary results from multicenter studies with the Freedom system are reported, demonstrating better levels of performance compared with the previous systems. The final section presents the most recent implant reliability data, with the early findings at 18 months showing improved reliability of the Freedom implant compared with the earlier Nucleus 3 System. Also reported are some of the findings of Cochlear's collaborative research programs to improve recipient outcomes. Included are studies showing the benefits from bilateral implants, electroacoustic stimulation using an ipsilateral and/or contralateral hearing aid, advanced speech coding, and streamlined speech processor programming.

Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus.

PubMed

Verma, Rohit U; Guex, Amélie A; Hancock, Kenneth E; Durakovic, Nedim; McKay, Colette M; Slama, Michaël C C; Brown, M Christian; Lee, Daniel J

2014-04-01

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. Copyright © 2014 Elsevier B.V. All rights reserved.
Auditory Responses to Electric and Infrared Neural Stimulation of the Rat Cochlear Nucleus

PubMed Central

Verma, Rohit; Guex, Amelie A.; Hancock, Kenneth E.; Durakovic, Nedim; McKay, Colette M.; Slama, Michaël C. C.; Brown, M. Christian; Lee, Daniel J.

2014-01-01

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported “optophonic” effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. PMID:24508368
Effects of input processing and type of personal frequency modulation system on speech-recognition performance of adults with cochlear implants.

PubMed

Wolfe, Jace; Schafer, Erin; Parkinson, Aaron; John, Andrew; Hudson, Mary; Wheeler, Julie; Mucci, Angie

2013-01-01

The objective of this study was to compare speech recognition in quiet and in noise for cochlear implant recipients using two different types of personal frequency modulation (FM) systems (directly coupled [direct auditory input] versus induction neckloop) with each of two sound processors (Cochlear Nucleus Freedom versus Cochlear Nucleus 5). Two different experiments were conducted within this study. In both these experiments, mixing of the FM signal within the Freedom processor was implemented via the same scheme used clinically for the Freedom sound processor. In Experiment 1, the aforementioned comparisons were conducted with the Nucleus 5 programmed so that the microphone and FM signals were mixed and then the mixed signals were subjected to autosensitivity control (ASC). In Experiment 2, comparisons between the two FM systems and processors were conducted again with the Nucleus 5 programmed to provide a more complex multistage implementation of ASC during the preprocessing stage. This study was a within-subject, repeated-measures design. Subjects were recruited from the patient population at the Hearts for Hearing Foundation in Oklahoma City, OK. Fifteen subjects participated in Experiment 1, and 16 subjects participated in Experiment 2. Subjects were adults who had used either unilateral or bilateral cochlear implants for at least 1 year. In this experiment, no differences were found in speech recognition in quiet obtained with the two different FM systems or the various sound-processor conditions. With each sound processor, speech recognition in noise was better with the directly coupled direct auditory input system relative to the neckloop system. The multistage ASC processing of the Nucleus 5 sound processor provided better performance than the single-stage approach for the Nucleus 5 and the Nucleus Freedom sound processor. Speech recognition in noise is substantially affected by the type of sound processor, FM system, and implementation of ASC used by a Cochlear implant recipient.
Intrinsic and synaptic properties of vertical cells of the mouse dorsal cochlear nucleus

PubMed Central

Kuo, Sidney P.; Lu, Hsin-Wei

2012-01-01

Multiple classes of inhibitory interneurons shape the activity of principal neurons of the dorsal cochlear nucleus (DCN), a primary target of auditory nerve fibers in the mammalian brain stem. Feedforward inhibition mediated by glycinergic vertical cells (also termed tuberculoventral or corn cells) is thought to contribute importantly to the sound-evoked response properties of principal neurons, but the cellular and synaptic properties that determine how vertical cells function are unclear. We used transgenic mice in which glycinergic neurons express green fluorescent protein (GFP) to target vertical cells for whole cell patch-clamp recordings in acute slices of DCN. We found that vertical cells express diverse intrinsic spiking properties and could fire action potentials at high, sustained spiking rates. Using paired recordings, we directly examined synapses made by vertical cells onto fusiform cells, a primary DCN principal cell type. Vertical cell synapses produced unexpectedly small-amplitude unitary currents in fusiform cells, and additional experiments indicated that multiple vertical cells must be simultaneously active to inhibit fusiform cell spike output. Paired recordings also revealed that a major source of inhibition to vertical cells comes from other vertical cells. PMID:22572947
Medial Auditory Thalamus Is Necessary for Acquisition and Retention of Eyeblink Conditioning to Cochlear Nucleus Stimulation

ERIC Educational Resources Information Center

Halverson, Hunter E.; Poremba, Amy; Freeman, John H.

2015-01-01

Associative learning tasks commonly involve an auditory stimulus, which must be projected through the auditory system to the sites of memory induction for learning to occur. The cochlear nucleus (CN) projection to the pontine nuclei has been posited as the necessary auditory pathway for cerebellar learning, including eyeblink conditioning.…
Pyridostigmine-Induced Neurodegeneration: Role of Neuronal Apoptosis.

DTIC Science & Technology

1999-10-01

carbachol releases glutamate and glycine from dorsal cochlear nucleus brain slices (Chen et al, 1999). No other amino acids were released from brain...Sivasamy (1997) reported that the anticholinesterase, phosphamidon, caused apoptosis in spermatogenic line cells. Also, muscarinic agonists, carbachol and...1999) Glutamergic transmission of neuronal responses to carbachol in rat cochlear nucleus slices. Neurosci. 90: 2043-2049. Crews, F.T., Steck, J.C
Cerebellar interaction with the acoustic reflex.

PubMed

Jastreboff, P J

1981-01-01

The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc.
Gain and frequency tuning within the mouse cochlear apex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oghalai, John S.; Raphael, Patrick D.; Gao, Simon

Normal mammalian hearing requires cochlear outer hair cell active processes that amplify the traveling wave with high gain and sharp tuning, termed cochlear amplification. We have used optical coherence tomography to study cochlear amplification within the apical turn of the mouse cochlea. We measured not only classical basilar membrane vibratory tuning curves but also vibratory responses from the rest of the tissues that compose the organ of Corti. Basilar membrane tuning was sharp in live mice and broad in dead mice, whereas other regions of the organ of Corti demonstrated phase shifts consistent with additional filtering beyond that provided bymore » basilar membrane mechanics. We use these experimental data to support a conceptual framework of how cochlear amplification is tuned within the mouse cochlear apex. We will also study transgenic mice with targeted mutations that affect different biomechanical aspects of the organ of Corti in an effort to localize the underlying processes that produce this additional filtering.« less
Signal Processing, Pattern Formation and Adaptation in Neural Oscillators

DTIC Science & Technology

2016-11-29

nonlinear oscillations of outer hair cells. We obtained analytical forms for auditory tuning curves of both unidirectionally and bidirectionally coupled...oscillations of outer hair cells in the cochlea, mode-locking of chopper cells to sound in the cochlear nucleus, and entrainment of cortical...oscillations of outer hair cells (e.g., Fredrickson-Hemsing, Ji, Bruinsma, & Bozovic, 2012), mode-locking of choppers in the cochlear nucleus (e.g., Laudanski
Glutamate co-transmission from developing medial nucleus of the trapezoid body - Lateral superior olive synapses is cochlear dependent in kanamycin-treated rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jae Ho; Pradhan, Jonu; Maskey, Dhiraj

Research highlights: {yields} Glutamate co-transmission is enhanced in kanamycin-treated rats. {yields} VGLUT3 expression is increased in kanamycin-treated rats. {yields} GlyR expression is decreased in kanamycin-treated rats. {yields} GlyR, VGLUT3 expression patterns are asymmetric in unilaterally cochlear ablated rat. -- Abstract: Cochlear dependency of glutamate co-transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses was investigated using developing rats treated with high dose kanamycin. Rats were treated with kanamycin from postnatal day (P) 3 to P8. A scanning electron microscopic study on P9 demonstrated partial cochlear hair cell damage. A whole cell voltagemore » clamp experiment demonstrated the increased glutamatergic portion of postsynaptic currents (PSCs) elicited by MNTB stimulation in P9-P11 kanamycin-treated rats. The enhanced VGLUT3 immunoreactivities (IRs) in kanamycin-treated rats and asymmetric VGLUT3 IRs in the LSO of unilaterally cochlear ablated rats supported the electrophysiologic data. Taken together, it is concluded that glutamate co-transmission is cochlear-dependent and enhanced glutamate co-transmission in kanamycin-treated rats is induced by partial cochlear damage.« less
Remote programming of cochlear implants: a telecommunications model.

PubMed

McElveen, John T; Blackburn, Erin L; Green, J Douglas; McLear, Patrick W; Thimsen, Donald J; Wilson, Blake S

2010-09-01

Evaluate the effectiveness of remote programming for cochlear implants. Retrospective review of the cochlear implant performance for patients who had undergone mapping and programming of their cochlear implant via remote connection through the Internet. Postoperative Hearing in Noise Test and Consonant/Nucleus/Consonant word scores for 7 patients who had undergone remote mapping and programming of their cochlear implant were compared with the mean scores of 7 patients who had been programmed by the same audiologist over a 12-month period. Times required for remote and direct programming were also compared. The quality of the Internet connection was assessed using standardized measures. Remote programming was performed via a virtual private network with a separate software program used for video and audio linkage. All 7 patients were programmed successfully via remote connectivity. No untoward patient experiences were encountered. No statistically significant differences could be found in comparing postoperative Hearing in Noise Test and Consonant/Nucleus/Consonant word scores for patients who had undergone remote programming versus a similar group of patients who had their cochlear implant programmed directly. Remote programming did not require a significantly longer programming time for the audiologist with these 7 patients. Remote programming of a cochlear implant can be performed safely without any deterioration in the quality of the programming. This ability to remotely program cochlear implant patients gives the potential to extend cochlear implantation to underserved areas in the United States and elsewhere.
A surgical approach appropriate for targeted cochlear gene therapy in the mouse.

PubMed

Jero, J; Tseng, C J; Mhatre, A N; Lalwani, A K

2001-01-01

Therapeutic manipulations of the mammalian cochlea, including cochlear gene transfer, have been predominantly studied using the guinea pig as the experimental model. With the significant developments in mouse genomics and the availability of mutant strains of mice with well-characterized hearing loss, the mouse justifiably will be the preferred animal model for therapeutic manipulations. However, the potential advantages of the mouse model have not been fully realized due to the surgical difficulty of accessing its small cochlea. This study describes a ventral approach, instead of the routinely used postauricular approach in other rodents, for accessing the mouse middle and inner ear, and its application in cochlear gene transfer. This ventral approach enabled rapid and direct delivery of liposome-transgene complex to the mouse inner ear while avoiding blood loss, facial nerve morbidity, and mortality. Transgene expression at 3 days was detected in Reissner's membrane, spiral limbus, spiral ligament, and spiral ganglion cells, in a pattern similar to that previously described in the guinea pig. The successful access and delivery of material to the mouse cochlea and the replication of gene expression seen in the guinea pig demonstrated in this study should promote the use of the mouse in future studies investigating targeted cochlear therapy.
Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates.

PubMed

Kandathil, Cherian K; Stakhovskaya, Olga; Leake, Patricia A

2016-12-01

Many previous studies have shown significant neurotrophic effects of intracochlear delivery of BDNF in preventing degeneration of cochlear spiral ganglion (SG) neurons after deafness in rodents and our laboratory has shown similar results in developing cats deafened prior to hearing onset. This study examined the morphology of the cochlear nucleus (CN) in a group of neonatally deafened cats from a previous study in which infusion of BDNF elicited a significant improvement in survival of the SG neurons. Five cats were deafened by systemic injections of neomycin sulfate (60 mg/kg, SQ, SID) starting one day after birth, and continuing for 16-18 days until auditory brainstem response (ABR) testing demonstrated profound bilateral hearing loss. The animals were implanted unilaterally at about 1 month of age using custom-designed electrodes with a drug-delivery cannula connected to an osmotic pump. BDNF (94 μg/ml; 0.25 μl/hr) was delivered for 10 weeks. The animals were euthanized and studied at 14-23 weeks of age. Consistent with the neurotrophic effects of BDNF on SG survival, the total CN volume in these animals was significantly larger on the BDNF-treated side than on the contralateral side. However, total CN volume, both ipsi- and contralateral to the implants in these deafened juvenile animals, was markedly smaller than the CN in normal adult animals, reflecting the severe effects of deafness on the central auditory system during development. Data from the individual major CN subdivisions (DCN, Dorsal Cochlear Nucleus; PVCN, Posteroventral Cochlear Nucleus; AVCN, Anteroventral Cochlear Nucleus) also were analyzed. A significant difference was observed between the BDNF-treated and control sides only in the AVCN. Measurements of the cross-sectional areas of spherical cells showed that cells were significantly larger in the AVCN ipsilateral to the implant than on the contralateral side. Further, the numerical density of spherical cells was significantly lower in the AVCN ipsilateral to the implant than on the contralateral side, consistent with the larger AVCN volume observed with BDNF treatment. Together, findings indicate significant neurotrophic effects of intracochlear BDNF infusion on the developing CN. Copyright © 2016 Elsevier B.V. All rights reserved.
Choline acetyltransferase, glutamate decarboxylase and tyrosine hydroxylase in the cochlea and cochlear nucleus of the guinea pig.

PubMed

Fex, J; Wenthold, R J

1976-06-18

Activities of choline acetyltransferase (ChAC), glutamate decarboxylase (GAD) and tyrosine hydroxylase (TH), enzymes catalyzing the synthesis of acetylcholine (ACh), gamma-aminobutyric acid (GABA) and catecholamines, respectively, were measured in the cochlea and cochlear nucleus of the guinea pig. ChAc activity in the organ of Corti, third turn, was 1270 pmole ACh formed/min/mg protein (ChAc, 1270) and was higher than in turn 4 (ChAc, 543). ChAc activity was higher when the preparation included the inner hair cell region than when not. GAD activity in samples of turn 3 and 4 combined was low, 0.17 nmole GABA formed/min/mg protein (GAD, 0.17). All 3 enzymes were low in auditory nerve: ChAc, 1.7, GAD, 0.10 and TH, 1.0 pmole DOPA formed/min/mg protein. In the cochlear nucleus, the values were: ChAc, 129, GAD, 1.70 and TH, 2.7. The findings on the distribution of ChAc activity in the organ of Corti fit the hypothesis that the olivocochlear nerve fibers are cholinergic. Because of low GAD in the cochlea, GABA is unlikely to be transmitter in the organ of Corti. Similarly, it is unlikely that ACh, GABA or a catecholamine is a transmitter between the auditory nerve and the cochlear nucleus.
Auditory Environment across the Life Span of Cochlear Implant Users: Insights from Data Logging

ERIC Educational Resources Information Center

Busch, Tobias; Vanpoucke, Filiep; van Wieringen, Astrid

2017-01-01

Purpose: We describe the natural auditory environment of people with cochlear implants (CIs), how it changes across the life span, and how it varies between individuals. Method: We performed a retrospective cross-sectional analysis of Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from 1,501 people with CIs (ages 0-96…
Experiences from Auditory Brainstem Implantation (ABIs) in four paediatric patients.

PubMed

Lundin, Karin; Stillesjö, Fredrik; Nyberg, Gunnar; Rask-Andersen, Helge

2016-01-01

Indications for auditory brainstem implants (ABIs) have been widened from patients with neurofibromatosis type 2 (NF2) to paediatric patients with congenital cochlear malformations, cochlear nerve hypoplasia/aplasia, or cochlear ossification after meningitis. We present four ABI surgeries performed in children at Uppsala University Hospital in Sweden since 2009. Three children were implanted with implants from Cochlear Ltd. (Lane Cove, Australia) and one child with an implant from MedEl GMBH (Innsbruck, Austria). A boy with Goldenhar syndrome was implanted with a Cochlear Nucleus ABI24M at age 2 years (patient 1). Another boy with CHARGE syndrome was implanted with a Cochlear Nucleus ABI541 at age 2.5 years (patient 2). Another boy with post-ossification meningitis was implanted with a Cochlear Nucleus ABI24M at age 4 years (patient 3). A girl with cochlear aplasia was implanted with a MedEl Synchrony ABI at age 3 years (patient 4). In patients 1, 2, and 3, the trans-labyrinthine approach was used, and in patient 4 the retro-sigmoid approach was used. Three of the four children benefited from their ABIs and use it full time. Two of the full time users had categories of auditory performance (CAP) score of 4 at their last follow up visit (6 and 2.5 years postoperative) which means they can discriminate consistently any combination of two of Ling's sounds. One child has not been fully evaluated yet, but is a full time user and had CAP 2 (responds to speech sounds) after 3 months of ABI use. No severe side or unpleasant stimulation effects have been observed so far. There was one case of immediate electrode migration and one case of implant device failure after 6.5 years. ABI should be considered as an option in the rehabilitation of children with similar diagnoses.
Development of a phase-sensitive Fourier domain optical coherence tomography system to measure mouse organ of Corti vibrations in two cochlear turns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramamoorthy, Sripriya; Zhang, Yuan; Jacques, Steven

In this study, we have developed a phase-sensitive Fourier-domain optical coherence tomography system to simultaneously measure the in vivo inner ear vibrations in the hook area and second turn of the mouse cochlea. This technical development will enable measurement of intra-cochlear distortion products at ideal locations such as the distortion product generation site and reflection site. This information is necessary to un-mix the complex mixture of intra-cochlear waves comprising the DPOAE and thus leads to the non-invasive identification of the local region of cochlear damage.
A Psychophysics experimental software to evaluate electrical pitch discrimination in Nucleus cochlear implanted patients

NASA Astrophysics Data System (ADS)

Pérez Zaballos, M. T.; Ramos de Miguel, A.; Killian, M.; Ramos Macías, A.

2016-02-01

Multichannel electrode array design in cochlear implants has evolved into two major categories: straight and perimodiolar electrodes. When implanted, the former lies along the outer wall of the scala tympani, while the later are located closer to the modiolus, where the neural ends are. Therefore, a perimodiolar position of the electrode array could be expected to result in reduced stimulus thresholds and stimulating currents, increased dynamic range, and more localized stimulation of the neural elements. However, their advantage for pitch discrimination has not been conclusively stated. Therefore, in order to study electrode independence, a psychophysical software has been developed, making use of Nucleus Implant Communicator tools provided by Cochlear company under a research agreement. The application comprises a graphical interface to facilitate its use, since previous software has always required some type of computer language skills. It allows for customization of electrical pulse parameters, measurement of threshold and comfort levels, loudness balancing and alternative forced choice experiments to determine electrode discrimination in Nucleus© users.
Cannabinoids, cannabinoid receptors and tinnitus.

PubMed

Smith, Paul F; Zheng, Yiwen

2016-02-01

One hypothesis suggests that tinnitus is a form of sensory epilepsy, arising partly from neuronal hyperactivity in auditory regions of the brain such as the cochlear nucleus and inferior colliculus. Although there is currently no effective drug treatment for tinnitus, anti-epileptic drugs are used in some cases as a potential treatment option. There is increasing evidence to suggest that cannabinoid drugs, i.e. cannabinoid receptor agonists, can also have anti-epileptic effects, at least in some cases and in some parts of the brain. It has been reported that cannabinoid CB1 receptors and the endogenous cannabinoid, 2-arachidonylglycerol (2-AG), are expressed in the cochlear nucleus and that they are involved in the regulation of plasticity. This review explores the question of whether cannabinoid receptor agonists are likely to be pro- or anti-epileptic in the cochlear nucleus and therefore whether cannabinoids and Cannabis itself are likely to make tinnitus better or worse. Copyright © 2015 Elsevier B.V. All rights reserved.
The effect of progressive hearing loss on the morphology of endbulbs of Held and bushy cells.

PubMed

Connelly, Catherine J; Ryugo, David K; Muniak, Michael A

2017-01-01

Studies of congenital and early-onset deafness have demonstrated that an absence of peripheral sound-evoked activity in the auditory nerve causes pathological changes in central auditory structures. The aim of this study was to establish whether progressive acquired hearing loss could lead to similar brain changes that would degrade the precision of signal transmission. We used complementary physiologic hearing tests and microscopic techniques to study the combined effect of both magnitude and duration of hearing loss on one of the first auditory synapses in the brain, the endbulb of Held (EB), along with its bushy cell (BC) target in the anteroventral cochlear nucleus. We compared two hearing mouse strains (CBA/Ca and heterozygous shaker-2 +/- ) against a model of early-onset progressive hearing loss (DBA/2) and a model of congenital deafness (homozygous shaker-2 -/- ), examining each strain at 1, 3, and 6 months of age. Furthermore, we employed a frequency model of the mouse cochlear nucleus to constrain our analyses to regions most likely to exhibit graded changes in hearing function with time. No significant differences in the gross morphology of EB or BC structure were observed in 1-month-old animals, indicating uninterrupted development. However, in animals with hearing loss, both EBs and BCs exhibited a graded reduction in size that paralleled the hearing loss, with the most severe pathology seen in deaf 6-month-old shaker-2 -/- mice. Ultrastructural pathologies associated with hearing loss were less dramatic: minor changes were observed in terminal size but mitochondrial fraction and postsynaptic densities remained relatively stable. These results indicate that acquired progressive hearing loss can have consequences on auditory brain structure, with prolonged loss leading to greater pathologies. Our findings suggest a role for early intervention with assistive devices in order to mitigate long-term pathology and loss of function. Copyright © 2016 Elsevier B.V. All rights reserved.

Bilateral cochlear implants in infants: a new approach--Nucleus Hybrid S12 project.

PubMed

Gantz, Bruce J; Dunn, Camille C; Walker, Elizabeth A; Kenworthy, Maura; Van Voorst, Tanya; Tomblin, Bruce; Turner, Chris

2010-10-01

The purpose of this feasibility study was to evaluate whether the use of a shorter-length cochlear implant (10 mm) on one ear and a standard electrode (24 mm) on the contralateral ear is a viable bilateral option for children with profound bilateral sensorineural hearing loss. A secondary purpose of this study was to determine whether the ear with the shorter-length electrode performs similarly to the standard-length electrode. Our goal was to provide an option of electrical stimulation that theoretically might preserve the structures of the scala media and organ of Corti. The study is being conducted as a repeated-measure, single-subject experiment. University of Iowa-Department of Otolaryngology. Eight pediatric patients with profound bilateral sensorineural hearing loss between the ages of 12 and 24 months. Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant in the contralateral ear. The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) parent questionnaire, Early Speech Perception, Glendonald Auditory Screening Procedure word test, and Children's Vowel tests will be used to evaluate speech perception and the Minnesota Child Development Inventory and Preschool Language Scales 3 test will be used to evaluate language growth. Preliminary results for 8 children have been collected before and after the operation using the IT-MAIS. All 3 children showed incremental improvements in their IT-MAIS scores overtime. Early Speech Perception, Glendonald Auditory Screening Procedure word test, and Children's Vowel word perception results indicated no difference between the individual ears for the 2 children tested. Performance compared with age-matched children implanted with standard bilateral cochlear implants showed similar results to the children implanted with Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant in contralateral ears. The use of a shorter-length cochlear implant on one ear and a standard-length electrode on the contralateral ear might provide a viable option for bilateral cochlear implantation in children with bilateral profound sensorineural hearing loss. Further study of this patient population will be continued.
Bilateral Cochlear Implants in Infants: A New Approach—Nucleus Hybrid S12 Project

PubMed Central

Gantz, Bruce J.; Dunn, Camille C.; Walker, Elizabeth A.; Kenworthy, Maura; Van Voorst, Tanya; Tomblin, Bruce; Turner, Chris

2010-01-01

Objective The purpose of this feasibility study was to evaluate whether the use of a shorter-length cochlear implant (10 mm) on one ear and a standard electrode (24 mm) on the contralateral ear is a viable bilateral option for children with profound bilateral sensorineural hearing loss. A secondary purpose of this study was to determine whether the ear with the shorter-length electrode performs similarly to the standard-length electrode. Our goal was to provide an option of electrical stimulation that theoretically might preserve the structures of the scala media and organ of Corti. Study Design The study is being conducted as a repeated-measure, single-subject experiment. Setting University of Iowa—Department of Otolaryngology. Patients Eight pediatric patients with profound bilateral sensorineural hearing loss between the ages of 12 and 24 months. Interventions Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant in the contralateral ear. Main Outcome Measures The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) parent questionnaire, Early Speech Perception, Glendonald Auditory Screening Procedure word test, and Children’s Vowel tests will be used to evaluate speech perception and the Minnesota Child Development Inventory and Preschool Language Scales 3 test will be used to evaluate language growth. Results Preliminary results for 8 children have been collected before and after the operation using the IT-MAIS. All 3 children showed incremental improvements in their IT-MAIS scores overtime. Early Speech Perception, Glendonald Auditory Screening Procedure word test, and Children’s Vowel word perception results indicated no difference between the individual ears for the 2 children tested. Performance compared with age-matched children implanted with standard bilateral cochlear implants showed similar results to the children implanted with Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant in contralateral ears. Conclusion The use of a shorter-length cochlear implant on one ear and a standard-length electrode on the contralateral ear might provide a viable option for bilateral cochlear implantation in children with bilateral profound sensorineural hearing loss. Further study of this patient population will be continued. PMID:20802369
Alteration of glycine receptor immunoreactivity in the auditory brainstem of mice following three months of exposure to radiofrequency radiation at SAR 4.0 W/kg.

PubMed

Maskey, Dhiraj; Kim, Hyung Gun; Suh, Myung-Whan; Roh, Gu Seob; Kim, Myeung Ju

2014-08-01

The increasing use of mobile communication has triggered an interest in its possible effects on the regulation of neurotransmitter signals. Due to the close proximity of mobile phones to hearing-related brain regions during usage, its use may lead to a decrease in the ability to segregate sounds, leading to serious auditory dysfunction caused by the prolonged exposure to radiofrequency (RF) radiation. The interplay among auditory processing, excitation and inhibitory molecule interactions plays a major role in auditory function. In particular, inhibitory molecules, such a glycine, are predominantly localized in the auditory brainstem. However, the effects of exposure to RF radiation on auditory function have not been reported to date. Thus, the aim of the present study was to investigate the effects of exposure to RF radiation on glycine receptor (GlyR) immunoreactivity (IR) in the auditory brainstem region at 835 MHz with a specific absorption rate of 4.0 W/kg for three months using free-floating immunohistochemistry. Compared with the sham control (SC) group, a significant loss of staining intensity of neuropils and cells in the different subdivisions of the auditory brainstem regions was observed in the mice exposed to RF radiation (E4 group). A decrease in the number of GlyR immunoreactive cells was also noted in the cochlear nuclear complex [anteroventral cochlear nucleus (AVCN), 31.09%; dorsal cochlear nucleus (DCN), 14.08%; posteroventral cochlear nucleus (PVCN), 32.79%] and the superior olivary complex (SOC) [lateral superior olivary nucleus (LSO), 36.85%; superior paraolivary nucleus (SPN), 24.33%, medial superior olivary nucleus (MSO), 23.23%; medial nucleus of the trapezoid body (MNTB), 10.15%] of the mice in the E4 group. Auditory brainstem response (ABR) analysis also revealed a significant threshold elevation of in the exposed (E4) group, which may be associated with auditory dysfunction. The present study suggests that the auditory brainstem region is susceptible to chronic exposure to RF radiation, which may affect the function of the central auditory system.
Postnatal development of microcyst in the anteroventral cochlear nucleus of the Mongolian gerbil: a light- and electron microscopic study.

PubMed

Yu, Shang-Ming; Ko, Tsui-Ling; Lin, Kwan-Hwa

2011-09-01

We investigated the postnatal formation and origin of the microcyst, which are not fully elucidated at present, in the cochlear nucleus of gerbils. Sixty-six Mongolian gerbils were investigated at the light microscope level, and 35 of them were observed at the electron microscopic level. Foamy structures were evidently found at 2 days of age and remained unchanged through 4-8 days. The first small vacuole, presumably the former microcyst, appeared at 8 days. Myelin sheath bundles first appeared at 13 days. Electron-dense bodies were frequently found in the junction of the superficial layer and the deep layer at 2 days. The medium-sized vacuole was found in close association with the spherical bushy cells in the anteroventral cochlear nucleus (AVCN) as early as 5 weeks. Various large and small vacuoles were presumably coalesced to form a large vacuole at 3 and 6 months. Membranous structures and red blood cells were in the budding-like vacuoles at 6 months. In addition to membranous structures, the microcyst contained distorted mitochondria and parts of myelin sheaths. The vacuole was interposed between spherical bushy cells at age of 10 months. Small vacuoles were mainly located in the flame-shaped neurons at 14 months. An internal detachment and an external protrusion of the myelin sheath into the adjacent microcyst were found. Thus, this study suggests the first appearance of microcysts at 8 days. Also, the microcyst and the blood vessel may exchange their contents through a leakage in the anteroventral cochlear nucleus.
Speech perception of young children using nucleus 22-channel or CLARION cochlear implants.

PubMed

Young, N M; Grohne, K M; Carrasco, V N; Brown, C

1999-04-01

This study compares the auditory perceptual skill development of 23 congenitally deaf children who received the Nucleus 22-channel cochlear implant with the SPEAK speech coding strategy, and 20 children who received the CLARION Multi-Strategy Cochlear Implant with the Continuous Interleaved Sampler (CIS) speech coding strategy. All were under 5 years old at implantation. Preimplantation, there were no significant differences between the groups in age, length of hearing aid use, or communication mode. Auditory skills were assessed at 6 months and 12 months after implantation. Postimplantation, the mean scores on all speech perception tests were higher for the Clarion group. These differences were statistically significant for the pattern perception and monosyllable subtests of the Early Speech Perception battery at 6 months, and for the Glendonald Auditory Screening Procedure at 12 months. Multiple regression analysis revealed that device type accounted for the greatest variance in performance after 12 months of implant use. We conclude that children using the CIS strategy implemented in the Clarion implant may develop better auditory perceptual skills during the first year postimplantation than children using the SPEAK strategy with the Nucleus device.
Frequency-specific corticofugal modulation of the dorsal cochlear nucleus in mice.

PubMed

Kong, Lingzhi; Xiong, Colin; Li, Liang; Yan, Jun

2014-01-01

The primary auditory cortex (AI) modulates the sound information processing in the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus (AVCN), in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a non-lemniscal subcortical nucleus but it is tonotopically organized like the AVCN. However, it remains unclear how the AI modulates the sound information processing in the DCN. This study examined the impact of focal electrical stimulation of AI on the auditory responses of the DCN neurons in mice. We found that the electrical stimulation induced significant changes in the best frequency (BF) of DCN neurons. The changes in the BFs were highly specific to the BF differences between the stimulated AI neurons and the recorded DCN neurons. The DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed no change when the AI and DCN BFs were similar. Moreover, the BF shifts were linearly correlated to the BF differences. Thus, our data suggest that corticofugal modulation of the DCN is also highly specific to frequency information, similar to the corticofugal modulation of the AVCN. The frequency-specificity of corticofugal modulation does not appear limited to the lemniscal ascending pathway.
Comparison of speech perception performance between Sprint/Esprit 3G and Freedom processors in children implanted with nucleus cochlear implants.

PubMed

Santarelli, Rosamaria; Magnavita, Vincenzo; De Filippi, Roberta; Ventura, Laura; Genovese, Elisabetta; Arslan, Edoardo

2009-04-01

To compare speech perception performance in children fitted with previous generation Nucleus sound processor, Sprint or Esprit 3G, and the Freedom, the most recently released system from the Cochlear Corporation that features a larger input dynamic range. Prospective intrasubject comparative study. University Medical Center. Seventeen prelingually deafened children who had received the Nucleus 24 cochlear implant and used the Sprint or Esprit 3G sound processor. Cochlear implantation with Cochlear device. Speech perception was evaluated at baseline (Sprint, n = 11; Esprit 3G, n = 6) and after 1 month's experience with the Freedom sound processor. Identification and recognition of disyllabic words and identification of vowels were performed via recorded voice in quiet (70 dB [A]), in the presence of background noise at various levels of signal-to-noise ratio (+10, +5, 0, -5) and at a soft presentation level (60 dB [A]). Consonant identification and recognition of disyllabic words, trisyllabic words, and sentences were evaluated in live voice. Frequency discrimination was measured in a subset of subjects (n = 5) by using an adaptive, 3-interval, 3-alternative, forced-choice procedure. Identification of disyllabic words administered at a soft presentation level showed a significant increase when switching to the Freedom compared with the previously worn processor in children using the Sprint or Esprit 3G. Identification and recognition of disyllabic words in the presence of background noise as well as consonant identification and sentence recognition increased significantly for the Freedom compared with the previously worn device only in children fitted with the Sprint. Frequency discrimination was significantly better when switching to the Freedom compared with the previously worn processor. Serial comparisons revealed that that speech perception performance evaluated in children aged 5 to 15 years was superior with the Freedom than previous generations of Nucleus sound processors. These differences are deemed to ensue from an increased input dynamic range, a feature that offers potentially enhanced phonemic discrimination.
Development of the mouse cochlea database (MCD).

PubMed

Santi, Peter A; Rapson, Ian; Voie, Arne

2008-09-01

The mouse cochlea database (MCD) provides an interactive, image database of the mouse cochlea for learning its anatomy and data mining of its resources. The MCD website is hosted on a centrally maintained, high-speed server at the following URL: (http://mousecochlea.umn.edu). The MCD contains two types of image resources, serial 2D image stacks and 3D reconstructions of cochlear structures. Complete image stacks of the cochlea from two different mouse strains were obtained using orthogonal plane fluorescence optical microscopy (OPFOS). 2D images of the cochlea are presented on the MCD website as: viewable images within a stack, 2D atlas of the cochlea, orthogonal sections, and direct volume renderings combined with isosurface reconstructions. In order to assess cochlear structures quantitatively, "true" cross-sections of the scala media along the length of the basilar membrane were generated by virtual resectioning of a cochlea orthogonal to a cochlear structure, such as the centroid of the basilar membrane or the scala media. 3D images are presented on the MCD website as: direct volume renderings, movies, interactive QuickTime VRs, flythrough, and isosurface 3D reconstructions of different cochlear structures. 3D computer models can also be used for solid model fabrication by rapid prototyping and models from different cochleas can be combined to produce an average 3D model. The MCD is the first comprehensive image resource on the mouse cochlea and is a new paradigm for understanding the anatomy of the cochlea, and establishing morphometric parameters of cochlear structures in normal and mutant mice.
Bidirectional synaptic plasticity in the cerebellum-like mammalian dorsal cochlear nucleus

NASA Astrophysics Data System (ADS)

Fujino, Kiyohiro; Oertel, Donata

2003-01-01

The dorsal cochlear nucleus integrates acoustic with multimodal sensory inputs from widespread areas of the brain. Multimodal inputs are brought to spiny dendrites of fusiform and cartwheel cells in the molecular layer by parallel fibers through synapses that are subject to long-term potentiation and long-term depression. Acoustic cues are brought to smooth dendrites of fusiform cells in the deep layer by auditory nerve fibers through synapses that do not show plasticity. Plasticity requires Ca2+-induced Ca2+ release; its sensitivity to antagonists of N-methyl-D-aspartate and metabotropic glutamate receptors differs in fusiform and cartwheel cells.
Modulation of Excitability of Stellate Neurons in the Ventral Cochlear Nucleus of Mice by ATP-Sensitive Potassium Channels.

PubMed

Bal, Ramazan; Ozturk, Gurkan; Etem, Ebru Onalan; Him, Aydin; Cengiz, Nurattin; Kuloglu, Tuncay; Tuzcu, Mehmet; Yildirim, Caner; Tektemur, Ahmet

2018-02-01

Major voltage-activated ionic channels of stellate cells in the ventral part of cochlear nucleus (CN) were largely characterized previously. However, it is not known if these cells are equipped with other ion channels apart from the voltage-sensitive ones. In the current study, it was aimed to study subunit composition and function of ATP-sensitive potassium channels (K ATP ) in stellate cells of the ventral cochlear nucleus. Subunits of K ATP channels, Kir6.1, Kir6.2, SUR1, and SUR2, were expressed at the mRNA level and at the protein level in the mouse VCN tissue. The specific and clearly visible bands for all subunits but that for Kir6.1 were seen in Western blot. Using immunohistochemical staining technique, stellate cells were strongly labeled with SUR1 and Kir6.2 antibodies and moderately labeled with SUR2 antibody, whereas the labeling signals for Kir6.1 were too weak. In patch clamp recordings, K ATP agonists including cromakalim (50 µM), diazoxide (0.2 mM), 3-Amino-1,2,4-triazole (ATZ) (1 mM), 2,2-Dithiobis (5-nitro pyridine) (DTNP) (330 µM), 6-Chloro-3-isopropylamino- 4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NNC 55-0118) (1 µM), 6-chloro-3-(methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NN414) (1 µM), and H 2 O 2 (0.88 mM) induced marked responses in stellate cells, characterized by membrane hyperpolarization which were blocked by K ATP antagonists. Blockers of K ATP channels, glibenclamide (0.2 mM), tolbutamide (0.1 mM) as well as 5-hydroxydecanoic acid (1 mM), and catalase (500 IU/ml) caused depolarization of stellate cells, increasing spontaneous action potential firing. In conclusion, K ATP channels seemed to be composed dominantly of Kir 6.2 subunit and SUR1 and SUR2 and activation or inhibition of K ATP channels regulates firing properties of stellate cells by means of influencing resting membrane potential and input resistance.
Multichannel cochlear implantation in the scala vestibuli.

PubMed

Lin, Karen; Marrinan, Michelle S; Waltzman, Susan B; Roland, J Thomas

2006-08-01

Sensorineural hearing loss resulting from otosclerosis, meningitis, chronic otitis media, autoimmune ear disease, and trauma can be associated with partial or total obstruction of the cochlear scalae. Multichannel cochlear implantation may be difficult in a cochlea with an obstructed scala tympani. The purpose of this study is to determine the safety and efficacy of scala tympani electrode insertion. Retrospective chart review. Academic medical center. Eight children and adults with profound sensorineural hearing loss who underwent cochlear implantation with known scala vestibuli electrode array insertion were subjects for this study. Eight study subjects underwent implantation: five with the Nucleus 24RCS (Contour) device and three with the Nucleus 24M device. Imaging findings, operative findings, and age-appropriate speech perception testing. All patients had full electrode insertion. Various obstructive patterns on computed tomography and magnetic resonance imaging were found, and there was a range of speech perception results. All but one patient improved based on age-appropriate monosyllabic word and sentence tests. Scala vestibuli multielectrode insertion is a viable alternative when scala tympani insertion is not possible because of abnormal anatomy or anatomical changes secondary to disease or previous implantation. We will also present an algorithm of options for decision making for implantation when encountering cochlear obstruction and difficult electrode insertion.
Retrograde transport of (/sup 3/H)-D-aspartate label by cochlear and vestibular efferent neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwarz, D.W.; Schwarz, I.E.

1988-01-01

(/sup 3/H)-D-aspartic acid was injected into the inner ear of rats. After a six hour survival time, labeled cells were found at all locations known to contain efferent cochlear or vestibular neurons. Most labeled neurons were found in the ipsilateral lateral superior olivary nucleus (LSO), although both ventral nuclei of the trapezoid body (VTB), group E, and the caudal pontine reticular nucleus (CPR) just adjacent to the ascending limb of the facial nerve also contained labeled cells. Because not all efferent neurons in the rat could be previously shown to be cholinergic, aspartate and glutamate are efferent transmitter candidates.
Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus

PubMed Central

Kurioka, Takaomi; Lee, Min Young; Heeringa, Amarins N.; Beyer, Lisa A.; Swiderski, Donald L.; Kanicki, Ariane C.; Kabara, Lisa L.; Dolan, David F.; Shore, Susan E.; Raphael, Yehoash

2016-01-01

In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus. However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). We showed that DT-induced HC ablation has no significant impacts on the survival of auditory neurons, central synaptic terminals, and myelin, despite complete HC loss and profound deafness. In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and cochlear nucleus neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination. PMID:27403879
Assembly of the Auditory Circuitry by a Hox Genetic Network in the Mouse Brainstem

PubMed Central

Di Bonito, Maria; Narita, Yuichi; Avallone, Bice; Sequino, Luigi; Mancuso, Marta; Andolfi, Gennaro; Franzè, Anna Maria; Puelles, Luis; Rijli, Filippo M.; Studer, Michèle

2013-01-01

Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem. PMID:23408898
Assembly of the auditory circuitry by a Hox genetic network in the mouse brainstem.

PubMed

Di Bonito, Maria; Narita, Yuichi; Avallone, Bice; Sequino, Luigi; Mancuso, Marta; Andolfi, Gennaro; Franzè, Anna Maria; Puelles, Luis; Rijli, Filippo M; Studer, Michèle

2013-01-01

Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem.
Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium.

PubMed

Chen, Yan; Li, Wenyan; Li, Wen; Chai, Renjie; Li, Huawei

2016-09-01

The enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) is a histone-lysine Nmethyltransferase enzyme that participates in DNA methylation. Ezh2 has also been reported to play crucial roles in stem cell proliferation and differentiation. However, the detailed expression profile of Ezh2 during mouse cochlear development has not been investigated. Here, we examined the spatiotemporal expression of Ezh2 in the cochlea during embryonic and postnatal development. Ezh2 expression began to be observed in the whole otocyst nuclei at embryonic day 9.5 (E9.5). At E12.5, Ezh2 was expressed in the nuclei of the cochlear prosensory epithelium. At E13.5 and E15.5, Ezh2 was expressed from the apical to the basal turns in the nuclei of the differentiating cochlear epithelium. At postnatal day (P) 0 and 7, the Ezh2 expression was located in the nuclei of the cochlear epithelium in all three turns and could be clearly seen in outer and inner hair cells, supporting cells, the stria vascularis, and spiral ganglion cells. Ezh2 continued to be expressed in the cochlear epithelium of adult mice. Our results provide the basic Ezh2 expression pattern and might be useful for further investigating the detailed role of Ezh2 during cochlear development.
Partial corrosion casting to assess cochlear vasculature in mouse models of presbycusis and CMV infection.

PubMed

Carraro, Mattia; Park, Albert H; Harrison, Robert V

2016-02-01

Some forms of sensorineural hearing loss involve damage or degenerative changes to the stria vascularis and/or other vascular structures in the cochlea. In animal models, many methods for anatomical assessment of cochlear vasculature exist, each with advantages and limitations. One methodology, corrosion casting, has proved useful in some species, however in the mouse model this technique is difficult to achieve because digestion of non vascular tissue results in collapse of the delicate cast specimen. We have developed a partial corrosion cast method that allows visualization of vasculature along much of the cochlear length but maintains some structural integrity of the specimen. We provide a detailed step-by-step description of this novel technique. We give some illustrative examples of the use of the method in mouse models of presbycusis and cytomegalovirus (CMV) infection. Copyright © 2015 Elsevier B.V. All rights reserved.
A biophysical model for modulation frequency encoding in the cochlear nucleus.

PubMed

Eguia, Manuel C; Garcia, Guadalupe C; Romano, Sebastian A

2010-01-01

Encoding of amplitude modulated (AM) acoustical signals is one of the most compelling tasks for the mammalian auditory system: environmental sounds, after being filtered and transduced by the cochlea, become narrowband AM signals. Despite much experimental work dedicated to the comprehension of auditory system extraction and encoding of AM information, the neural mechanisms underlying this remarkable feature are far from being understood (Joris et al., 2004). One of the most accepted theories for this processing is the existence of a periodotopic organization (based on temporal information) across the more studied tonotopic axis (Frisina et al., 1990b). In this work, we will review some recent advances in the study of the mechanisms involved in neural processing of AM sounds, and propose an integrated model that runs from the external ear, through the cochlea and the auditory nerve, up to a sub-circuit of the cochlear nucleus (the first processing unit in the central auditory system). We will show that varying the amount of inhibition in our model we can obtain a range of best modulation frequencies (BMF) in some principal cells of the cochlear nucleus. This could be a basis for a synchronicity based, low-level periodotopic organization. Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Monitoring blood-flow in the mouse cochlea using an endoscopic laser speckle contrast imaging system

PubMed Central

Yu, Sunkon; Jung, Byungjo; Choi, Jin Sil

2018-01-01

Laser speckle contrast imaging (LSCI) enables continuous high-resolution assessment of microcirculation in real-time. We applied an endoscope to LSCI to measure cochlear blood-flow in an ischemia–reperfusion mouse model. We also explored whether using xenon light in combination with LSCI facilitates visualization of anatomical position. Based on a previous preliminary study, the appropriate wavelength for penetrating the thin bony cochlea was 830 nm. A 2.7-mm-diameter endoscope was used, as appropriate for the size of the mouse cochlea. Our endoscopic LSCI system was used to illuminate the right cochlea after dissection of the mouse. We observed changes in the speckle signals when we applied the endoscopic LSCI system to the ischemia-reperfusion mouse model. The anatomical structure of the mouse cochlea and surrounding structures were clearly visible using the xenon light. The speckle signal of the cochlea was scattered, with an intensity that varied between that of the stapes (with the lowest signal), the negative control, and the stapedial artery (with the highest signal), the positive control. In the cochlear ischemia–reperfusion mouse model, the speckle signal of the cochlea decreased during the ischemic phase, and increased during the reperfusion phase, clearly reflecting cochlear blood-flow. The endoscopic LSCI system generates high-resolution images in real-time, allowing visualization of blood-flow and its changes in the mouse cochlea. Anatomical structures were clearly matched using LSCI along with visible light. PMID:29489849
Monitoring blood-flow in the mouse cochlea using an endoscopic laser speckle contrast imaging system.

PubMed

Kong, Tae Hoon; Yu, Sunkon; Jung, Byungjo; Choi, Jin Sil; Seo, Young Joon

2018-01-01

Laser speckle contrast imaging (LSCI) enables continuous high-resolution assessment of microcirculation in real-time. We applied an endoscope to LSCI to measure cochlear blood-flow in an ischemia-reperfusion mouse model. We also explored whether using xenon light in combination with LSCI facilitates visualization of anatomical position. Based on a previous preliminary study, the appropriate wavelength for penetrating the thin bony cochlea was 830 nm. A 2.7-mm-diameter endoscope was used, as appropriate for the size of the mouse cochlea. Our endoscopic LSCI system was used to illuminate the right cochlea after dissection of the mouse. We observed changes in the speckle signals when we applied the endoscopic LSCI system to the ischemia-reperfusion mouse model. The anatomical structure of the mouse cochlea and surrounding structures were clearly visible using the xenon light. The speckle signal of the cochlea was scattered, with an intensity that varied between that of the stapes (with the lowest signal), the negative control, and the stapedial artery (with the highest signal), the positive control. In the cochlear ischemia-reperfusion mouse model, the speckle signal of the cochlea decreased during the ischemic phase, and increased during the reperfusion phase, clearly reflecting cochlear blood-flow. The endoscopic LSCI system generates high-resolution images in real-time, allowing visualization of blood-flow and its changes in the mouse cochlea. Anatomical structures were clearly matched using LSCI along with visible light.

Improving speech perception in noise for children with cochlear implants.

PubMed

Gifford, René H; Olund, Amy P; Dejong, Melissa

2011-10-01

Current cochlear implant recipients are achieving increasingly higher levels of speech recognition; however, the presence of background noise continues to significantly degrade speech understanding for even the best performers. Newer generation Nucleus cochlear implant sound processors can be programmed with SmartSound strategies that have been shown to improve speech understanding in noise for adult cochlear implant recipients. The applicability of these strategies for use in children, however, is not fully understood nor widely accepted. To assess speech perception for pediatric cochlear implant recipients in the presence of a realistic restaurant simulation generated by an eight-loudspeaker (R-SPACE™) array in order to determine whether Nucleus sound processor SmartSound strategies yield improved sentence recognition in noise for children who learn language through the implant. Single subject, repeated measures design. Twenty-two experimental subjects with cochlear implants (mean age 11.1 yr) and 25 control subjects with normal hearing (mean age 9.6 yr) participated in this prospective study. Speech reception thresholds (SRT) in semidiffuse restaurant noise originating from an eight-loudspeaker array were assessed with the experimental subjects' everyday program incorporating Adaptive Dynamic Range Optimization (ADRO) as well as with the addition of Autosensitivity control (ASC). Adaptive SRTs with the Hearing In Noise Test (HINT) sentences were obtained for all 22 experimental subjects, and performance-in percent correct-was assessed in a fixed +6 dB SNR (signal-to-noise ratio) for a six-subject subset. Statistical analysis using a repeated-measures analysis of variance (ANOVA) evaluated the effects of the SmartSound setting on the SRT in noise. The primary findings mirrored those reported previously with adult cochlear implant recipients in that the addition of ASC to ADRO significantly improved speech recognition in noise for pediatric cochlear implant recipients. The mean degree of improvement in the SRT with the addition of ASC to ADRO was 3.5 dB for a mean SRT of 10.9 dB SNR. Thus, despite the fact that these children have acquired auditory/oral speech and language through the use of their cochlear implant(s) equipped with ADRO, the addition of ASC significantly improved their ability to recognize speech in high levels of diffuse background noise. The mean SRT for the control subjects with normal hearing was 0.0 dB SNR. Given that the mean SRT for the experimental group was 10.9 dB SNR, despite the improvements in performance observed with the addition of ASC, cochlear implants still do not completely overcome the speech perception deficit encountered in noisy environments accompanying the diagnosis of severe-to-profound hearing loss. SmartSound strategies currently available in latest generation Nucleus cochlear implant sound processors are able to significantly improve speech understanding in a realistic, semidiffuse noise for pediatric cochlear implant recipients. Despite the reluctance of pediatric audiologists to utilize SmartSound settings for regular use, the results of the current study support the addition of ASC to ADRO for everyday listening environments to improve speech perception in a child's typical everyday program. American Academy of Audiology.
Modeling open-set spoken word recognition in postlingually deafened adults after cochlear implantation: some preliminary results with the neighborhood activation model.

PubMed

Meyer, Ted A; Frisch, Stefan A; Pisoni, David B; Miyamoto, Richard T; Svirsky, Mario A

2003-07-01

Do cochlear implants provide enough information to allow adult cochlear implant users to understand words in ways that are similar to listeners with acoustic hearing? Can we use a computational model to gain insight into the underlying mechanisms used by cochlear implant users to recognize spoken words? The Neighborhood Activation Model has been shown to be a reasonable model of word recognition for listeners with normal hearing. The Neighborhood Activation Model assumes that words are recognized in relation to other similar-sounding words in a listener's lexicon. The probability of correctly identifying a word is based on the phoneme perception probabilities from a listener's closed-set consonant and vowel confusion matrices modified by the relative frequency of occurrence of the target word compared with similar-sounding words (neighbors). Common words with few similar-sounding neighbors are more likely to be selected as responses than less common words with many similar-sounding neighbors. Recent studies have shown that several of the assumptions of the Neighborhood Activation Model also hold true for cochlear implant users. Closed-set consonant and vowel confusion matrices were obtained from 26 postlingually deafened adults who use cochlear implants. Confusion matrices were used to represent input errors to the Neighborhood Activation Model. Responses to the different stimuli were then generated by the Neighborhood Activation Model after incorporating the frequency of occurrence counts of the stimuli and their neighbors. Model outputs were compared with obtained performance measures on the Consonant-Vowel Nucleus-Consonant word test. Information transmission analysis was used to assess whether the Neighborhood Activation Model was able to successfully generate and predict word and individual phoneme recognition by cochlear implant users. The Neighborhood Activation Model predicted Consonant-Vowel Nucleus-Consonant test words at levels similar to those correctly identified by the cochlear implant users. The Neighborhood Activation Model also predicted phoneme feature information well. The results obtained suggest that the Neighborhood Activation Model provides a reasonable explanation of word recognition by postlingually deafened adults after cochlear implantation. It appears that multichannel cochlear implants give cochlear implant users access to their mental lexicons in a manner that is similar to listeners with acoustic hearing. The lexical properties of the test stimuli used to assess performance are important to spoken-word recognition and should be included in further models of the word recognition process.
Type 2 iodothyronine deiodinase expression in the cochlea before the onset of hearing

PubMed Central

Campos-Barros, Angel; Amma, Lori L.; Faris, Jonathan S.; Shailam, Ranu; Kelley, Matthew W.; Forrest, Douglas

2000-01-01

Thyroid hormone signaling during a postnatal period in the mouse is essential for cochlear development and the subsequent onset of hearing. To study the control of this temporal dependency, we investigated the role of iodothyronine deiodinases, which in target tissues convert the prohormone thyroxine into triiodothyronine (T3), the active ligand for the thyroid hormone receptor (TR). Type 2 5′-deiodinase (D2) activity rose dramatically in the mouse cochlea to peak around postnatal day 7 (P7), after which activity declined by P10. This activity peak a few days before the onset of hearing suggests a role for D2 in amplifying local T3 levels at a critical stage of cochlear development. A mouse cochlear D2 cDNA was isolated and demonstrated near identity to rat D2. In situ hybridization localized D2 mRNA in periosteal connective tissue in the modiolus, the cochlear outer capsule and the septal divisions between the turns of the cochlea. Surprisingly, D2 expression in these regions that give rise to the bony labyrinth was complementary to TR expression in the sensory epithelium. Thus, the connective tissue may control deiodination of thyroxine and release of T3 to confer a paracrine-like control of TR activation. These results suggest that temporal and spatial control of ligand availability conferred by D2 provides an unexpectedly important level of regulation of the TR pathways required for cochlear maturation. PMID:10655523
Reticular lamina and basilar membrane vibrations in the basal turn of gerbil and mouse cochleae

NASA Astrophysics Data System (ADS)

Ren, Tianying; He, Wenxuan

2018-05-01

Low-coherence interferometry in living cochleae has provided valuable information for understanding cochlear micromechanics. A recent measurement of the reticular lamina and basilar membrane vibrations in mouse cochleae, however, is inconsistent with data collected from guinea pig cochleae. To determine whether a species difference accounts for the observed difference, a custom-built heterodyne low-coherence interferometer was used to measure reticular lamina and basilar membrane vibrations at the basal turn of sensitive gerbil and mouse cochleae. For the gerbil and mouse, both the reticular lamina and basilar membrane vibrations show sharp tuning and nonlinear compressive growth near the best frequency. The magnitude of the reticular lamina vibration is significantly greater than that of the basilar membrane vibration not only near the best frequency, but also at low frequencies. The phase of the reticular lamina vibration leads the basilar membrane phase by up to 180-degrees at low frequencies, and this phase lead decreases with frequency, approaching zero near the best frequency. The best frequency of the reticular lamina and basilar membrane vibrations at the cochlear basal turn in mice is significantly higher than that in gerbils. Besides this difference, cochlear micromechanical responses in the gerbil are similar to those in the mouse. Thus, the current results indicate that gerbil and mouse cochleae detect and process sounds likely through a similar micromechanical mechanism.
Deep brain stimulation with a pre-existing cochlear implant: Surgical technique and outcome.

PubMed

Eddelman, Daniel; Wewel, Joshua; Wiet, R Mark; Metman, Leo V; Sani, Sepehr

2017-01-01

Patients with previously implanted cranial devices pose a special challenge in deep brain stimulation (DBS) surgery. We report the implantation of bilateral DBS leads in a patient with a cochlear implant. Technical nuances and long-term interdevice functionality are presented. A 70-year-old patient with advancing Parkinson's disease and a previously placed cochlear implant for sensorineural hearing loss was referred for placement of bilateral DBS in the subthalamic nucleus (STN). Prior to DBS, the patient underwent surgical removal of the subgaleal cochlear magnet, followed by stereotactic MRI, frame placement, stereotactic computed tomography (CT), and merging of imaging studies. This technique allowed for successful computational merging, MRI-guided targeting, and lead implantation with acceptable accuracy. Formal testing and programming of both the devices were successful without electrical interference. Successful DBS implantation with high resolution MRI-guided targeting is technically feasible in patients with previously implanted cochlear implants by following proper precautions.
Effects of Nicotine and Ethanol on Indices of Reward and Sensory-Motor Function in Rats: Implications for the Positive Epidemiologic Relationship Between the Use of Cigarettes and the Use of Alcohol

DTIC Science & Technology

1997-10-07

include the auditory nerve, the ventral cochlear nucleus , nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, spinal neuron, and lower...chambers. In addition, there was a significant effect of nicotine and ethanol to reduce the ratio of dopamine/DOPAC in nucleus accumbens. Because...dopaminergic activity in nucleus accumbens is known to mediate nicotine reinforcement, reductions in the ratio of dopamine/DOPAC (perhaps indicating an
Noise over-exposure alters long-term somatosensory-auditory processing in the dorsal cochlear nucleus – possible basis for tinnitus-related hyperactivity?

PubMed Central

Dehmel, Susanne; Pradhan, Shashwati; Koehler, Seth; Bledsoe, Sanford; Shore, Susan

2012-01-01

The dorsal cochlear nucleus (DCN) is the first neural site of bimodal auditory-somatosensory integration. Previous studies have shown that stimulation of somatosensory pathways results in immediate suppression or enhancement of subsequent acoustically-evoked discharges. In the unimpaired auditory system suppression predominates. However, damage to the auditory input pathway leads to enhancement of excitatory somatosensory inputs to the cochlear nucleus, changing their effects on DCN neurons (Zeng et al., 2009; Shore et al., 2008). Given the well described connection between the somatosensory system and tinnitus in patients we sought to determine if plastic changes in long lasting bimodal somatosensory-auditory processing accompany tinnitus. Here we demonstrate for the first time in vivo long-term effects of somatosensory inputs on acoustically-evoked discharges of DCN neurons in guinea pigs. The effects of trigeminal nucleus stimulation are compared between normal-hearing animals and animals overexposed with narrow band noise and behaviorally tested for tinnitus. The noise exposure resulted in a temporary threshold shift (TTS) in auditory brainstem responses but a persistent increase in spontaneous and sound-evoked DCN unit firing rates and increased steepness of rate-level functions (RLFs). Rate increases were especially prominent in buildup units. The long-term somatosensory enhancement of sound-evoked responses was strengthened while suppressive effects diminished in noise-exposed animals, especially those that developed tinnitus. Damage to the auditory nerve (ANF) is postulated to trigger compensatory long-term synaptic plasticity of somatosensory inputs that might be an important underlying mechanism for tinnitus generation. PMID:22302808
Dual Coding of Frequency Modulation in the Ventral Cochlear Nucleus.

PubMed

Paraouty, Nihaad; Stasiak, Arkadiusz; Lorenzi, Christian; Varnet, Léo; Winter, Ian M

2018-04-25

Frequency modulation (FM) is a common acoustic feature of natural sounds and is known to play a role in robust sound source recognition. Auditory neurons show precise stimulus-synchronized discharge patterns that may be used for the representation of low-rate FM. However, it remains unclear whether this representation is based on synchronization to slow temporal envelope (ENV) cues resulting from cochlear filtering or phase locking to faster temporal fine structure (TFS) cues. To investigate the plausibility of those encoding schemes, single units of the ventral cochlear nucleus of guinea pigs of either sex were recorded in response to sine FM tones centered at the unit's best frequency (BF). The results show that, in contrast to high-BF units, for modulation depths within the receptive field, low-BF units (<4 kHz) demonstrate good phase locking to TFS. For modulation depths extending beyond the receptive field, the discharge patterns follow the ENV and fluctuate at the modulation rate. The receptive field proved to be a good predictor of the ENV responses for most primary-like and chopper units. The current in vivo data also reveal a high level of diversity in responses across unit types. TFS cues are mainly conveyed by low-frequency and primary-like units and ENV cues by chopper and onset units. The diversity of responses exhibited by cochlear nucleus neurons provides a neural basis for a dual-coding scheme of FM in the brainstem based on both ENV and TFS cues. SIGNIFICANCE STATEMENT Natural sounds, including speech, convey informative temporal modulations in frequency. Understanding how the auditory system represents those frequency modulations (FM) has important implications as robust sound source recognition depends crucially on the reception of low-rate FM cues. Here, we recorded 115 single-unit responses from the ventral cochlear nucleus in response to FM and provide the first physiological evidence of a dual-coding mechanism of FM via synchronization to temporal envelope cues and phase locking to temporal fine structure cues. We also demonstrate a diversity of neural responses with different coding specializations. These results support the dual-coding scheme proposed by psychophysicists to account for FM sensitivity in humans and provide new insights on how this might be implemented in the early stages of the auditory pathway. Copyright © 2018 the authors 0270-6474/18/384123-15$15.00/0.
Should children who use cochlear implants wear hearing aids in the opposite ear?

PubMed

Ching, T Y; Psarros, C; Hill, M; Dillon, H; Incerti, P

2001-10-01

The aim of this study was to investigate 1) whether a hearing aid needs to be adjusted differently depending on whether a child wears a cochlear implant or another hearing aid in the contralateral ear; 2) whether the use of a hearing aid and a cochlear implant in opposite ears leads to binaural interference; and 3) whether the use of a hearing aid and a cochlear implant in opposite ears leads to binaural benefits in speech perception, localization, and communicative functioning in real life. Sixteen children participated in this study. All children used a Nucleus 22 or Nucleus 24 cochlear implant system programmed with the SPEAK strategy in one ear. The hearing aid amplification requirements in the nonimplanted ear of these children were determined using two procedures. A paired comparison technique was used to identify the frequency response that was best for speech intelligibility in quiet, and a loudness balancing technique was used to match the loudness of speech in the ear with a hearing aid to that with a cochlear implant. Eleven of the 16 children participated in the investigation of binaural effects. Performance in speech perception, localization, and communicative functioning was assessed under four aided conditions: cochlear implant with hearing aid as worn, cochlear implant alone, hearing aid alone, and cochlear implant with hearing aid adjusted according to individual requirements. Fifteen of the 16 children whose amplification requirements were determined preferred a hearing aid frequency response that was within +/-6 dB/octave of the NAL-RP prescription. On average, the children required 6 dB more gain than prescribed to balance the loudness of the implanted ear for a speech signal presented at 65 dB SPL. For all 11 children whose performance was evaluated for investigating binaural effects, there was no indication of significantly poorer performance under bilaterally aided conditions compared with unilaterally aided conditions. On average, there were significant benefits in speech perception, localization, and aural/oral function when the children used cochlear implants with adjusted hearing aids than when they used cochlear implants alone. All individuals showed benefits in at least one of the measures. Hearing aids for children who also use cochlear implants can be selected using the NAL-RP prescription. Adjustment of hearing aid gain to match loudness in the implanted ear can facilitate integration of signals from both ears, leading to better speech perception. Given that there are binaural advantages from using cochlear implants with hearing aids in opposite ears, clinicians should advise parents and other professionals about these potential advantages, and facilitate bilateral amplification by adjusting hearing aids after stable cochlear implant MAPs are established.
Sound-direction identification with bilateral cochlear implants.

PubMed

Neuman, Arlene C; Haravon, Anita; Sislian, Nicole; Waltzman, Susan B

2007-02-01

The purpose of this study was to compare the accuracy of sound-direction identification in the horizontal plane by bilateral cochlear implant users when localization was measured with pink noise and with speech stimuli. Eight adults who were bilateral users of Nucleus 24 Contour devices participated in the study. All had received implants in both ears in a single surgery. Sound-direction identification was measured in a large classroom by using a nine-loudspeaker array. Localization was tested in three listening conditions (bilateral cochlear implants, left cochlear implant, and right cochlear implant), using two different stimuli (a speech stimulus and pink noise bursts) in a repeated-measures design. Sound-direction identification accuracy was significantly better when using two implants than when using a single implant. The mean root-mean-square error was 29 degrees for the bilateral condition, 54 degrees for the left cochlear implant, and 46.5 degrees for the right cochlear implant condition. Unilateral accuracy was similar for right cochlear implant and left cochlear implant performance. Sound-direction identification performance was similar for speech and pink noise stimuli. The data obtained in this study add to the growing body of evidence that sound-direction identification with bilateral cochlear implants is better than with a single implant. The similarity in localization performance obtained with the speech and pink noise supports the use of either stimulus for measuring sound-direction identification.
Result on speech perception after conversion from Spectra® to Freedom®.

PubMed

Magalhães, Ana Tereza de Matos; Goffi-Gomez, Maria Valéria Schmidt; Hoshino, Ana Cristina; Tsuji, Robinson Koji; Bento, Ricardo Ferreira; Brito, Rubens

2012-04-01

New technology in the Freedom® speech processor for cochlear implants was developed to improve how incoming acoustic sound is processed; this applies not only for new users, but also for previous generations of cochlear implants. To identify the contribution of this technology-- the Nucleus 22®--on speech perception tests in silence and in noise, and on audiometric thresholds. A cross-sectional cohort study was undertaken. Seventeen patients were selected. The last map based on the Spectra® was revised and optimized before starting the tests. Troubleshooting was used to identify malfunction. To identify the contribution of the Freedom® technology for the Nucleus22®, auditory thresholds and speech perception tests were performed in free field in sound-proof booths. Recorded monosyllables and sentences in silence and in noise (SNR = 0dB) were presented at 60 dBSPL. The nonparametric Wilcoxon test for paired data was used to compare groups. Freedom® applied for the Nucleus22® showed a statistically significant difference in all speech perception tests and audiometric thresholds. The Freedom® technology improved the performance of speech perception and audiometric thresholds of patients with Nucleus 22®.
Modeling Open-Set Spoken Word Recognition in Postlingually Deafened Adults after Cochlear Implantation: Some Preliminary Results with the Neighborhood Activation Model

PubMed Central

Meyer, Ted A.; Frisch, Stefan A.; Pisoni, David B.; Miyamoto, Richard T.; Svirsky, Mario A.

2012-01-01

Hypotheses Do cochlear implants provide enough information to allow adult cochlear implant users to understand words in ways that are similar to listeners with acoustic hearing? Can we use a computational model to gain insight into the underlying mechanisms used by cochlear implant users to recognize spoken words? Background The Neighborhood Activation Model has been shown to be a reasonable model of word recognition for listeners with normal hearing. The Neighborhood Activation Model assumes that words are recognized in relation to other similar-sounding words in a listener’s lexicon. The probability of correctly identifying a word is based on the phoneme perception probabilities from a listener’s closed-set consonant and vowel confusion matrices modified by the relative frequency of occurrence of the target word compared with similar-sounding words (neighbors). Common words with few similar-sounding neighbors are more likely to be selected as responses than less common words with many similar-sounding neighbors. Recent studies have shown that several of the assumptions of the Neighborhood Activation Model also hold true for cochlear implant users. Methods Closed-set consonant and vowel confusion matrices were obtained from 26 postlingually deafened adults who use cochlear implants. Confusion matrices were used to represent input errors to the Neighborhood Activation Model. Responses to the different stimuli were then generated by the Neighborhood Activation Model after incorporating the frequency of occurrence counts of the stimuli and their neighbors. Model outputs were compared with obtained performance measures on the Consonant-Vowel Nucleus-Consonant word test. Information transmission analysis was used to assess whether the Neighborhood Activation Model was able to successfully generate and predict word and individual phoneme recognition by cochlear implant users. Results The Neighborhood Activation Model predicted Consonant-Vowel Nucleus-Consonant test words at levels similar to those correctly identified by the cochlear implant users. The Neighborhood Activation Model also predicted phoneme feature information well. Conclusion The results obtained suggest that the Neighborhood Activation Model provides a reasonable explanation of word recognition by postlingually deafened adults after cochlear implantation. It appears that multichannel cochlear implants give cochlear implant users access to their mental lexicons in a manner that is similar to listeners with acoustic hearing. The lexical properties of the test stimuli used to assess performance are important to spoken-word recognition and should be included in further models of the word recognition process. PMID:12851554
Swept-sine noise-induced damage as a hearing loss model for preclinical assays

PubMed Central

Sanz, Lorena; Murillo-Cuesta, Silvia; Cobo, Pedro; Cediel-Algovia, Rafael; Contreras, Julio; Rivera, Teresa; Varela-Nieto, Isabel; Avendaño, Carlos

2015-01-01

Mouse models are key tools for studying cochlear alterations in noise-induced hearing loss (NIHL) and for evaluating new therapies. Stimuli used to induce deafness in mice are usually white and octave band noises that include very low frequencies, considering the large mouse auditory range. We designed different sound stimuli, enriched in frequencies up to 20 kHz (“violet” noises) to examine their impact on hearing thresholds and cochlear cytoarchitecture after short exposure. In addition, we developed a cytocochleogram to quantitatively assess the ensuing structural degeneration and its functional correlation. Finally, we used this mouse model and cochleogram procedure to evaluate the potential therapeutic effect of transforming growth factor β1 (TGF-β1) inhibitors P17 and P144 on NIHL. CBA mice were exposed to violet swept-sine noise (VS) with different frequency ranges (2–20 or 9–13 kHz) and levels (105 or 120 dB SPL) for 30 min. Mice were evaluated by auditory brainstem response (ABR) and otoacoustic emission tests prior to and 2, 14 and 28 days after noise exposure. Cochlear pathology was assessed with gross histology; hair cell number was estimated by a stereological counting method. Our results indicate that functional and morphological changes induced by VS depend on the sound level and frequency composition. Partial hearing recovery followed the exposure to 105 dB SPL, whereas permanent cochlear damage resulted from the exposure to 120 dB SPL. Exposure to 9–13 kHz noise caused an auditory threshold shift (TS) in those frequencies that correlated with hair cell loss in the corresponding areas of the cochlea that were spotted on the cytocochleogram. In summary, we present mouse models of NIHL, which depending on the sound properties of the noise, cause different degrees of cochlear damage, and could therefore be used to study molecules which are potential players in hearing loss protection and repair. PMID:25762930
The arcuate nucleus of the C57BL/6J mouse hindbrain is a displaced part of the inferior olive.

PubMed

Fu, Yu Hong; Watson, Charles

2012-01-01

The arcuate nucleus is a prominent cell group in the human hindbrain, characterized by its position on the pial surface of the pyramid. It is considered to be a precerebellar nucleus and has been implicated in the pathology of several disorders of respiration. An arcuate nucleus has not been convincingly demonstrated in other mammals, but we have found a similarly positioned nucleus in the C57BL/6J mouse. The mouse arcuate nucleus consists of a variable group of neurons lying on the pial surface of the pyramid. The nucleus is continuous with the ventrolateral part of the principal nucleus of the inferior olive and both groups are calbindin positive. At first we thought that this mouse nucleus was homologous with the human arcuate nucleus, but we have discovered that the neurons of the human nucleus are calbindin negative, and are therefore not olivary in nature. We have compared the mouse arcuate neurons with those of the inferior olive in terms of molecular markers and cerebellar projection. The neurons of the arcuate nucleus and of the inferior olive share three major characteristics: they both contain neurons utilizing glutamate, serotonin or acetylcholine as neurotransmitters; they both project to the contralateral cerebellum, and they both express a number of genes not present in the major mossy fiber issuing precerebellar nuclei. Most importantly, both cell groups express calbindin in an area of the ventral hindbrain almost completely devoid of calbindin-positive cells. We conclude that the neurons of the hindbrain mouse arcuate nucleus are a displaced part of the inferior olive, possibly separated by the caudal growth of the pyramidal tract during development. The arcuate nucleus reported in the C57BL/6J mouse can therefore be regarded as a subgroup of the rostral inferior olive, closely allied with the ventral tier of the principal nucleus. Copyright © 2012 S. Karger AG, Basel.
Origins of Glutamatergic Terminals in the Inferior Colliculus Identified by Retrograde Transport and Expression of VGLUT1 and VGLUT2 Genes.

PubMed

Ito, Tetsufumi; Oliver, Douglas L

2010-01-01

Terminals containing vesicular glutamate transporter (VGLUT) 2 make dense axosomatic synapses on tectothalamic GABAergic neurons. These are one of the three types of glutamatergic synapses in the inferior colliculus (IC) identified by one of three combinations of transporter protein: VGLUT1 only, VGLUT2 only, or both VGLUT1 and 2. To identify the source(s) of these three classes of glutamatergic terminals, we employed the injection of Fluorogold (FG) into the IC and retrograde transport in combination with in situ hybridization for VGLUT1 and VGLUT2 mRNA. The distribution of FG-positive soma was consistent with previous reports. In the auditory cortex, all FG-positive cells expressed only VGLUT1. In the IC, the majority of FG-positive cells expressed only VGLUT2. In the intermediate nucleus of the lateral lemniscus, most FG-positive cells expressed VGLUT2, and a few FG-positive cells expressed both VGLUT1 and 2. In the superior olivary complex (SOC), the majority of FG-positive cells expressing VGLUT2 were in the lateral superior olive, medial superior olive, and some periolivary nuclei. Fewer FG-positive cells expressed VGLUT1&2. In the ventral cochlear nucleus, almost all FG-positive cells expressed VGLUT1&2. On the other hand in the dorsal cochlear nucleus, the vast majority of FG-positive cells expressed only VGLUT2. Our data suggest that (1) the most likely sources of VGLUT2 terminals in the IC are the intermediate nucleus of the lateral lemniscus, the dorsal cochlear nucleus, the medial and lateral superior olive, and the IC itself, (2) VGLUT1 terminals in the IC originate only in the ipsilateral auditory cortex, and (3) VGLUT1&2 terminals in IC originate mainly from the VCN with minor contributions from the SOC and the lateral lemniscal nuclei.
Corticofugal modulation of peripheral auditory responses

PubMed Central

Terreros, Gonzalo; Delano, Paul H.

2015-01-01

The auditory efferent system originates in the auditory cortex and projects to the medial geniculate body (MGB), inferior colliculus (IC), cochlear nucleus (CN) and superior olivary complex (SOC) reaching the cochlea through olivocochlear (OC) fibers. This unique neuronal network is organized in several afferent-efferent feedback loops including: the (i) colliculo-thalamic-cortico-collicular; (ii) cortico-(collicular)-OC; and (iii) cortico-(collicular)-CN pathways. Recent experiments demonstrate that blocking ongoing auditory-cortex activity with pharmacological and physical methods modulates the amplitude of cochlear potentials. In addition, auditory-cortex microstimulation independently modulates cochlear sensitivity and the strength of the OC reflex. In this mini-review, anatomical and physiological evidence supporting the presence of a functional efferent network from the auditory cortex to the cochlear receptor is presented. Special emphasis is given to the corticofugal effects on initial auditory processing, that is, on CN, auditory nerve and cochlear responses. A working model of three parallel pathways from the auditory cortex to the cochlea and auditory nerve is proposed. PMID:26483647
A software tool for analyzing multichannel cochlear implant signals.

PubMed

Lai, Wai Kong; Bögli, Hans; Dillier, Norbert

2003-10-01

A useful and convenient means to analyze the radio frequency (RF) signals being sent by a speech processor to a cochlear implant would be to actually capture and display them with appropriate software. This is particularly useful for development or diagnostic purposes. sCILab (Swiss Cochlear Implant Laboratory) is such a PC-based software tool intended for the Nucleus family of Multichannel Cochlear Implants. Its graphical user interface provides a convenient and intuitive means for visualizing and analyzing the signals encoding speech information. Both numerical and graphic displays are available for detailed examination of the captured CI signals, as well as an acoustic simulation of these CI signals. sCILab has been used in the design and verification of new speech coding strategies, and has also been applied as an analytical tool in studies of how different parameter settings of existing speech coding strategies affect speech perception. As a diagnostic tool, it is also useful for troubleshooting problems with the external equipment of the cochlear implant systems.
[The role of the cervical spine and the craniomandibular system in the pathogenesis of tinnitus. Somatosensory tinnitus].

PubMed

Biesinger, E; Reisshauer, A; Mazurek, B

2008-07-01

The causes of tinnitus, vertigo, and hearing disturbances may be pathological processes in the cervical spine and temporomaxillary joint. In these cases, tinnitus is called somatosensory tinnitus (SST). For afferences of the cervical spine, projections of neuronal connections in the cochlear nucleus were found. A reflex-like impact of the cervical spine on the cochlear nucleus can be assumed. The tinnitus treatment concept of the Charité University Hospital in Berlin involves the cooperation of ENT specialists with many other disciplines in an outpatient clinic. A standardized examination protocol has been established, and physical therapy has been integrated into the interdisciplinary tinnitus treatment. For tinnitus-modulating therapy of muscular trigger points, local anesthetics as well as self-massage or treatment by a physiotherapist or osteopath are useful.
Multidimensional Characterization and Differentiation of Neurons in the Anteroventral Cochlear Nucleus

PubMed Central

Typlt, Marei; Englitz, Bernhard; Sonntag, Mandy; Dehmel, Susanne; Kopp-Scheinpflug, Cornelia; Ruebsamen, Rudolf

2012-01-01

Multiple parallel auditory pathways ascend from the cochlear nucleus. It is generally accepted that the origin of these pathways are distinct groups of neurons differing in their anatomical and physiological properties. In extracellular in vivo recordings these neurons are typically classified on the basis of their peri-stimulus time histogram. In the present study we reconsider the question of classification of neurons in the anteroventral cochlear nucleus (AVCN) by taking a wider range of response properties into account. The study aims at a better understanding of the AVCN's functional organization and its significance as the source of different ascending auditory pathways. The analyses were based on 223 neurons recorded in the AVCN of the Mongolian gerbil. The range of analysed parameters encompassed spontaneous activity, frequency coding, sound level coding, as well as temporal coding. In order to categorize the unit sample without any presumptions as to the relevance of certain response parameters, hierarchical cluster analysis and additional principal component analysis were employed which both allow a classification on the basis of a multitude of parameters simultaneously. Even with the presently considered wider range of parameters, high number of neurons and more advanced analytical methods, no clear boundaries emerged which would separate the neurons based on their physiology. At the current resolution of the analysis, we therefore conclude that the AVCN units more likely constitute a multi-dimensional continuum with different physiological characteristics manifested at different poles. However, more complex stimuli could be useful to uncover physiological differences in future studies. PMID:22253838
Cochlear implant magnet retrofit.

PubMed

Cohen, N L; Breda, S D; Hoffman, R A

1988-06-01

An implantable magnet is now available for patients who have received the standard Nucleus 22-channel cochlear implant and who are not able to wear the headband satisfactorily. This magnet is attached in piggy-back fashion to the previously implanted receiver/stimulator by means of a brief operation under local anesthesia. Two patients have received this magnet retrofit, and are now wearing the headset with greater comfort and satisfaction. It is felt that the availability of this magnet will increase patient compliance in regard to hours of implant usage.

Evaluation of a wireless audio streaming accessory to improve mobile telephone performance of cochlear implant users.

PubMed

Wolfe, Jace; Morais Duke, Mila; Schafer, Erin; Cire, George; Menapace, Christine; O'Neill, Lori

2016-01-01

The objective of this study was to evaluate the potential improvement in word recognition in quiet and in noise obtained with use of a Bluetooth-compatible wireless hearing assistance technology (HAT) relative to the acoustic mobile telephone condition (e.g. the mobile telephone receiver held to the microphone of the sound processor). A two-way repeated measures design was used to evaluate differences in telephone word recognition obtained in quiet and in competing noise in the acoustic mobile telephone condition compared to performance obtained with use of the CI sound processor and a telephone HAT. Sixteen adult users of Nucleus cochlear implants and the Nucleus 6 sound processor were included in this study. Word recognition over the mobile telephone in quiet and in noise was significantly better with use of the wireless HAT compared to performance in the acoustic mobile telephone condition. Word recognition over the mobile telephone was better in quiet when compared to performance in noise. The results of this study indicate that use of a wireless HAT improves word recognition over the mobile telephone in quiet and in noise relative to performance in the acoustic mobile telephone condition for a group of adult cochlear implant recipients.
Dendrites of medial olivocochlear neurons in mouse.

PubMed

Brown, M C; Levine, J L

2008-06-12

Stains for acetylcholinesterase (AChE) and retrograde labeling with Fluorogold (FG) were used to study olivocochlear neurons and their dendritic patterns in mice. The two methods gave similar results for location and number of somata. The total number of medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body (VNTB) is about 170 per side. An additional dozen large olivocochlear neurons are located in the dorsal periolivary nucleus (DPO). Dendrites of all of these neurons are long and extend in all directions from the cell bodies, a pattern that contrasts with the sharp frequency tuning of their responses. For VNTB neurons, there were greater numbers of dendrites directed medially than laterally and those directed medially were longer (on average, 25-50% longer). Dendrite extensions were most pronounced for neurons located in the rostral portion of the VNTB. When each dendrite from a single neuron was represented as a vector, and all the vectors summed, the result was also skewed toward the medial direction. DPO neurons, however, had more symmetric dendrites that projected into more dorsal parts of the trapezoid body, suggesting that this small group of olivocochlear neurons has very different physiological properties. Dendrites of both types of neurons were somewhat elongated rostrally, about 20% longer than those directed caudally. These results can be interpreted as extensions of dendrites of olivocochlear neurons toward their synaptic inputs: medially to meet crossing fibers from the cochlear nucleus that are part of the MOC reflex pathway, and rostrally to meet descending inputs from higher centers.
A rapid method combining Golgi and Nissl staining to study neuronal morphology and cytoarchitecture.

PubMed

Pilati, Nadia; Barker, Matthew; Panteleimonitis, Sofoklis; Donga, Revers; Hamann, Martine

2008-06-01

The Golgi silver impregnation technique gives detailed information on neuronal morphology of the few neurons it labels, whereas the majority remain unstained. In contrast, the Nissl staining technique allows for consistent labeling of the whole neuronal population but gives very limited information on neuronal morphology. Most studies characterizing neuronal cell types in the context of their distribution within the tissue slice tend to use the Golgi silver impregnation technique for neuronal morphology followed by deimpregnation as a prerequisite for showing that neuron's histological location by subsequent Nissl staining. Here, we describe a rapid method combining Golgi silver impregnation with cresyl violet staining that provides a useful and simple approach to combining cellular morphology with cytoarchitecture without the need for deimpregnating the tissue. Our method allowed us to identify neurons of the facial nucleus and the supratrigeminal nucleus, as well as assessing cellular distribution within layers of the dorsal cochlear nucleus. With this method, we also have been able to directly compare morphological characteristics of neuronal somata at the dorsal cochlear nucleus when labeled with cresyl violet with those obtained with the Golgi method, and we found that cresyl violet-labeled cell bodies appear smaller at high cellular densities. Our observation suggests that cresyl violet staining is inadequate to quantify differences in soma sizes.
AutoNR: an automated system that measures ECAP thresholds with the Nucleus Freedom cochlear implant via machine intelligence.

PubMed

Botros, Andrew; van Dijk, Bas; Killian, Matthijs

2007-05-01

AutoNRT is an automated system that measures electrically evoked compound action potential (ECAP) thresholds from the auditory nerve with the Nucleus Freedom cochlear implant. ECAP thresholds along the electrode array are useful in objectively fitting cochlear implant systems for individual use. This paper provides the first detailed description of the AutoNRT algorithm and its expert systems, and reports the clinical success of AutoNRT to date. AutoNRT determines thresholds by visual detection, using two decision tree expert systems that automatically recognise ECAPs. The expert systems are guided by a dataset of 5393 neural response measurements. The algorithm approaches threshold from lower stimulus levels, ensuring recipient safety during postoperative measurements. Intraoperative measurements use the same algorithm but proceed faster by beginning at stimulus levels much closer to threshold. When searching for ECAPs, AutoNRT uses a highly specific expert system (specificity of 99% during training, 96% during testing; sensitivity of 91% during training, 89% during testing). Once ECAPs are established, AutoNRT uses an unbiased expert system to determine an accurate threshold. Throughout the execution of the algorithm, recording parameters (such as implant amplifier gain) are automatically optimised when needed. In a study that included 29 intraoperative and 29 postoperative subjects (a total of 418 electrodes), AutoNRT determined a threshold in 93% of cases where a human expert also determined a threshold. When compared to the median threshold of multiple human observers on 77 randomly selected electrodes, AutoNRT performed as accurately as the 'average' clinician. AutoNRT has demonstrated a high success rate and a level of performance that is comparable with human experts. It has been used in many clinics worldwide throughout the clinical trial and commercial launch of Nucleus Custom Sound Suite, significantly streamlining the clinical procedures associated with cochlear implant use.
The cochlear implant as a tinnitus treatment.

PubMed

Vallés-Varela, Héctor; Royo-López, Juan; Carmen-Sampériz, Luis; Sebastián-Cortés, José M; Alfonso-Collado, Ignacio

2013-01-01

Tinnitus is a symptom of high prevalence in patients with cochlear pathology. We studied the evolution of tinnitus in patients undergoing unilateral cochlear implantation for treatment of profound hearing loss. This was a longitudinal, retrospective study of patients that underwent unilateral cochlear implantation and who had bilateral tinnitus. Tinnitus was assessed quantitatively and qualitatively before surgery and at 6 and 12 months after surgery. We evaluated 20 patients that underwent unilateral cochlear implantation with a Nucleus(®) CI24RE Contour Advance™ electrode device. During the periods in which the device was in operation, improvement or disappearance of tinnitus was evidenced in the ipsilateral ear in 65% of patients, and in the contralateral ear, in 50%. In periods in which the device was disconnected, improvement or disappearance of tinnitus was found in the ipsilateral ear in 50% of patients, and in the ear contralateral to the implant in 45% of the patients. In 10% of the patients, a new tinnitus appeared in the ipsilateral ear. The patients with profound hearing loss and bilateral tinnitus treated with unilateral cochlear implantation improved in a high percentage of cases, in the ipsilateral ear and in the contralateral ear. Copyright © 2012 Elsevier España, S.L. All rights reserved.
The Pattern and Degree of Capsular Fibrous Sheaths Surrounding Cochlear Electrode Arrays

PubMed Central

Ishai, Reuven; Herrmann, Barbara S.; Nadol, Joseph B.; Quesnel, Alicia M.

2017-01-01

An inflammatory tissue reaction around the electrode array of a cochlear implant (CI) is common, in particular at the electrode insertion region (cochleostomy) where mechanical trauma often occurs. However, the factors determining the amount and causes of fibrous reaction surrounding the stimulating electrode, especially medially near the perimodiolar location, are unclear. Temporal bone (TB) specimens from patients who had undergone cochlear implantation during life with either Advanced Bionics (AB) Clarion TM or HiRes90KTM (Sylmar, CA, USA) or Cochlear TM Nucleus (Sydney, Australia) devices were evaluated. The thickness of the fibrous tissue surrounding the electrode array of both types of CI devices at both the lower (LB) and upper (UB) basal turns of the cochlea was quantified at three locations: the medial, inferior, and superior aspects of the sheath. Fracture of the osseous spiral lamina and/or marked displacement of the basilar membrane were interpreted as evidence of intracochlear trauma. In addition, post-operative word recognition scores, duration of implantation, and post-operative programming data were evaluated. Seven TBs from six patients implanted with AB devices and five TBs from five patients implanted with Nucleus devices were included. A fibrous capsule around the stimulating electrode array was present in all twelve specimens. TBs implanted with AB device had a significantly thicker fibrous capsule at the medial aspect than at the inferior or superior aspects at both locations (LB and UB) of the cochlea (Wilcoxon signed-ranks test, p<0.01). TBs implanted with a Nucleus device had no difference in the thickness of the fibrous capsule surrounding the track of the electrode array (Wilcoxon signed-ranks test, p>0.05). Nine of fourteen (64%) basal turns of the cochlea (LB and UB of seven TBs) implanted with AB devices demonstrated intracochlear trauma compared to two of ten (20%) basal turns of the cochlea (LB and UB of five TBs) with Nucleus devices, (Fisher exact test, p<0.05). There was no significant correlation between the thickness of the fibrous tissue and the duration of implantation or the word recognition scores (Spearman rho, p=0.06, p=0.4 respectively). Our outcomes demonstrated the development of a robust fibrous tissue sheath medially closest to the site of electric stimulation in cases implanted with the AB device electrode, but not in cases implanted with the Nucleus device. The cause of the asymmetric fibrous sheath may be multifactorial including insertional trauma, a foreign body response, and/or asymmetric current flow. PMID:28216124
Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing.

PubMed

Zong, Liang; Chen, Jin; Zhu, Yan; Zhao, Hong-Bo

2017-07-22

Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low frequency regions, first occurring in the high frequency region and then progressively extending to the middle and low frequency regions with mouse age increased. The speed of hearing loss extending was fast in the basal high frequency region and slow in the apical low frequency region, showing a logarithmic function with mouse age. Before postnatal day 25, there were no significant hearing loss and the reduction of active cochlear amplification in the low frequency region. Hearing loss and the reduction of active cochlear amplification also had frequency difference, severe and large in the high frequency regions. These new data indicate that the effect of gap junction on active cochlear amplification is progressive, but, consistent with our previous report, exists in both high and low frequency regions in adulthood. These new data also suggest that cochlear gap junctions may have an important role in age-related hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.
Development and validation of the University of Washington Clinical Assessment of Music Perception test.

PubMed

Kang, Robert; Nimmons, Grace Liu; Drennan, Ward; Longnion, Jeff; Ruffin, Chad; Nie, Kaibao; Won, Jong Ho; Worman, Tina; Yueh, Bevan; Rubinstein, Jay

2009-08-01

Assessment of cochlear implant outcomes centers around speech discrimination. Despite dramatic improvements in speech perception, music perception remains a challenge for most cochlear implant users. No standardized test exists to quantify music perception in a clinically practical manner. This study presents the University of Washington Clinical Assessment of Music Perception (CAMP) test as a reliable and valid music perception test for English-speaking, adult cochlear implant users. Forty-two cochlear implant subjects were recruited from the University of Washington Medical Center cochlear implant program and referred by two implant manufacturers. Ten normal-hearing volunteers were drawn from the University of Washington Medical Center and associated campuses. A computer-driven, self-administered test was developed to examine three specific aspects of music perception: pitch direction discrimination, melody recognition, and timbre recognition. The pitch subtest used an adaptive procedure to determine just-noticeable differences for complex tone pitch direction discrimination within the range of 1 to 12 semitones. The melody and timbre subtests assessed recognition of 12 commonly known melodies played with complex tones in an isochronous manner and eight musical instruments playing an identical five-note sequence, respectively. Testing was repeated for cochlear implant subjects to evaluate test-retest reliability. Normal-hearing volunteers were also tested to demonstrate differences in performance in the two populations. For cochlear implant subjects, pitch direction discrimination just-noticeable differences ranged from 1 to 8.0 semitones (Mean = 3.0, SD = 2.3). Melody and timbre recognition ranged from 0 to 94.4% correct (mean = 25.1, SD = 22.2) and 20.8 to 87.5% (mean = 45.3, SD = 16.2), respectively. Each subtest significantly correlated at least moderately with both Consonant-Nucleus-Consonant (CNC) word recognition scores and spondee recognition thresholds in steady state noise and two-talker babble. Intraclass coefficients demonstrating test-retest correlations for pitch, melody, and timbre were 0.85, 0.92, and 0.69, respectively. Normal-hearing volunteers had a mean pitch direction discrimination threshold of 1.0 semitone, the smallest interval tested, and mean melody and timbre recognition scores of 87.5 and 94.2%, respectively. The CAMP test discriminates a wide range of music perceptual ability in cochlear implant users. Moderate correlations were seen between music test results and both Consonant-Nucleus-Consonant word recognition scores and spondee recognition thresholds in background noise. Test-retest reliability was moderate to strong. The CAMP test provides a reliable and valid metric for a clinically practical, standardized evaluation of music perception in adult cochlear implant users.
Intracellular responses of onset chopper neurons in the ventral cochlear nucleus to tones: evidence for dual-component processing.

PubMed

Paolini, A G; Clark, G M

1999-05-01

Intracellular responses of onset chopper neurons in the ventral cochlear nucleus to tones: evidence for dual-component processing. The ventral cochlear nucleus (VCN) contains a heterogeneous collection of cell types reflecting the multiple processing tasks undertaken by this nucleus. This in vivo study in the rat used intracellular recordings and dye filling to examine membrane potential changes and firing characteristics of onset chopper (OC) neurons to acoustic stimulation (50 ms pure tones, 5 ms r/f time). Stable impalements were made from 15 OC neurons, 7 identified as multipolar cells. Neurons responded to characteristic frequency (CF) tones with sustained depolarization below spike threshold. With increasing stimulus intensity, the depolarization during the initial 10 ms of the response became peaked, and with further increases in intensity the peak became narrower. Onset spikes were generated during this initial depolarization. Tones presented below CF resulted in a broadening of this initial depolarizing component with high stimulus intensities required to initiate onset spikes. This initial component was followed by a sustained depolarizing component lasting until stimulus cessation. The amplitude of the sustained depolarizing component was greatest when frequencies were presented at high intensities below CF resulting in increased action potential firing during this period when compared with comparable high intensities at CF. During the presentation of tones at or above the high-frequency edge of a cell's response area, hyperpolarization was evident during the sustained component. The presence of hyperpolarization and the differences seen in the level of sustained depolarization during CF and off CF tones suggests that changes in membrane responsiveness between the initial and sustained components may be attributed to polysynaptic inhibitory mechanisms. The dual-component processing resulting from convergent auditory nerve excitation and polysynaptic inhibition enables OC neurons to respond in a unique fashion to intensity and frequency features contained within an acoustic stimulus.
Contralateral Effects and Binaural Interactions in Dorsal Cochlear Nucleus

PubMed Central

2005-01-01

The dorsal cochlear nucleus (DCN) receives afferent input from the auditory nerve and is thus usually thought of as a monaural nucleus, but it also receives inputs from the contralateral cochlear nucleus as well as descending projections from binaural nuclei. Evidence suggests that some of these commissural and efferent projections are excitatory, whereas others are inhibitory. The goals of this study were to investigate the nature and effects of these inputs in the DCN by measuring DCN principal cell (type IV unit) responses to a variety of contralateral monaural and binaural stimuli. As expected, the results of contralateral stimulation demonstrate a mixture of excitatory and inhibitory influences, although inhibitory effects predominate. Most type IV units are weakly, if at all, inhibited by tones but are strongly inhibited by broadband noise (BBN). The inhibition evoked by BBN is also low threshold and short latency. This inhibition is abolished and excitation is revealed when strychnine, a glycine-receptor antagonist, is applied to the DCN; application of bicuculline, a GABAA-receptor antagonist, has similar effects but does not block the onset of inhibition. Manipulations of discrete fiber bundles suggest that the inhibitory, but not excitatory, inputs to DCN principal cells enter the DCN via its output pathway, and that the short latency inhibition is carried by commissural axons. Consistent with their respective monaural effects, responses to binaural tones as a function of interaural level difference are essentially the same as responses to ipsilateral tones, whereas binaural BBN responses decrease with increasing contralateral level. In comparison to monaural responses, binaural responses to virtual space stimuli show enhanced sensitivity to the elevation of a sound source in ipsilateral space but reduced sensitivity in contralateral space. These results show that the contralateral inputs to the DCN are functionally relevant in natural listening conditions, and that one role of these inputs is to enhance DCN processing of spectral sound localization cues produced by the pinna. PMID:16075189
Speech understanding in background noise with the two-microphone adaptive beamformer BEAM in the Nucleus Freedom Cochlear Implant System.

PubMed

Spriet, Ann; Van Deun, Lieselot; Eftaxiadis, Kyriaky; Laneau, Johan; Moonen, Marc; van Dijk, Bas; van Wieringen, Astrid; Wouters, Jan

2007-02-01

This paper evaluates the benefit of the two-microphone adaptive beamformer BEAM in the Nucleus Freedom cochlear implant (CI) system for speech understanding in background noise by CI users. A double-blind evaluation of the two-microphone adaptive beamformer BEAM and a hardware directional microphone was carried out with five adult Nucleus CI users. The test procedure consisted of a pre- and post-test in the lab and a 2-wk trial period at home. In the pre- and post-test, the speech reception threshold (SRT) with sentences and the percentage correct phoneme scores for CVC words were measured in quiet and background noise at different signal-to-noise ratios. Performance was assessed for two different noise configurations (with a single noise source and with three noise sources) and two different noise materials (stationary speech-weighted noise and multitalker babble). During the 2-wk trial period at home, the CI users evaluated the noise reduction performance in different listening conditions by means of the SSQ questionnaire. In addition to the perceptual evaluation, the noise reduction performance of the beamformer was measured physically as a function of the direction of the noise source. Significant improvements of both the SRT in noise (average improvement of 5-16 dB) and the percentage correct phoneme scores (average improvement of 10-41%) were observed with BEAM compared to the standard hardware directional microphone. In addition, the SSQ questionnaire and subjective evaluation in controlled and real-life scenarios suggested a possible preference for the beamformer in noisy environments. The evaluation demonstrates that the adaptive noise reduction algorithm BEAM in the Nucleus Freedom CI-system may significantly increase the speech perception by cochlear implantees in noisy listening conditions. This is the first monolateral (adaptive) noise reduction strategy actually implemented in a mainstream commercial CI.
A Rapid Method Combining Golgi and Nissl Staining to Study Neuronal Morphology and Cytoarchitecture

PubMed Central

Pilati, Nadia; Barker, Matthew; Panteleimonitis, Sofoklis; Donga, Revers; Hamann, Martine

2008-01-01

The Golgi silver impregnation technique gives detailed information on neuronal morphology of the few neurons it labels, whereas the majority remain unstained. In contrast, the Nissl staining technique allows for consistent labeling of the whole neuronal population but gives very limited information on neuronal morphology. Most studies characterizing neuronal cell types in the context of their distribution within the tissue slice tend to use the Golgi silver impregnation technique for neuronal morphology followed by deimpregnation as a prerequisite for showing that neuron's histological location by subsequent Nissl staining. Here, we describe a rapid method combining Golgi silver impregnation with cresyl violet staining that provides a useful and simple approach to combining cellular morphology with cytoarchitecture without the need for deimpregnating the tissue. Our method allowed us to identify neurons of the facial nucleus and the supratrigeminal nucleus, as well as assessing cellular distribution within layers of the dorsal cochlear nucleus. With this method, we also have been able to directly compare morphological characteristics of neuronal somata at the dorsal cochlear nucleus when labeled with cresyl violet with those obtained with the Golgi method, and we found that cresyl violet–labeled cell bodies appear smaller at high cellular densities. Our observation suggests that cresyl violet staining is inadequate to quantify differences in soma sizes. (J Histochem Cytochem 56:539–550, 2008) PMID:18285350
Atoh1-lineal neurons are required for hearing and for the survival of neurons in the spiral ganglion and brainstem accessory auditory nuclei

PubMed Central

Maricich, Stephen M.; Xia, Anping; Mathes, Erin L.; Wang, Vincent Y.; Oghalai, John S.; Fritzsch, Bernd; Zoghbi, Huda Y.

2009-01-01

Atoh1 is a basic helix-loop-helix transcription factor necessary for the specification of inner ear hair cells and central auditory system neurons derived from the rhombic lip. We used the Cre-loxP system and two Cre-driver lines (Egr2Cre and Hoxb1Cre) to delete Atoh1 from different regions of the cochlear nucleus (CN) and accessory auditory nuclei (AAN). Adult Atoh1-conditional knockout mice (Atoh1CKO) are behaviorally deaf, have diminished auditory brainstem evoked responses and disrupted CN and AAN morphology and connectivity. In addition, Egr2; Atoh1CKO mice lose spiral ganglion neurons in the cochlea and AAN neurons during the first 3 days of life, revealing a novel critical period in the development of these neurons. These new mouse models of predominantly central deafness illuminate the importance of the CN for support of a subset of peripheral and central auditory neurons. PMID:19741118
Developmental and cell-specific expression of thyroid hormone transporters in the mouse cochlea.

PubMed

Sharlin, David S; Visser, Theo J; Forrest, Douglas

2011-12-01

Thyroid hormone is essential for the development of the cochlea and auditory function. Cochlear response tissues, which express thyroid hormone receptor β (encoded by Thrb), include the greater epithelial ridge and sensory epithelium residing inside the bony labyrinth. However, these response tissues lack direct blood flow, implying that mechanisms exist to shuttle hormone from the circulation to target tissues. Therefore, we investigated expression of candidate thyroid hormone transporters L-type amino acid transporter 1 (Lat1), monocarboxylate transporter (Mct)8, Mct10, and organic anion transporting polypeptide 1c1 (Oatp1c1) in mouse cochlear development by in situ hybridization and immunofluorescence analysis. L-type amino acid transporter 1 localized to cochlear blood vessels and transiently to sensory hair cells. Mct8 localized to the greater epithelial ridge, tympanic border cells underlying the sensory epithelium, spiral ligament fibrocytes, and spiral ganglion neurons, partly overlapping with the Thrb expression pattern. Mct10 was detected in a highly restricted pattern in the outer sulcus epithelium and weakly in tympanic border cells and hair cells. Organic anion transporting polypeptide 1c1 localized primarily to fibrocytes in vascularized tissues of the spiral limbus and spiral ligament and to tympanic border cells. Investigation of hypothyroid Tshr(-/-) mice showed that transporter expression was delayed consistent with retardation of cochlear tissue maturation but not with compensatory responses to hypothyroidism. The results demonstrate specific expression of thyroid hormone transporters in the cochlea and suggest that a network of thyroid hormone transport underlies cochlear development.
[Correlation between the thresholds acquired with ASSR and sbjective thresholds in cochlear implants in prelingually deaf children].

PubMed

Wang, Z; Gu, J; Jiang, X J

2017-04-20

Objective: To learn the relationship between the auditory steady state responses(ASSR)threshold and C-level and behavior T-level in cochlear implants in prelingually deaf children. Method: One hundred and twelve children with Nucleus CI24R(CA) cochlear implants were divided into residual hearing group and no residual hearing group on the basis of the results of ASSR before operation in this study.Compare the difference between the two groups in C-level and behavior T-level one year after operation. Result: There was difference in C-level and behavior T-level between residual hearing group and no residual hearing group( P <0.05 or P <0.01). Conclusion: According to the results of ASSR before operation,we can estimate the effect of cochlear implants,providing reference for the selection of choosing operating ears,and providing a reasonable expectation for physicians and parents of the patients. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
Ten-year follow-up of a consecutive series of children with multichannel cochlear implants.

PubMed

Uziel, Alain S; Sillon, Martine; Vieu, Adrienne; Artieres, Françoise; Piron, Jean-Pierre; Daures, Jean-Pierre; Mondain, Michel

2007-08-01

To assess a group of children who consecutively received implants more than 10 years after implantation with regard to speech perception, speech intelligibility, receptive language level, and academic/occupational status. A prospective longitudinal study. Pediatric referral center for cochlear implantation. Eighty-two prelingually deafened children received the Nucleus multichannel cochlear implant. Cochlear implantation with Cochlear Nucleus CI22 implant. The main outcome measures were open-set Phonetically Balanced Kindergarten word test, discrimination of sentences in noise, connective discourse tracking (CDT) using voice and telephone, speech intelligibility rating (SIR), vocabulary knowledge measured using the Peabody Picture Vocabulary Test (Revised), academic performance on French language, foreign language, and mathematics, and academic/occupational status. After 10 years of implant experience, 79 children (96%) reported that they always wear the device; 79% (65 of 82 children) could use the telephone. The mean scores were 72% for the Phonetically Balanced Kindergarten word test, 44% for word recognition in noise, 55.3 words per minute for the CDT, and 33 words per minute for the CDT via telephone. Thirty-three children (40%) developed speech intelligible to the average listener (SIR 5), and 22 (27%) developed speech intelligible to a listener with little experience of deaf person's speech (SIR 4). The measures of vocabulary showed that most (76%) of children who received implants scored below the median value of their normally hearing peers. The age at implantation was the most important factor that may influence the postimplant outcomes. Regarding educational/vocational status, 6 subjects attend universities, 3 already have a professional activity, 14 are currently at high school level, 32 are at junior high school level, 6 additional children are enrolled in a special unit for children with disability, and 3 children are still attending elementary schools. Seventeen are in further noncompulsory education studying a range of subjects at vocational level. This long-term report shows that many profoundly hearing-impaired children using cochlear implants can develop functional levels of speech perception and production, attain age-appropriate oral language, develop competency level in a language other than their primary language, and achieve satisfactory academic performance.
The Mechanosensory Structure of the Hair Cell Requires Clarin-1, a Protein Encoded by Usher Syndrome III Causative Gene

PubMed Central

Geng, Ruishuang; Melki, Sami; Chen, Daniel H.-C.; Tian, Guilian; Furness, David; Oshima-Takago, Tomoko; Neef, Jakob; Moser, Tobias; Askew, Charles; Horwitz, Geoff; Holt, Jeffrey; Imanishi, Yoshikazu; Alagramam, Kumar N.

2012-01-01

Mutation in the clarin-1 gene results in loss of hearing and vision in humans (Usher syndrome III), but the role of clarin-1 in the sensory hair cells is unknown. Clarin-1 is predicted to be a four transmembrane domain protein similar to members of the tetraspanin family. Mice carrying null mutation in the clarin-1 (Clrn1−/−) gene show loss of hair cell function and a possible defect in ribbon synapse. We investigated the role of clarin-1 using various in vitro and in vivo approaches. We show by immunohistochemistry and patch-clamp recordings of Ca2+ currents and membrane capacitance from IHCs that clarin-1 is not essential for formation or function of ribbon synapse. However, reduced cochlear microphonic potentials, FM1-43 loading and transduction currents pointed to diminished cochlear hair bundle function in Clrn1−/− mice. Electron microscopy of cochlear hair cells revealed loss of some tall stereocilia and gaps in the v-shaped bundle, although tip-links and staircase arrangement of stereocilia were not primarily affected by Clrn1−/− mutation. Human clarin-1 protein expressed in transfected mouse cochlear hair cells localized to the bundle; however, the pathogenic variant, p.N48K, failed to localize to the bundle. The mouse model generated to study the in vivo consequence of p. N48K in clarin-1 (Clrn1N48K) supports our in vitro and Clrn1−/− mouse data and the conclusion that CLRN1 is an essential hair bundle protein. Further, the ear phenotype in the Clrn1N48K mouse suggests that it is a valuable model for ear disease in CLRN1N48K, the most prevalent Usher III mutation in North America. PMID:22787034
The mechanosensory structure of the hair cell requires clarin-1, a protein encoded by Usher syndrome III causative gene.

PubMed

Geng, Ruishuang; Melki, Sami; Chen, Daniel H-C; Tian, Guilian; Furness, David N; Oshima-Takago, Tomoko; Neef, Jakob; Moser, Tobias; Askew, Charles; Horwitz, Geoff; Holt, Jeffrey R; Imanishi, Yoshikazu; Alagramam, Kumar N

2012-07-11

Mutation in the clarin-1 gene (Clrn1) results in loss of hearing and vision in humans (Usher syndrome III), but the role of clarin-1 in the sensory hair cells is unknown. Clarin-1 is predicted to be a four transmembrane domain protein similar to members of the tetraspanin family. Mice carrying null mutation in the clarin-1 gene (Clrn1(-/-)) show loss of hair cell function and a possible defect in ribbon synapse. We investigated the role of clarin-1 using various in vitro and in vivo approaches. We show by immunohistochemistry and patch-clamp recordings of Ca(2+) currents and membrane capacitance from inner hair cells that clarin-1 is not essential for formation or function of ribbon synapse. However, reduced cochlear microphonic potentials, FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] loading, and transduction currents pointed to diminished cochlear hair bundle function in Clrn1(-/-) mice. Electron microscopy of cochlear hair cells revealed loss of some tall stereocilia and gaps in the v-shaped bundle, although tip links and staircase arrangement of stereocilia were not primarily affected by Clrn1(-/-) mutation. Human clarin-1 protein expressed in transfected mouse cochlear hair cells localized to the bundle; however, the pathogenic variant p.N48K failed to localize to the bundle. The mouse model generated to study the in vivo consequence of p.N48K in clarin-1 (Clrn1(N48K)) supports our in vitro and Clrn1(-/-) mouse data and the conclusion that CLRN1 is an essential hair bundle protein. Furthermore, the ear phenotype in the Clrn1(N48K) mouse suggests that it is a valuable model for ear disease in CLRN1(N48K), the most prevalent Usher syndrome III mutation in North America.
Quantitative polarized light microscopy of unstained mammalian cochlear sections

NASA Astrophysics Data System (ADS)

Kalwani, Neil M.; Ong, Cheng Ai; Lysaght, Andrew C.; Haward, Simon J.; McKinley, Gareth H.; Stankovic, Konstantina M.

2013-02-01

Hearing loss is the most common sensory deficit in the world, and most frequently it originates in the inner ear. Yet, the inner ear has been difficult to access for diagnosis because of its small size, delicate nature, complex three-dimensional anatomy, and encasement in the densest bone in the body. Evolving optical methods are promising to afford cellular diagnosis of pathologic changes in the inner ear. To appropriately interpret results from these emerging technologies, it is important to characterize optical properties of cochlear tissues. Here, we focus on that characterization using quantitative polarized light microscopy (qPLM) applied to unstained cochlear sections of the mouse, a common animal model of human hearing loss. We find that the most birefringent cochlear materials are collagen fibrils and myelin. Retardance of the otic capsule, the spiral ligament, and the basilar membrane are substantially higher than that of other cochlear structures. Retardance of the spiral ligament and the basilar membrane decrease from the cochlear base to the apex, compared with the more uniform retardance of other structures. The intricate structural details revealed by qPLM of unstained cochlear sections ex vivo strongly motivate future application of polarization-sensitive optical coherence tomography to human cochlea in vivo.
Quantitative polarized light microscopy of unstained mammalian cochlear sections

PubMed Central

Kalwani, Neil M.; Ong, Cheng Ai; Lysaght, Andrew C.; Haward, Simon J.; McKinley, Gareth H.

2013-01-01

Abstract. Hearing loss is the most common sensory deficit in the world, and most frequently it originates in the inner ear. Yet, the inner ear has been difficult to access for diagnosis because of its small size, delicate nature, complex three-dimensional anatomy, and encasement in the densest bone in the body. Evolving optical methods are promising to afford cellular diagnosis of pathologic changes in the inner ear. To appropriately interpret results from these emerging technologies, it is important to characterize optical properties of cochlear tissues. Here, we focus on that characterization using quantitative polarized light microscopy (qPLM) applied to unstained cochlear sections of the mouse, a common animal model of human hearing loss. We find that the most birefringent cochlear materials are collagen fibrils and myelin. Retardance of the otic capsule, the spiral ligament, and the basilar membrane are substantially higher than that of other cochlear structures. Retardance of the spiral ligament and the basilar membrane decrease from the cochlear base to the apex, compared with the more uniform retardance of other structures. The intricate structural details revealed by qPLM of unstained cochlear sections ex vivo strongly motivate future application of polarization-sensitive optical coherence tomography to human cochlea in vivo. PMID:23407909

[The Impact of Electroacupuncture Intervention on Expression of 5-HTR 1 B/2 C Genes in Mice under Radiation Stimulation from Mobile Phone].

PubMed

Dai, Jian-yu; Chen, Yi-guo; Zhang, Xiao-qing

2015-08-01

To observe the effect of electroacupuncture (EA) stimulation of "Yifen" (TE 17), "Shenshu" (BL 23) on the expression of 5-hydroxytryptamine receptor 1 B (5-HTR 1 B) mRNA and 5-hydroxytryptamine receptor 2 C (5-HTR 2 C) mRNA in the cochlear nucleus tissue in mice experiencing radiation from mobile phone, so as to explore its mechanisms underlying improvement of tinnitus. Thirty Kunming mice were randomly divided into control group (n = 6) and modeling group (n = 24). The tinnitus model was established by giving the mice with mobile phone-radiation for 1 h in the morning and 1 h in the afternoon, continuously for 40 days. EA stimulation was applied to "Yifeng" (TE 17) group (n = 6) and "Shenshu" (BL 23) group (n = 6) for 20 min, once a day for 7 days. The expression of 5-THR 1 B/2 C mRNA in the cochlear nucleus was assayed by fluorescence quantitative polymerase chain reaction (real time-PCR). The expression level of 5-HTR 1 B was significantly lower in the model group than in the control group (P < 0.05), while that of 5-HTR 2 C mRNA significantly increased (P < 0.01). TE 17 group received a significant acupoint intervention effect (P < 0.01). Compared with TE 17 group, BL 23 group received a weaker effect (P < 0.05). EA of TE 17 can up-regulate expression level of 5-HTR 1 B and down-regulate expression level of 5-HTR 2 C in the cochlear nucleus in mice experiencing mobile-phone radiation.
Physiological correlates of comodulation masking release in the mammalian ventral cochlear nucleus.

PubMed

Pressnitzer, D; Meddis, R; Delahaye, R; Winter, I M

2001-08-15

Comodulation masking release (CMR) enhances the detection of signals embedded in wideband, amplitude-modulated maskers. At least part of the CMR is attributable to across-frequency processing, however, the relative contribution of different stages in the auditory system to across-frequency processing is unknown. We have measured the responses of single units from one of the earliest stages in the ascending auditory pathway, the ventral cochlear nucleus, where across frequency processing may take place. A sinusoidally amplitude-modulated tone at the best frequency of each unit was used as a masker. A pure tone signal was added in the dips of the masker modulation (reference condition). Flanking components (FCs) were then added at frequencies remote from the unit best frequency. The FCs were pure tones amplitude modulated either in phase (comodulated) or out of phase (codeviant) with the on-frequency component. Psychophysically, this CMR paradigm reduces within-channel cues while producing an advantage of approximately 10 dB for the comodulated condition in comparison with the reference condition. Some of the recorded units showed responses consistent with perceptual CMR. The addition of the comodulated FCs produced a strong reduction in the response to the masker modulation, making the signal more salient in the poststimulus time histograms. A decision statistic based on d' showed that threshold was reached at lower signal levels for the comodulated condition than for reference or codeviant conditions. The neurons that exhibited such a behavior were mainly transient chopper or primary-like units. The results obtained from a subpopulation of transient chopper units are consistent with a possible circuit in the cochlear nucleus consisting of a wideband inhibitor contacting a narrowband cell. A computational model was used to confirm the feasibility of such a circuit.
Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus.

PubMed

Sedlacek, Miloslav; Brenowitz, Stephan D

2014-01-01

Feed-forward inhibition (FFI) represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs), principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and FFI in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition, we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.
The pattern and degree of capsular fibrous sheaths surrounding cochlear electrode arrays.

PubMed

Ishai, Reuven; Herrmann, Barbara S; Nadol, Joseph B; Quesnel, Alicia M

2017-05-01

An inflammatory tissue reaction around the electrode array of a cochlear implant (CI) is common, in particular at the electrode insertion region (cochleostomy) where mechanical trauma often occurs. However, the factors determining the amount and causes of fibrous reaction surrounding the stimulating electrode, especially medially near the perimodiolar location, are unclear. Temporal bone (TB) specimens from patients who had undergone cochlear implantation during life with either Advanced Bionics (AB) Clarion ™ or HiRes90K™ (Sylmar, CA, USA) devices that have a half-band and a pre-curved electrode, or Cochlear ™ Nucleus (Sydney, Australia) device that have a full-band and a straight electrode were evaluated. The thickness of the fibrous tissue surrounding the electrode array of both types of CI devices at both the lower (LB) and upper (UB) basal turns of the cochlea was quantified at three locations: the medial, inferior, and superior aspects of the sheath. Fracture of the osseous spiral lamina and/or marked displacement of the basilar membrane were interpreted as evidence of intracochlear trauma. In addition, post-operative word recognition scores, duration of implantation, and post-operative programming data were evaluated. Seven TBs from six patients implanted with AB devices and five TBs from five patients implanted with Nucleus devices were included. A fibrous capsule around the stimulating electrode array was present in all twelve specimens. TBs implanted with AB device had a significantly thicker fibrous capsule at the medial aspect than at the inferior or superior aspects at both locations (LB and UB) of the cochlea (Wilcoxon signed-ranks test, p < 0.01). TBs implanted with a Nucleus device had no difference in the thickness of the fibrous capsule surrounding the track of the electrode array (Wilcoxon signed-ranks test, p > 0.05). Nine of fourteen (64%) basal turns of the cochlea (LB and UB of seven TBs) implanted with AB devices demonstrated intracochlear trauma compared to two of ten (20%) basal turns of the cochlea (LB and UB of five TBs) with Nucleus devices, (Fisher exact test, p < 0.05). There was no significant correlation between the thickness of the fibrous tissue and the duration of implantation or the word recognition scores (Spearman rho, p = 0.06, p = 0.4 respectively). Our outcomes demonstrated the development of a robust fibrous tissue sheath medially closest to the site of electric stimulation in cases implanted with the AB device electrode, but not in cases implanted with the Nucleus device. The cause of the asymmetric fibrous sheath may be multifactorial including insertional trauma, a foreign body response, and/or asymmetric current flow. Copyright © 2017 Elsevier B.V. All rights reserved.
Evidence-based guidelines for recommending cochlear implantation for postlingually deafened adults.

PubMed

Leigh, Jaime R; Moran, Michelle; Hollow, Rodney; Dowell, Richard C

2016-01-01

Adult selection criteria for cochlear implantation have been developed based on analysis of the post-operative performance of a large group of postlingually deafened adults. Original criteria published in 2004 were reviewed and amended to reflect outcomes currently being achieved by implant recipients. Retrospective review of 12-month post-operative speech perception performance of adults implanted at the Eye and Ear Hospital, Melbourne, Australia. A total of 382 postlingually deafened adults, using a Freedom, Nucleus 5, or CI422 Slim Straight cochlear implant were used to create a comparative set of data. Revised guidelines suggest that adults with postlingual hearing loss can now be considered cochlear implant candidates if they obtain scores of up to 55% for open-set phonemes in quiet in the ear to be implanted. Functional benefit may vary depending on the recipients' contralateral hearing. This study supports the provision of cochlear implants to candidates with significant residual hearing when at least one ear meets the criterion outlined above. Patient-specific counseling is required to ensure the potential to benefit predicted by the current model is acceptable to the individual patient and their family. Counseling regarding functional benefit must take into consideration hearing in the contralateral ear.
Quality-of-life benefit from cochlear implantation in the elderly.

PubMed

Vermeire, Katrien; Brokx, Jan P L; Wuyts, Floris L; Cochet, Ellen; Hofkens, Anouk; Van de Heyning, Paul H

2005-03-01

To compare the audiologic results of geriatric patients receiving cochlear implants with younger age groups and to evaluate the quality of life after cochlear implantation in the geriatric population by means of validated quality-of-life questionnaires. Cross-sectional study involving 89 postlingually deafened cochlear implant subjects. Tertiary referral center. A total of 89 postlingually deafened patients were included in the study, among which were 25 patients who were aged 70 years or older. All patients received a cochlear implant. Subjects were implanted with either the Laura, Nucleus 24, or Med-el Combi 40+ cochlear implant systems implementing the SPEAK, ACE, CIS, or CIS+ coding strategies. Speech recognition was determined by means of phonetically balanced monosyllabic word lists. The Hearing Handicap Inventory for Adults, the Glasgow Benefit Inventory, and the scale for the prediction of hearing disability in sensorineural hearing loss were used to quantify the quality of life. Mean audiologic performance for the three groups increased significantly after implantation (p < 0.001). Postoperative audiologic performance of the geriatric population led to useful hearing, but these scores were significantly lower than for the younger age groups (p = 0.002). However, the quality-of-life outcomes for the geriatric group were similar to those of the younger age groups (p = 0.411 for the Hearing Handicap Inventory for Adults; p = 0.886 for the Glasgow Benefit Inventory). The results of this study prove that cochlear implantation in the elderly provides improvements in quality of life and speech understanding, similar to those for younger adult cochlear implant recipients.
Clinical investigation of the Nucleus Slim Modiolar Electrode.

PubMed

Aschendorff, Antje; Briggs, Robert; Brademann, Goetz; Helbig, Silke; Hornung, Joachim; Lenarz, Thomas; Marx, Mathieu; Ramos, Angel; Stöver, Timo; Escudé, Bernard; James, Chris J

2017-01-01

The Nucleus CI532 cochlear implant incorporates a new precurved electrode array, i.e., the Slim Modiolar electrode (SME), which is designed to bring electrode contacts close to the medial wall of the cochlea while avoiding trauma due to scalar dislocation or contact with the lateral wall during insertion. The primary aim of this prospective study was to determine the final position of the electrode array in clinical cases as evaluated using flat-panel volume computed tomography. Forty-five adult candidates for unilateral cochlear implantation were recruited from 8 centers. Eleven surgeons attended a temporal bone workshop and received further training with a transparent plastic cochlear model just prior to the first surgery. Feedback on the surgical approach and use of the SME was collected via a questionnaire for each case. Computed tomography of the temporal bone was performed postoperatively using flat-panel digital volume tomography or cone beam systems. The primary measure was the final scalar position of the SME (completely in scala tympani or not). Secondly, medial-lateral position and insertion depth were evaluated. Forty-four subjects received a CI532. The SME was located completely in scala tympani for all subjects. Pure round window (44% of the cases), extended round window (22%), and inferior and/or anterior cochleostomy (34%) approaches were successful across surgeons and cases. The SME was generally positioned close to the modiolus. Overinsertion of the array past the first marker tended to push the basal contacts towards the lateral wall and served only to increase the insertion depth of the first electrode contact without increasing the insertion depth of the most apical electrode. Complications were limited to tip fold-overs encountered in 2 subjects; both were attributed to surgical error, with both reimplanted successfully. The new Nucleus CI532 cochlear implant with SME achieved the design goal of producing little or no trauma as indicated by consistent scala tympani placement. Surgeons should be carefully trained to use the new deployment method such that tip fold-overs and over insertion may be avoided. © 2017 S. Karger AG, Basel.
Encoding of the amplitude modulation of pulsatile electrical stimulation in the feline cochlear nucleus by neurons in the inferior colliculus; effects of stimulus pulse rate

NASA Astrophysics Data System (ADS)

McCreery, Douglas; Han, Martin; Pikov, Victor; Yadav, Kamal; Pannu, Satinderpall

2013-10-01

Objectives. Persons without a functional auditory nerve cannot benefit from cochlear implants, but some hearing can be restored by an auditory brainstem implant (ABI) with stimulating electrodes implanted on the surface of the cochlear nucleus (CN). Most users benefit from their ABI, but speech recognition tends to be poorer than for users of cochlear implants. Psychophysical studies suggest that poor modulation detection may contribute to the limited performance of ABI users. In a cat model, we determined how the pulse rate of the electrical stimulus applied within or on the CN affects temporal and rate encoding of amplitude modulation (AM) by neurons in the central nucleus of the inferior colliculus (ICC). Approach. Stimulating microelectrodes were implanted chronically in and on the cats' CN, and multi-site recording microelectrodes were implanted chronically into the ICC. Encoding of AM pulse trains by neurons in the ICC was characterized as vector strength (VS), the synchrony of neural activity with the AM, and as the mean rate of neuronal action potentials (neuronal spike rate (NSR)). Main results. For intranuclear microstimulation, encoding of AM as VS was up to 3 dB greater when stimulus pulse rate was increased from 250 to 500 pps, but only for neuronal units with low best acoustic frequencies, and when the electrical stimulation was modulated at low frequencies (10-20 Hz). For stimulation on the surface of the CN, VS was similar at 250 and 500 pps, and the dynamic range of the VS was reduced for pulse rates greater than 250 pps. Modulation depth was encoded strongly as VS when the maximum stimulus amplitude was held constant across a range of modulation depth. This ‘constant maximum’ protocol allows enhancement of modulation depth while preserving overall dynamic range. However, modulation depth was not encoded as strongly as NSR. Significance. The findings have implications for improved sound processors for present and future ABIs. The performance of ABIs may benefit from using pulse rates greater than those presently used in most ABIs, and by sound processing strategies that enhance the modulation depth of the electrical stimulus while preserving dynamic range.
Modeling Sound Processing in Cochlear Nuclei

NASA Astrophysics Data System (ADS)

Meddis, Ray

2003-03-01

The cochlear nucleus is an obligatory relay nucleus between the ear and the rest of the brain. It consists of many different types of neurons each responding differently to the same stimulus. Much is known about the wiring diagram of the system but it has so far proved difficult to characterise the signal processing that is going on or what purpose it serves. The solution to this problem is a pre-requisite of any attempt to produce a practical electronic simulation that exploits the brain's unique capacity to recognise the significance of acoustic events and generate appropriate responses. This talk will explain the different types of neural cell and specify hypotheses as to their various functions. Cell-types vary in terms of their size and shape as well as the number and type of minute electrical currents that flow across the cell membranes. Computer models will also be used to illustrate how the physical substrate (the wet-ware) is used to achieve its signal-processing goals.
Effect of increased IIDR in the nucleus freedom cochlear implant system.

PubMed

Holden, Laura K; Skinner, Margaret W; Fourakis, Marios S; Holden, Timothy A

2007-10-01

The objective of this study was to evaluate the effect of the increased instantaneous input dynamic range (IIDR) in the Nucleus Freedom cochlear implant (CI) system on recipients' ability to perceive soft speech and speech in noise. Ten adult Freedom CI recipients participated. Two maps differing in IIDR were placed on each subject's processor at initial activation. The IIDR was set to 30 dB for one map and 40 dB for the other. Subjects used both maps for at least one month prior to speech perception testing. Results revealed significantly higher scores for words (50 dB SPL), for sentences in background babble (65 dB SPL), and significantly lower sound field threshold levels with the 40 compared to the 30 dB IIDR map. Ceiling effects may have contributed to non-significant findings for sentences in quiet (50 dB SPL). The Freedom's increased IIDR allows better perception of soft speech and speech in noise.
Developmental and Cell-Specific Expression of Thyroid Hormone Transporters in the Mouse Cochlea

PubMed Central

Sharlin, David S.; Visser, Theo J.

2011-01-01

Thyroid hormone is essential for the development of the cochlea and auditory function. Cochlear response tissues, which express thyroid hormone receptor β (encoded by Thrb), include the greater epithelial ridge and sensory epithelium residing inside the bony labyrinth. However, these response tissues lack direct blood flow, implying that mechanisms exist to shuttle hormone from the circulation to target tissues. Therefore, we investigated expression of candidate thyroid hormone transporters L-type amino acid transporter 1 (Lat1), monocarboxylate transporter (Mct)8, Mct10, and organic anion transporting polypeptide 1c1 (Oatp1c1) in mouse cochlear development by in situ hybridization and immunofluorescence analysis. L-type amino acid transporter 1 localized to cochlear blood vessels and transiently to sensory hair cells. Mct8 localized to the greater epithelial ridge, tympanic border cells underlying the sensory epithelium, spiral ligament fibrocytes, and spiral ganglion neurons, partly overlapping with the Thrb expression pattern. Mct10 was detected in a highly restricted pattern in the outer sulcus epithelium and weakly in tympanic border cells and hair cells. Organic anion transporting polypeptide 1c1 localized primarily to fibrocytes in vascularized tissues of the spiral limbus and spiral ligament and to tympanic border cells. Investigation of hypothyroid Tshr−/− mice showed that transporter expression was delayed consistent with retardation of cochlear tissue maturation but not with compensatory responses to hypothyroidism. The results demonstrate specific expression of thyroid hormone transporters in the cochlea and suggest that a network of thyroid hormone transport underlies cochlear development. PMID:21878515
[Site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials and refractory using the Nucleus 24 standard].

PubMed

Ma, R Y; Li, W; Jiang, X J

2016-12-01

Objective: To investigate the correlation between the site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials. Method: Recordings of auditory nerve responses were conducted in 32 prelingual subjects to demonstrate the feasibility of ECAP recordings using the nerve response telemetry(NRT) feature of the Nucleus CI24R(CA) system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Result: Findings of our prelingual children showed significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function hadbeen observed. The refractory time showed an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusion: Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences between prelingual children and adults could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
Origin and function of short-latency inputs to the neural substrates underlying the acoustic startle reflex

PubMed Central

Gómez-Nieto, Ricardo; Horta-Júnior, José de Anchieta C.; Castellano, Orlando; Millian-Morell, Lymarie; Rubio, Maria E.; López, Dolores E.

2014-01-01

The acoustic startle reflex (ASR) is a survival mechanism of alarm, which rapidly alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR circuit encompasses three serially connected structures: cochlear root neurons (CRNs), neurons in the caudal pontine reticular nucleus (PnC), and motoneurons in the medulla and spinal cord. It is well-established that both CRNs and PnC neurons receive short-latency auditory inputs to mediate the ASR. Here, we investigated the anatomical origin and functional role of these inputs using a multidisciplinary approach that combines morphological, electrophysiological and behavioral techniques. Anterograde tracer injections into the cochlea suggest that CRNs somata and dendrites receive inputs depending, respectively, on their basal or apical cochlear origin. Confocal colocalization experiments demonstrated that these cochlear inputs are immunopositive for the vesicular glutamate transporter 1 (VGLUT1). Using extracellular recordings in vivo followed by subsequent tracer injections, we investigated the response of PnC neurons after contra-, ipsi-, and bilateral acoustic stimulation and identified the source of their auditory afferents. Our results showed that the binaural firing rate of PnC neurons was higher than the monaural, exhibiting higher spike discharges with contralateral than ipsilateral acoustic stimulations. Our histological analysis confirmed the CRNs as the principal source of short-latency acoustic inputs, and indicated that other areas of the cochlear nucleus complex are not likely to innervate PnC. Behaviorally, we observed a strong reduction of ASR amplitude in monaural earplugged rats that corresponds with the binaural summation process shown in our electrophysiological findings. Our study contributes to understand better the role of neuronal mechanisms in auditory alerting behaviors and provides strong evidence that the CRNs-PnC pathway mediates fast neurotransmission and binaural summation of the ASR. PMID:25120419
Somatosensory Projections to Cochlear Nucleus are Up-regulated after Unilateral Deafness

PubMed Central

Zeng, Chunhua; Yang, Ziheng; Shreve, Lauren; Bledsoe, Sanford; Shore, Susan

2012-01-01

The cochlear nucleus (CN) receives innervation from auditory and somatosensory structures, which can be identified using vesicular glutamate transporters, VGLUT1 and VGLUT2. VGLUT1 is highly expressed in the magnocellular ventral CN (VCN), which receives auditory nerve inputs. VGLUT2 is predominantly expressed in the granule cell domain (GCD), which receives non-auditory inputs from somatosensory nuclei, including spinal trigeminal nucleus (Sp5) and cuneate nucleus (Cu). Two weeks after unilateral deafening VGLUT1 is significantly decreased in ipsilateral VCN while VGLUT2 is significantly increased in the ipsilateral GCD (Zeng et al., 2009), putatively reflecting decreased inputs from auditory nerve and increased inputs from non-auditory structures in guinea pigs. Here we wished to determine whether the upregulation of VGLUT2 represents increases in the number of somatosensory projections to the CN that are maintained for longer periods of time. Thus we examined concurrent changes in VGLUT levels and somatosensory projections in the CN using immunohistochemistry combined with anterograde tract tracing three and six weeks following unilateral deafening. The data reveal that unilateral deafness leads to increased numbers of VGLUT2-colabeled Sp5 and Cu projections to the ventral and dorsal CN. These findings suggest that Sp5 and Cu play significant and unique roles in cross-modal compensation and that, unlike after shorter term deafness, neurons in the magnocelluar regions also participate in the compensation. The enhanced glutamatergic somatosensory projections to the CN may play a role in neural spontaneous hyperactivity associated with tinnitus. PMID:23136418
Preparation for the Implantation of an Intracortical Visual Prosthesis in a Human

DTIC Science & Technology

2015-12-01

cluster of the WFMA. Electrode current flows between the micro-(working) electrode and a longer large-area counter electrode, using either...Biomed Eng 44(10):931-9. McCreery DB, Yuen TGH, Agnew, WF, Bullara LA (2000). Chronic microstimulation in the feline ventral cochlear nucleus
Activity-dependent formation of a vesicular inhibitory amino acid transporter gradient in the superior olivary complex of NMRI mice.

PubMed

Ebbers, Lena; Weber, Maren; Nothwang, Hans Gerd

2017-10-26

In the mammalian superior olivary complex (SOC), synaptic inhibition contributes to the processing of binaural sound cues important for sound localization. Previous analyses demonstrated a tonotopic gradient for postsynaptic proteins mediating inhibitory neurotransmission in the lateral superior olive (LSO), a major nucleus of the SOC. To probe, whether a presynaptic molecular gradient exists as well, we investigated immunoreactivity against the vesicular inhibitory amino acid transporter (VIAAT) in the mouse auditory brainstem. Immunoreactivity against VIAAT revealed a gradient in the LSO and the superior paraolivary nucleus (SPN) of NMRI mice, with high expression in the lateral, low frequency processing limb and low expression in the medial, high frequency processing limb of both nuclei. This orientation is opposite to the previously reported gradient of glycine receptors in the LSO. Other nuclei of the SOC showed a uniform distribution of VIAAT-immunoreactivity. No gradient was observed for the glycine transporter GlyT2 and the neuronal protein NeuN. Formation of the VIAAT gradient was developmentally regulated and occurred around hearing-onset between postnatal days 8 and 16. Congenital deaf Claudin14 -/- mice bred on an NMRI background showed a uniform VIAAT-immunoreactivity in the LSO, whereas cochlear ablation in NMRI mice after hearing-onset did not affect the gradient. Additional analysis of C57Bl6/J, 129/SvJ and CBA/J mice revealed a strain-specific formation of the gradient. Our results identify an activity-regulated gradient of VIAAT in the SOC of NRMI mice. Its absence in other mouse strains adds a novel layer of strain-specific features in the auditory system, i.e. tonotopic organization of molecular gradients. This calls for caution when comparing data from different mouse strains frequently used in studies involving transgenic animals. The presence of strain-specific differences offers the possibility of genetic mapping to identify molecular factors involved in activity-dependent developmental processes in the auditory system. This would provide an important step forward concerning improved auditory rehabilitation in cases of congenital deafness.
Octopus Cells in the Posteroventral Cochlear Nucleus Provide the Main Excitatory Input to the Superior Paraolivary Nucleus

PubMed Central

Felix II, Richard A.; Gourévitch, Boris; Gómez-Álvarez, Marcelo; Leijon, Sara C. M.; Saldaña, Enrique; Magnusson, Anna K.

2017-01-01

Auditory streaming enables perception and interpretation of complex acoustic environments that contain competing sound sources. At early stages of central processing, sounds are segregated into separate streams representing attributes that later merge into acoustic objects. Streaming of temporal cues is critical for perceiving vocal communication, such as human speech, but our understanding of circuits that underlie this process is lacking, particularly at subcortical levels. The superior paraolivary nucleus (SPON), a prominent group of inhibitory neurons in the mammalian brainstem, has been implicated in processing temporal information needed for the segmentation of ongoing complex sounds into discrete events. The SPON requires temporally precise and robust excitatory input(s) to convey information about the steep rise in sound amplitude that marks the onset of voiced sound elements. Unfortunately, the sources of excitation to the SPON and the impact of these inputs on the behavior of SPON neurons have yet to be resolved. Using anatomical tract tracing and immunohistochemistry, we identified octopus cells in the contralateral cochlear nucleus (CN) as the primary source of excitatory input to the SPON. Cluster analysis of miniature excitatory events also indicated that the majority of SPON neurons receive one type of excitatory input. Precise octopus cell-driven onset spiking coupled with transient offset spiking make SPON responses well-suited to signal transitions in sound energy contained in vocalizations. Targets of octopus cell projections, including the SPON, are strongly implicated in the processing of temporal sound features, which suggests a common pathway that conveys information critical for perception of complex natural sounds. PMID:28620283
Acoustic Overexposure Increases the Expression of VGLUT-2 Mediated Projections from the Lateral Vestibular Nucleus to the Dorsal Cochlear Nucleus

PubMed Central

Barker, Matthew; Solinski, Hans Jürgen; Hashimoto, Haruka; Tagoe, Thomas; Pilati, Nadia; Hamann, Martine

2012-01-01

The dorsal cochlear nucleus (DCN) is a first relay of the central auditory system as well as a site for integration of multimodal information. Vesicular glutamate transporters VGLUT-1 and VGLUT-2 selectively package glutamate into synaptic vesicles and are found to have different patterns of organization in the DCN. Whereas auditory nerve fibers predominantly co-label with VGLUT-1, somatosensory inputs predominantly co-label with VGLUT-2. Here, we used retrograde and anterograde transport of fluorescent conjugated dextran amine (DA) to demonstrate that the lateral vestibular nucleus (LVN) exhibits ipsilateral projections to both fusiform and deep layers of the rat DCN. Stimulating the LVN induced glutamatergic synaptic currents in fusiform cells and granule cell interneurones. We combined the dextran amine neuronal tracing method with immunohistochemistry and showed that labeled projections from the LVN are co-labeled with VGLUT-2 by contrast to VGLUT-1. Wistar rats were exposed to a loud single tone (15 kHz, 110 dB SPL) for 6 hours. Five days after acoustic overexposure, the level of expression of VGLUT-1 in the DCN was decreased whereas the level of expression of VGLUT-2 in the DCN was increased including terminals originating from the LVN. VGLUT-2 mediated projections from the LVN to the DCN are likely to play a role in the head position in response to sound. Amplification of VGLUT-2 expression after acoustic overexposure could be a compensatory mechanism from vestibular inputs in response to hearing loss and to a decrease of VGLUT-1 expression from auditory nerve fibers. PMID:22570693
GaN-based micro-LED arrays on flexible substrates for optical cochlear implants

NASA Astrophysics Data System (ADS)

Goßler, Christian; Bierbrauer, Colin; Moser, Rüdiger; Kunzer, Michael; Holc, Katarzyna; Pletschen, Wilfried; Köhler, Klaus; Wagner, Joachim; Schwaerzle, Michael; Ruther, Patrick; Paul, Oliver; Neef, Jakob; Keppeler, Daniel; Hoch, Gerhard; Moser, Tobias; Schwarz, Ulrich T.

2014-05-01

Currently available cochlear implants are based on electrical stimulation of the spiral ganglion neurons. Optical stimulation with arrays of micro-sized light-emitting diodes (µLEDs) promises to increase the number of distinguishable frequencies. Here, the development of a flexible GaN-based micro-LED array as an optical cochlear implant is reported for application in a mouse model. The fabrication of 15 µm thin and highly flexible devices is enabled by a laser-based layer transfer process of the GaN-LEDs from sapphire to a polyimide-on-silicon carrier wafer. The fabricated 50 × 50 µm2 LEDs are contacted via conducting paths on both p- and n-sides of the LEDs. Up to three separate channels could be addressed. The probes, composed of a linear array of the said µLEDs bonded to the flexible polyimide substrate, are peeled off the carrier wafer and attached to flexible printed circuit boards. Probes with four µLEDs and a width of 230 µm are successfully implanted in the mouse cochlea both in vitro and in vivo. The LEDs emit 60 µW at 1 mA after peel-off, corresponding to a radiant emittance of 6 mW mm-2.
Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow

PubMed Central

Shi, Xiaorui; Zhang, Fei; Urdang, Zachary; Dai, Min; Neng, Lingling; Zhang, Jinhui; Chen, Songlin; Ramamoorthy, Sripriya; Nuttall, Alfred L.

2014-01-01

Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions. PMID:24780131

A Chimera Analysis of Prestin Knockout Mice

PubMed Central

Cheatham, Mary Ann; Low-Zeddies, Sharon; Naik, Khurram; Edge, Roxanne; Zheng, Jing; Anderson, Charles T.; Dallos, Peter

2009-01-01

A chimera is a genetic composite containing a unique mix of cells derived from more than one zygote. This mouse model allows one to learn how cells of contrasting genotype functionally interact in vivo. Here we investigate the effect that different proportions of prestin-containing outer hair cells (OHC) have on cochlear amplification. In order to address this issue, we developed a prestin chimeric mouse in which both ROSA26 wildtype (WT) and prestin knockout (KO) genotypes are present in a single cochlea. The WT ROSA26 mice express a cell marker, allowing one to identify cells originating from the WT genome. Examination of cochlear tissue indicated that prestin chimeric mice demonstrate a mosaic in which mutant and normal OHCs interleave along the cochlear partition, similar to all other chimeric mouse models. The anatomical distribution of prestin-containing OHCs was compared with physiological data including thresholds and tuning curves for the compound action potential (CAP) recorded in anesthetized mice. Analysis of these measures did not reveal mixed phenotypes in which the distribution of prestin-containing OHCs impacted sensitivity and frequency selectivity to different degrees. However, by reducing the number of prestin-containing OHCs, phenotypes intermediate between WT and KO response patterns were obtained. Accordingly, we demonstrate a proportional reduction in sensitivity and in the tip length of CAP tuning curves as the number of OHCs derived from the KO genome increases, i.e., genotype ratio and phenotype are closely related. PMID:19776286
Basilar membrane vibration after targeted removal of the third row of OHCs and Deiters cells

NASA Astrophysics Data System (ADS)

Xia, Anping; Udagawa, Tomokatsu; Raphael, Patrick D.; Cheng, Alan G.; Steele, Charles R.; Applegate, Brian E.; Oghalai, John S.

2018-05-01

The mammalian cochlea has three rows of outer hair cells (OHCs) that amplify the basilar membrane (BM) traveling wave with high gain and exquisite sharpness. However, it is unclear why three rows of OHCs are needed to achieve this. We used a novel transgenic mouse with the diphtheria toxin receptor in Lgr5-positive cells (Lgr5DTR-EGFP/+ mouse) that allowed us to ablate the third row of OHCs and Deiters cells (D) in adulthood via DT injection, after normal cochlear function had developed. We then used volumetric optical coherence tomography (VOCTV) to investigate the impacts of this manipulation of cochlear amplification in the apical turn. As expected, Lgr5DTR-EGFP/+ control mice had sharply-tuned vibratory responses. However, Lgr5DTR-EGFP/+ mice had broad tuning with a 20 dB increase in vibratory thresholds. The Q10dB was ˜1 in Lgr5DTR-EGFP/+ mice, whereas it was ˜3 in control mice. The characteristic frequency was lower in Lgr5DTR-EGFP/+ mice compared to controls (7.5 vs. 9.0 kHz). The gain of cochlear amplification was substantially lower in Lgr5DTR-EGFP/+ mice compared to controls (22 vs. 50). In the post-mortem period, the vibratory responses in Lgr5DTR-EGFP/+ mice were identical to controls. Together, these results demonstrate the substantial importance of the third row of OHCs and Deiters cells to normal cochlear amplification.
Evidence for vestibular regulation of autonomic functions in a mouse genetic model

NASA Technical Reports Server (NTRS)

Murakami, Dean M.; Erkman, Linda; Hermanson, Ola; Rosenfeld, Michael G.; Fuller, Charles A.

2002-01-01

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.
The temporal representation of the delay of dynamic iterated rippled noise with positive and negative gain by single units in the ventral cochlear nucleus.

PubMed

Sayles, Mark; Winter, Ian Michael

2007-09-26

Spike trains were recorded from single units in the ventral cochlear nucleus of the anaesthetised guinea-pig in response to dynamic iterated rippled noise with positive and negative gain. The short-term running waveform autocorrelation functions of these stimuli show peaks at integer multiples of the time-varying delay when the gain is +1, and troughs at odd-integer multiples and peaks at even-integer multiples of the time-varying delay when the gain is -1. In contrast, the short-term autocorrelation of the Hilbert envelope shows peaks at integer multiples of the time-varying delay for both positive and negative gain stimuli. A running short-term all-order interspike interval analysis demonstrates the ability of single units to represent the modulated pitch contour in their short-term interval statistics. For units with low best frequency (approximate < or = 1.1 kHz) the temporal discharge pattern reflected the waveform fine structure regardless of unit classification (Primary-like, Chopper). For higher best frequency units the pattern of response varied according to unit type. Chopper units with best frequency approximate > or = 1.1 kHz responded to envelope modulation; showing no difference between their response to stimuli with positive and negative gain. Primary-like units with best frequencies in the range 1-3 kHz were still able to represent the difference in the temporal fine structure between dynamic rippled noise with positive and negative gain. No unit with a best frequency above 3 kHz showed a response to the temporal fine structure. Chopper units in this high frequency group showed significantly greater representation of envelope modulation relative to primary-like units with the same range of best frequencies. These results show that at the level of the cochlear nucleus there exists sufficient information in the time domain to represent the time-varying pitch associated with dynamic iterated rippled noise.
Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

PubMed Central

León, Alex; Elgueda, Diego; Silva, María A.; Hamamé, Carlos M.; Delano, Paul H.

2012-01-01

Background The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. Conclusions/Significance These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects suggests that there are at least two functional pathways from the auditory cortex to the cochlea. PMID:22558383
Developmental Emergence of Phenotypes in the Auditory Brainstem Nuclei of Fmr1 Knockout Mice

PubMed Central

Rotschafer, Sarah E.

2017-01-01

Abstract Fragile X syndrome (FXS), the most common monogenic cause of autism, is often associated with hypersensitivity to sound. Several studies have shown abnormalities in the auditory brainstem in FXS; however, the emergence of these auditory phenotypes during development has not been described. Here, we investigated the development of phenotypes in FXS model [Fmr1 knockout (KO)] mice in the ventral cochlear nucleus (VCN), medial nucleus of the trapezoid body (MNTB), and lateral superior olive (LSO). We studied features of the brainstem known to be altered in FXS or Fmr1 KO mice, including cell size and expression of markers for excitatory (VGLUT) and inhibitory (VGAT) synapses. We found that cell size was reduced in the nuclei with different time courses. VCN cell size is normal until after hearing onset, while MNTB and LSO show decreases earlier. VGAT expression was elevated relative to VGLUT in the Fmr1 KO mouse MNTB by P6, before hearing onset. Because glial cells influence development and are altered in FXS, we investigated their emergence in the developing Fmr1 KO brainstem. The number of microglia developed normally in all three nuclei in Fmr1 KO mice, but we found elevated numbers of astrocytes in Fmr1 KO in VCN and LSO at P14. The results indicate that some phenotypes are evident before spontaneous or auditory activity, while others emerge later, and suggest that Fmr1 acts at multiple sites and time points in auditory system development. PMID:29291238
Modeling the effect of channel number and interaction on consonant recognition in a cochlear implant peak-picking strategy.

PubMed

Verschuur, Carl

2009-03-01

Difficulties in speech recognition experienced by cochlear implant users may be attributed both to information loss caused by signal processing and to information loss associated with the interface between the electrode array and auditory nervous system, including cross-channel interaction. The objective of the work reported here was to attempt to partial out the relative contribution of these different factors to consonant recognition. This was achieved by comparing patterns of consonant feature recognition as a function of channel number and presence/absence of background noise in users of the Nucleus 24 device with normal hearing subjects listening to acoustic models that mimicked processing of that device. Additionally, in the acoustic model experiment, a simulation of cross-channel spread of excitation, or "channel interaction," was varied. Results showed that acoustic model experiments were highly correlated with patterns of performance in better-performing cochlear implant users. Deficits to consonant recognition in this subgroup could be attributed to cochlear implant processing, whereas channel interaction played a much smaller role in determining performance errors. The study also showed that large changes to channel number in the Advanced Combination Encoder signal processing strategy led to no substantial changes in performance.
Phase contrast tomography of the mouse cochlea at microfocus x-ray sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bartels, Matthias; Krenkel, Martin; Hernandez, Victor H.

2013-08-19

We present phase contrast x-ray tomography of functional soft tissue within the bony cochlear capsule of mice, carried out at laboratory microfocus sources with well-matched source, detector, geometry, and reconstruction algorithms at spatial resolutions down to 2 μm. Contrast, data quality and resolution enable the visualization of thin membranes and nerve fibers as well as automated segmentation of surrounding bone. By complementing synchrotron radiation imaging techniques, a broad range of biomedical applications becomes possible as demonstrated for optogenetic cochlear implant research.
CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss.

PubMed

Teitz, Tal; Fang, Jie; Goktug, Asli N; Bonga, Justine D; Diao, Shiyong; Hazlitt, Robert A; Iconaru, Luigi; Morfouace, Marie; Currier, Duane; Zhou, Yinmei; Umans, Robyn A; Taylor, Michael R; Cheng, Cheng; Min, Jaeki; Freeman, Burgess; Peng, Junmin; Roussel, Martine F; Kriwacki, Richard; Guy, R Kiplin; Chen, Taosheng; Zuo, Jian

2018-04-02

Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration-approved drugs to prevent or treat it. We screened 4,385 small molecules in a cochlear cell line and identified 10 compounds that protected against cisplatin toxicity in mouse cochlear explants. Among them, kenpaullone, an inhibitor of multiple kinases, including cyclin-dependent kinase 2 (CDK2), protected zebrafish lateral-line neuromasts from cisplatin toxicity and, when delivered locally, protected adult mice and rats against cisplatin- and noise-induced hearing loss. CDK2-deficient mice displayed enhanced resistance to cisplatin toxicity in cochlear explants and to cisplatin- and noise-induced hearing loss in vivo. Mechanistically, we showed that kenpaullone directly inhibits CDK2 kinase activity and reduces cisplatin-induced mitochondrial production of reactive oxygen species, thereby enhancing cell survival. Our experiments have revealed the proapoptotic function of CDK2 in postmitotic cochlear cells and have identified promising therapeutics for preventing hearing loss. © 2018 Teitz et al.
CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss

PubMed Central

Teitz, Tal; Fang, Jie; Goktug, Asli N.; Bonga, Justine D.; Diao, Shiyong; Iconaru, Luigi; Morfouace, Marie; Currier, Duane; Zhou, Yinmei; Umans, Robyn A.; Taylor, Michael R.; Cheng, Cheng; Peng, Junmin; Roussel, Martine F.; Kriwacki, Richard; Guy, R. Kiplin; Chen, Taosheng

2018-01-01

Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration–approved drugs to prevent or treat it. We screened 4,385 small molecules in a cochlear cell line and identified 10 compounds that protected against cisplatin toxicity in mouse cochlear explants. Among them, kenpaullone, an inhibitor of multiple kinases, including cyclin-dependent kinase 2 (CDK2), protected zebrafish lateral-line neuromasts from cisplatin toxicity and, when delivered locally, protected adult mice and rats against cisplatin- and noise-induced hearing loss. CDK2-deficient mice displayed enhanced resistance to cisplatin toxicity in cochlear explants and to cisplatin- and noise-induced hearing loss in vivo. Mechanistically, we showed that kenpaullone directly inhibits CDK2 kinase activity and reduces cisplatin-induced mitochondrial production of reactive oxygen species, thereby enhancing cell survival. Our experiments have revealed the proapoptotic function of CDK2 in postmitotic cochlear cells and have identified promising therapeutics for preventing hearing loss. PMID:29514916
Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders.

PubMed

Matrov, Denis; Kaart, Tanel; Lanfumey, Laurence; Maldonado, Rafael; Sharp, Trevor; Tordera, Rosa M; Kelly, Paul A; Deakin, Bill; Harro, Jaanus

2018-06-07

The psychopathology of depression is highly complex and the outcome of studies on animal models is divergent. In order to find brain regions that could be metabolically distinctively active across a variety of mouse depression models and to compare the interconnectivity of brain regions of wild-type and such genetically modified mice, histochemical mapping of oxidative metabolism was performed by the measurement of cytochrome oxidase activity. We included mice with the heterozygous knockout of the vesicular glutamate transporter (VGLUT 1 -/+ ), full knockout of the cannabinoid 1 receptor (CB1 -/- ), an anti-sense knockdown of the glucocorticoid receptor (GRi) and overexpression of the human 5-hydroxytryptamine transporter (h5-HTT). Altogether 76 mouse brains were studied to measure oxidative metabolism in one hundred brain regions, and the obtained dataset was submitted to a variety of machine learning algorithms and multidimensional scaling. Overall, the top brain regions having the largest contribution to classification into depression model were the lateroanterior hypothalamic nucleus, the anterior part of the basomedial amygdaloid nucleus, claustrum, the suprachiasmatic nucleus, the ventromedial hypothalamic nucleus, and the anterior hypothalamic area. In terms of the patterns of inter-regional relationship between wild-type and genetically modified mice there was little overall difference, while the most deviating brain regions were cortical amygdala and ventrolateral and ventral posteromedial thalamic nuclei. The GRi mice that most clearly differed from their controls exhibited deviation of connectivity for a number of brain regions, such as ventrolateral thalamic nucleus, the intermediate part of the lateral septal nucleus, the anteriodorsal part of the medial amygdaloid nucleus, the medial division of the central amygdaloid nucleus, ventral pallidum, nucleus of the vertical limb of the diagonal band, anteroventral parts of the thalamic nucleus and parts of the bed nucleus of the stria terminalis. Conclusively, the GRi mouse model was characterized by changes in the functional connectivity of the extended amygdala and stress response circuits. Copyright © 2018 Elsevier B.V. All rights reserved.
Audiological outcomes of cochlear implantation in Waardenburg Syndrome.

PubMed

Magalhães, Ana Tereza de Matos; Samuel, Paola Angélica; Goffi-Gomez, Maria Valeria Schimdt; Tsuji, Robinson Koji; Brito, Rubens; Bento, Ricardo Ferreira

2013-07-01

The most relevant clinical symptom in Waardenburg syndrome is profound bilateral sensorioneural hearing loss. To characterize and describe hearing outcomes after cochlear implantation in patients with Waardenburg syndrome to improve preoperative expectations. This was an observational and retrospective study of a series of cases. Children who were diagnosed with Waardenburg syndrome and who received a multichannel cochlear implant between March 1999 and July 2012 were included in the study. Intraoperative neural response telemetry, hearing evaluation, speech perception, and speech production data before and after surgery were assessed. During this period, 806 patients received a cochlear implant and 10 of these (1.2%) were diagnosed with Waardenburg syndrome. Eight of the children received a Nucleus 24(®) implant and 1 child and 1 adult received a DigiSonic SP implant. The mean age at implantation was 44 months among the children. The average duration of use of a cochlear implant at the time of the study was 43 months. Intraoperative neural responses were present in all cases. Patients who could use the speech processor effectively had a pure tone average of 31 dB in free-field conditions. In addition, the MUSS and MAIS questionnaires revealed improvements in speech perception and production. Four patients did not have a good outcome, which might have been associated with ineffective use of the speech processor. Despite the heterogeneity of the group, patients with Waardenburg syndrome who received cochlear implants were found to have hearing thresholds that allowed access to speech sounds. However, patients who received early intervention and rehabilitation showed better evolution of auditory perception.
Expression of a serine protease (motopsin PRSS12) mRNA in the mouse brain: in situ hybridization histochemical study.

PubMed

Iijima, N; Tanaka, M; Mitsui, S; Yamamura, Y; Yamaguchi, N; Ibata, Y

1999-03-20

Serine proteases are considered to play several important roles in the brain. In an attempt to find novel brain-specific serine proteases (BSSPs), motopsin (PRSS-12) was cloned from a mouse brain cDNA library by polymerase chain reaction (PCR). Northern blot analysis demonstrated that the postnatal 10-day mouse brain contained the most amount of motopsin mRNA. At this developmental stage, in situ hybridization histochemistry showed that motopsin mRNA was specifically expressed in the following regions: cerebral cortical layers II/III, V and VIb, endopiriform cortex and the limbic system, particularly in the CA1 region of the hippocampal formation. In addition, in the brainstem, the oculomotor nucleus, trochlear nucleus, mecencephalic and motor nuclei of trigeminal nerve (N), abducens nucleus, facial nucleus, nucleus of the raphe pontis, dorsoral motor nucleus of vagal N, hypoglossal nucleus and ambiguus nucleus showed motopsin mRNA expression. Expression was also found in the anterior horn of the spinal cord. The above findings strongly suggest that neurons in almost all motor nuclei, particularly in the brainstem and spinal cord, express motopsin mRNA, and that motopsin seems to have a close relation to the functional role of efferent neurons. Copyright 1999 Elsevier Science B.V.
Slit/Robo Signaling Mediates Spatial Positioning of Spiral Ganglion Neurons during Development of Cochlear Innervation

PubMed Central

Wang, Sheng-zhi; Ibrahim, Leena A.; Kim, Young J.; Gibson, Daniel A.; Leung, Haiwen C.; Yuan, Wei; Zhang, Ke K.; Tao, Huizhong W.

2013-01-01

During the development of periphery auditory circuits, spiral ganglion neurons (SGNs) extend their neurites to innervate cochlear hair cells (HCs) with their soma aggregated into a cluster spatially segregated from the cochlear sensory epithelium. The molecular mechanisms underlying this spatial patterning remain unclear. In this study, in situ hybridization in the mouse cochlea suggests that Slit2 and its receptor, Robo1/2, exhibit apparently complementary expression patterns in the spiral ganglion and its nearby region, the spiral limbus. In Slit2 and Robo1/2 mutants, the spatial restriction of SGNs was disrupted. Mispositioned SGNs were found to scatter in the space between the cochlear epithelium and the main body of spiral ganglion, and the neurites of mispositioned SGNs were misrouted and failed to innervate HCs. Furthermore, in Robo1/2 mutants, SGNs were displaced toward the cochlear epithelium as an entirety. Examination of different embryonic stages in the mutants revealed that the mispositioning of SGNs was due to a progressive displacement to ectopic locations after their initial normal settlement at an earlier stage. Our results suggest that Slit/Robo signaling imposes a restriction force on SGNs to ensure their precise positioning for correct SGN-HC innervations. PMID:23884932
Adult Plasticity in the Subcortical Auditory Pathway of the Maternal Mouse

PubMed Central

Miranda, Jason A.; Shepard, Kathryn N.; McClintock, Shannon K.; Liu, Robert C.

2014-01-01

Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system – motherhood – is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered. PMID:24992362
Adult plasticity in the subcortical auditory pathway of the maternal mouse.

PubMed

Miranda, Jason A; Shepard, Kathryn N; McClintock, Shannon K; Liu, Robert C

2014-01-01

Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.
Multicenter Clinical Trial of the Nucleus® Hybrid™ S8 Cochlear Implant: Final Outcomes

PubMed Central

Gantz, Bruce J; Dunn, Camille; Oleson, Jacob; Hansen, Marlan; Parkinson, Aaron; Turner, Christopher

2015-01-01

Objective The concept expanding electrical speech processing to those with more residual acoustic hearing with a less invasive shorter cochlear implant has been ongoing since 1999. A multi-center study of the Nucleus Hybrid S8 CI took place between 2002–11. This report describes the final outcomes of this clinical trial. Study Design Multi-Center longitudinal single subject design Methods Eighty-seven subjects received a Nucleus® Hybrid™ S8 implant in their poorer ear. Speech perception in quiet (CNC words) and in noise (BKB-SIN) was collected pre- and post-operatively at 3, 6, and 12 months. Subjective questionnaire data using the APHAB was also collected. Results Some level of hearing preservation was accomplished in 98% subjects with 90% maintaining a functional low-frequency pure-tone average (LFPTA) at initial activation. By 12 months, 5 subjects had total hearing loss and 80% of subjects maintained functional hearing. CNC words demonstrated that 82.5% and 87.5% of subjects had significant improvements in the Hybrid and Combined conditions. The majority of had improvements with BKB-SIN. Results also indicated that as long as subjects maintained at least a severe LFPTA, there was significant improvement in speech understanding. Furthermore, all subjects reported positive improvements in hearing in three of the 4 subscales of the APHAB. Conclusion The concept of hybrid speech processing has significant advantages for subjects with residual low-frequency hearing. In this study, the Nucleus® Hybrid™ S8 provided improved word understanding in quiet and noise. Additionally, there appears to be stability of the residual hearing after initial activation of the device. Level of evidence 2c PMID:26756395
Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow.

PubMed

Shi, Xiaorui; Zhang, Fei; Urdang, Zachary; Dai, Min; Neng, Lingling; Zhang, Jinhui; Chen, Songlin; Ramamoorthy, Sripriya; Nuttall, Alfred L

2014-07-01

Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions. Copyright © 2014 Elsevier B.V. All rights reserved.
Concurrent gradients of ribbon volume and AMPA-receptor patch volume in cochlear afferent synapses on gerbil inner hair cells.

PubMed

Zhang, Lichun; Engler, Sina; Koepcke, Lena; Steenken, Friederike; Köppl, Christine

2018-07-01

The Mongolian gerbil is a classic animal model for age-related hearing loss. As a prerequisite for studying age-related changes, we characterized cochlear afferent synaptic morphology in young adult gerbils, using immunolabeling and quantitative analysis of confocal microscopic images. Cochlear wholemounts were triple-labeled with a hair-cell marker, a marker of presynaptic ribbons, and a marker of postsynaptic AMPA-type glutamate receptors. Seven cochlear positions covering an equivalent frequency range from 0.5 - 32 kHz were evaluated. The spatial positions of synapses were determined in a coordinate system with reference to their individual inner hair cell. Synapse numbers confirmed previous reports for gerbils (on average, 20-22 afferents per inner hair cell). The volumes of presynaptic ribbons and postsynaptic glutamate receptor patches were positively correlated: larger ribbons associated with larger receptor patches and smaller ribbons with smaller patches. Furthermore, the volumes of both presynaptic ribbons and postsynaptic receptor patches co-varied along the modiolar-pillar and the longitudinal axes of their hair cell. The gradients in ribbon volume are consistent with previous findings in cat, guinea pig, mouse and rat and further support a role in differentiating the physiological properties of type I afferents. However, the positive correlation between the volumes of pre- and postsynaptic elements in the gerbil is different to the opposing gradients found in the mouse, suggesting species-specific differences in the postsynaptic AMPA receptors that are unrelated to the fundamental classes of type I afferents. Copyright © 2018 Elsevier B.V. All rights reserved.
Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea.

PubMed

Hossain, Waheeda A; Antic, Srdjan D; Yang, Yang; Rasband, Matthew N; Morest, D Kent

2005-07-20

The origin of the action potential in the cochlea has been a long-standing puzzle. Because voltage-dependent Na+ (Nav) channels are essential for action potential generation, we investigated the detailed distribution of Nav1.6 and Nav1.2 in the cochlear ganglion, cochlear nerve, and organ of Corti, including the type I and type II ganglion cells. In most type I ganglion cells, Nav1.6 was present at the first nodes flanking the myelinated bipolar cell body and at subsequent nodes of Ranvier. In the other ganglion cells, including type II, Nav1.6 clustered in the initial segments of both of the axons that flank the unmyelinated bipolar ganglion cell bodies. In the organ of Corti, Nav1.6 was localized in the short segments of the afferent axons and their sensory endings beneath each inner hair cell. Surprisingly, the outer spiral fibers and their sensory endings were well labeled beneath the outer hair cells over their entire trajectory. In contrast, Nav1.2 in the organ of Corti was localized to the unmyelinated efferent axons and their endings on the inner and outer hair cells. We present a computational model illustrating the potential role of the Nav channel distribution described here. In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion. Together, these results suggest that distinct Nav channels generate and regenerate action potentials at multiple sites along the cochlear ganglion cells and nerve fibers, including the afferent endings, ganglionic initial segments, and nodes of Ranvier.

Bioinformatic Integration of Molecular Networks and Major Pathways Involved in Mice Cochlear and Vestibular Supporting Cells.

PubMed

Requena, Teresa; Gallego-Martinez, Alvaro; Lopez-Escamez, Jose A

2018-01-01

Background : Cochlear and vestibular epithelial non-hair cells (ENHCs) are the supporting elements of the cellular architecture in the organ of Corti and the vestibular neuroepithelium in the inner ear. Intercellular and cell-extracellular matrix interactions are essential to prevent an abnormal ion redistribution leading to hearing and vestibular loss. The aim of this study is to define the main pathways and molecular networks in the mouse ENHCs. Methods : We retrieved microarray and RNA-seq datasets from mouse epithelial sensory and non-sensory cells from gEAR portal (http://umgear.org/index.html) and obtained gene expression fold-change between ENHCs and non-epithelial cells (NECs) against HCs for each gene. Differentially expressed genes (DEG) with a log2 fold change between 1 and -1 were discarded. The remaining genes were selected to search for interactions using Ingenuity Pathway Analysis and STRING platform. Specific molecular networks for ENHCs in the cochlea and the vestibular organs were generated and significant pathways were identified. Results : Between 1723 and 1559 DEG were found in the mouse cochlear and vestibular tissues, respectively. Six main pathways showed enrichment in the supporting cells in both tissues: (1) "Inhibition of Matrix Metalloproteases"; (2) "Calcium Transport I"; (3) "Calcium Signaling"; (4) "Leukocyte Extravasation Signaling"; (5) "Signaling by Rho Family GTPases"; and (6) "Axonal Guidance Si". In the mouse cochlea, ENHCs showed a significant enrichment in 18 pathways highlighting "axonal guidance signaling (AGS)" ( p = 4.37 × 10 -8 ) and "RhoGDI Signaling" ( p = 3.31 × 10 -8 ). In the vestibular dataset, there were 20 enriched pathways in ENHCs, the most significant being "Leukocyte Extravasation Signaling" ( p = 8.71 × 10 -6 ), "Signaling by Rho Family GTPases" ( p = 1.20 × 10 -5 ) and "Calcium Signaling" ( p = 1.20 × 10 -5 ). Among the top ranked networks, the most biologically significant network contained the "auditory and vestibular system development and function" terms. We also found 108 genes showing tonotopic gene expression in the cochlear ENHCs. Conclusions : We have predicted the main pathways and molecular networks for ENHCs in the organ of Corti and vestibular neuroepithelium. These pathways will facilitate the design of molecular maps to select novel candidate genes for hearing or vestibular loss to conduct functional studies.
Three-Dimensional Imaging of the Mouse Organ of Corti Cytoarchitecture for Mechanical Modeling

NASA Astrophysics Data System (ADS)

Puria, Sunil; Hartman, Byron; Kim, Jichul; Oghalai, John S.; Ricci, Anthony J.; Liberman, M. Charles

2011-11-01

Cochlear models typically use continuous anatomical descriptions and homogenized parameters based on two-dimensional images for describing the organ of Corti. To produce refined models based more closely on the actual cochlear cytoarchitecture, three-dimensional morphometric parameters of key mechanical structures are required. Towards this goal, we developed and compared three different imaging methods: (1) A fixed cochlear whole-mount preparation using the fluorescent dye Cellmask®, which is a molecule taken up by cell membranes and clearly delineates Deiters' cells, outer hair cells, and the phalangeal process, imaged using confocal microscopy; (2) An in situ fixed preparation with hair cells labeled using anti-prestin and supporting structures labeled using phalloidin, imaged using two-photon microscopy; and (3) A membrane-tomato (mT) mouse with fluorescent proteins expressed in all cell membranes, which enables two-photon imaging of an in situ live preparation with excellent visualization of the organ of Corti. Morphometric parameters including lengths, diameters, and angles, were extracted from 3D cellular surface reconstructions of the resulting images. Preliminary results indicate that the length of the phalangeal processes decreases from the first (inner most) to third (outer most) row of outer hair cells, and that their length also likely varies from base to apex and across species.
Changes in cochlear blood flow in mice due to loud sound exposure measured with Doppler optical microangiography and laser Doppler flowmetry.

PubMed

Reif, Roberto; Zhi, Zhongwei; Dziennis, Suzan; Nuttall, Alfred L; Wang, Ruikang K

2013-10-01

In this work we determined the contributions of loud sound exposure (LSE) on cochlear blood flow (CoBF) in an in vivo anesthetized mouse model. A broadband noise system (20 kHz bandwidth) with an intensity of 119 dB SPL, was used for a period of one hour to produce a loud sound stimulus. Two techniques were used to study the changes in blood flow, a Doppler optical microangiography (DOMAG) system; which can measure the blood flow within individual cochlear vessels, and a laser Doppler flowmetry (LDF) system; which averages the blood flow within a volume (a hemisphere of ~1.5 mm radius) of tissue. Both systems determined that the blood flow within the cochlea is reduced due to the LSE stimulation.
Speech Recognition with the Advanced Combination Encoder and Transient Emphasis Spectral Maxima Strategies in Nucleus 24 Recipients

ERIC Educational Resources Information Center

Holden, Laura K.; Vandali, Andrew E.; Skinner, Margaret W.; Fourakis, Marios S.; Holden, Timothy A.

2005-01-01

One of the difficulties faced by cochlear implant (CI) recipients is perception of low-intensity speech cues. A. E. Vandali (2001) has developed the transient emphasis spectral maxima (TESM) strategy to amplify short-duration, low-level sounds. The aim of the present study was to determine whether speech scores would be significantly higher with…
AUDITORY NUCLEI: DISTINCTIVE RESPONSE PATTERNS TO WHITE NOISE AND TONES IN UNANESTHETIZED CATS.

PubMed

GALIN, D

1964-10-09

Electrical responses to "white" noise and tonal stimuli were recorded from unanesthetized cats with permanently implanted bipolar electrodes. The cochlear nucleus, inferior colliculus, and medial geniculate each showed distinctive patterns of evoked activity. White noise and tones produced qualitatively different types of response. A decrease in activity characterized the response of the inferior colliculus to tonal stimuli.
Auditory pathways: anatomy and physiology.

PubMed

Pickles, James O

2015-01-01

This chapter outlines the anatomy and physiology of the auditory pathways. After a brief analysis of the external, middle ears, and cochlea, the responses of auditory nerve fibers are described. The central nervous system is analyzed in more detail. A scheme is provided to help understand the complex and multiple auditory pathways running through the brainstem. The multiple pathways are based on the need to preserve accurate timing while extracting complex spectral patterns in the auditory input. The auditory nerve fibers branch to give two pathways, a ventral sound-localizing stream, and a dorsal mainly pattern recognition stream, which innervate the different divisions of the cochlear nucleus. The outputs of the two streams, with their two types of analysis, are progressively combined in the inferior colliculus and onwards, to produce the representation of what can be called the "auditory objects" in the external world. The progressive extraction of critical features in the auditory stimulus in the different levels of the central auditory system, from cochlear nucleus to auditory cortex, is described. In addition, the auditory centrifugal system, running from cortex in multiple stages to the organ of Corti of the cochlea, is described. © 2015 Elsevier B.V. All rights reserved.
Auditory brainstem responses of CBA/J mice with neonatal conductive hearing losses and treatment with GM1 ganglioside.

PubMed

Money, M K; Pippin, G W; Weaver, K E; Kirsch, J P; Webster, D B

1995-07-01

Exogenous administration of GM1 ganglioside to CBA/J mice with a neonatal conductive hearing loss ameliorates the atrophy of spiral ganglion neurons, ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. The present investigation demonstrates the extent of a conductive loss caused by atresia and tests the hypothesis that GM1 ganglioside treatment will ameliorate the conductive hearing loss. Auditory brainstem responses were recorded from four groups of seven mice each: two groups received daily subcutaneous injections of saline (one group had normal hearing; the other had a conductive hearing loss); the other two groups received daily subcutaneous injections of GM1 ganglioside (one group had normal hearing; the other had a conductive hearing loss). In mice with a conductive loss, decreases in hearing sensitivity were greatest at high frequencies. The decreases were determined by comparing mean ABR thresholds of the conductive loss mice with those of normal hearing mice. The conductive hearing loss induced in the mice in this study was similar to that seen in humans with congenital aural atresias. GM1 ganglioside treatment had no significant effect on ABR wave I thresholds or latencies in either group.
Awake craniotomy for assisting placement of auditory brainstem implant in NF2 patients.

PubMed

Zhou, Qiangyi; Yang, Zhijun; Wang, Zhenmin; Wang, Bo; Wang, Xingchao; Zhao, Chi; Zhang, Shun; Wu, Tao; Li, Peng; Li, Shiwei; Zhao, Fu; Liu, Pinan

2018-06-01

Auditory brainstem implants (ABIs) may be the only opportunity for patients with NF2 to regain some sense of hearing sensation. However, only a very small number of individuals achieved open-set speech understanding and high sentence scores. Suboptimal placement of the ABI electrode array over the cochlear nucleus may be one of main factors for poor auditory performance. In the current study, we present a method of awake craniotomy to assist with ABI placement. Awake surgery and hearing test via the retrosigmoid approach were performed for vestibular schwannoma resections and auditory brainstem implantations in four patients with NF2. Auditory outcomes and complications were assessed postoperatively. Three of 4 patients who underwent awake craniotomy during ABI surgery received reproducible auditory sensations intraoperatively. Satisfactory numbers of effective electrodes, threshold levels and distinct pitches were achieved in the wake-up hearing test. In addition, relatively few electrodes produced non-auditory percepts. There was no serious complication attributable to the ABI or awake craniotomy. It is safe and well tolerated for neurofibromatosis type 2 (NF2) patients using awake craniotomy during auditory brainstem implantation. This method can potentially improve the localization accuracy of the cochlear nucleus during surgery.
Effects of intense tone exposure on choline acetyltransferase activity in the hamster cochlear nucleus.

PubMed

Jin, Yong-Ming; Godfrey, Donald A; Wang, Jie; Kaltenbach, James A

2006-01-01

Choline acetyltransferase (ChAT) activity has been mapped in the cochlear nucleus (CN) of control hamsters and hamsters that had been exposed to an intense tone. ChAT activity in most CN regions of hamsters was only a third or less of the activity in rat CN, but in granular regions ChAT activity was similar in both species. Eight days after intense tone exposure, average ChAT activity increased on the tone-exposed side as compared to the opposite side, by 74% in the anteroventral CN (AVCN), by 55% in the granular region dorsolateral to it, and by 74% in the deep layer of the dorsal CN (DCN). In addition, average ChAT activity in the exposed-side AVCN and fusiform soma layer of DCN was higher than in controls, by 152% and 67%, respectively. Two months after exposure, average ChAT activity was still 53% higher in the exposed-side deep layer of DCN as compared to the opposite side. Increased ChAT activity after intense tone exposure may indicate that this exposure leads to plasticity of descending cholinergic innervation to the CN, which might affect spontaneous activity in the DCN that has been associated with tinnitus.
Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus.

PubMed

Li, Shuang; Choi, Veronica; Tzounopoulos, Thanos

2013-06-11

Tinnitus, the perception of phantom sound, is often a debilitating condition that affects many millions of people. Little is known, however, about the molecules that participate in the induction of tinnitus. In brain slices containing the dorsal cochlear nucleus, we reveal a tinnitus-specific increase in the spontaneous firing rate of principal neurons (hyperactivity). This hyperactivity is observed only in noise-exposed mice that develop tinnitus and only in the dorsal cochlear nucleus regions that are sensitive to high frequency sounds. We show that a reduction in Kv7.2/3 channel activity is essential for tinnitus induction and for the tinnitus-specific hyperactivity. This reduction is due to a shift in the voltage dependence of Kv7 channel activation to more positive voltages. Our in vivo studies demonstrate that a pharmacological manipulation that shifts the voltage dependence of Kv7 to more negative voltages prevents the development of tinnitus. Together, our studies provide an important link between the biophysical properties of the Kv7 channel and the generation of tinnitus. Moreover, our findings point to previously unknown biological targets for designing therapeutic drugs that may prevent the development of tinnitus in humans.
Speech Recognition of Bimodal Cochlear Implant Recipients Using a Wireless Audio Streaming Accessory for the Telephone.

PubMed

Wolfe, Jace; Morais, Mila; Schafer, Erin

2016-02-01

The goals of the present investigation were (1) to evaluate recognition of recorded speech presented over a mobile telephone for a group of adult bimodal cochlear implant users, and (2) to measure the potential benefits of wireless hearing assistance technology (HAT) for mobile telephone speech recognition using bimodal stimulation (i.e., a cochlear implant in one ear and a hearing aid on the other ear). A three-by-two-way repeated measures design was used to evaluate mobile telephone sentence-recognition performance differences obtained in quiet and in noise with and without the wireless HAT accessory coupled to the hearing aid alone, CI sound processor alone, and in the bimodal condition. Outpatient cochlear implant clinic. Sixteen bimodal users with Nucleus 24, Freedom, CI512, or CI422 cochlear implants participated in this study. Performance was measured with and without the use of a wireless HAT for the telephone used with the hearing aid alone, CI alone, and bimodal condition. CNC word recognition in quiet and in noise with and without the use of a wireless HAT telephone accessory in the hearing aid alone, CI alone, and bimodal conditions. Results suggested that the bimodal condition gave significantly better speech recognition on the mobile telephone with the wireless HAT. A wireless HAT for the mobile telephone provides bimodal users with significant improvement in word recognition in quiet and in noise over the mobile telephone.
Determination of the position of nucleus cochlear implant electrodes in the inner ear.

PubMed

Skinner, M W; Ketten, D R; Vannier, M W; Gates, G A; Yoffie, R L; Kalender, W A

1994-09-01

Accurate determination of intracochlear electrode position in patients with cochlear implants could provide a basis for detecting migration of the implant and could aid in the selection of stimulation parameters for sound processor programming. New computer algorithms for submillimeter resolution and 3-D reconstruction from spiral computed tomographic (CT) scans now make it possible to accurately determine the position of implanted electrodes within the cochlear canal. The accuracy of these algorithms was tested using an electrode array placed in a phantom model. Measurements of electrode length and interelectrode distance from spiral CT scan reconstructions were in close agreement with those from stereo microscopy. Although apparent electrode width was increased on CT scans due to partial volume averaging, a correction factor was developed for measurements from conventional radiographs and an expanded CT absorption value scale added to detect the presence of platinum electrodes and wires. The length of the cochlear canal was calculated from preoperative spiral CT scans for one patient, and the length of insertion of the electrode array was calculated from her postoperative spiral CT scans. The cross-sectional position of electrodes in relation to the outer bony wall and modiolus was measured and plotted as a function of distance with the electrode width correction applied.
Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear.

PubMed

Kilpatrick, L A; Li, Q; Yang, J; Goddard, J C; Fekete, D M; Lang, H

2011-06-01

Murine models are ideal for studying cochlear gene transfer, as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, because of the small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for the delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAVs) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear, and allows for near-complete preservation of low and middle frequency hearing. In this study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6 and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness.
Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear

PubMed Central

Kilpatrick, Lauren A.; Li, Qian; Yang, John; Goddard, John C; Fekete, Donna M.; Lang, Hainan

2010-01-01

Murine models are ideal for studying cochlear gene transfer as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, due to its small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAV) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear and allows for near-complete preservation of low and middle frequency hearing. In the present study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6, and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus (CMV) promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells (IHCs) were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness. PMID:21209625
Implications of Minimizing Trauma During Conventional Cochlear Implantation

PubMed Central

Carlson, Matthew L.; Driscoll, Colin L. W.; Gifford, René H.; Service, Geoffrey J.; Tombers, Nicole M.; Hughes-Borst, Becky J.; Neff, Brian A.; Beatty, Charles W.

2014-01-01

Objective To describe the relationship between implantation-associated trauma and postoperative speech perception scores among adult and pediatric patients undergoing cochlear implantation using conventional length electrodes and minimally traumatic surgical techniques. Study Design Retrospective chart review (2002–2010). Setting Tertiary academic referral center. Patients All subjects with significant preoperative low-frequency hearing (≤70 dB HL at 250 Hz) who underwent cochlear implantation with a newer generation implant electrode (Nucleus Contour Advance, Advanced Bionics HR90K [1J and Helix], and Med El Sonata standard H array) were reviewed. Intervention(s) Preimplant and postimplant audiometric thresholds and speech recognition scores were recorded using the electronic medical record. Main Outcome Measure(s) Postimplantation pure tone threshold shifts were used as a surrogate measure for extent of intracochlear injury and correlated with postoperative speech perception scores. Results Between 2002 and 2010, 703 cochlear implant (CI) operations were performed. Data from 126 implants were included in the analysis. The mean preoperative low-frequency pure-tone average was 55.4 dB HL. Hearing preservation was observed in 55% of patients. Patients with hearing preservation were found to have significantly higher postoperative speech perception performance in the cochlear implantation-only condition than those who lost all residual hearing. Conclusion Conservation of acoustic hearing after conventional length cochlear implantation is unpredictable but remains a realistic goal. The combination of improved technology and refined surgical technique may allow for conservation of some residual hearing in more than 50% of patients. Germane to the conventional length CI recipient with substantial hearing loss, minimizing trauma allows for improved speech perception in the electric condition. These findings support the use of minimally traumatic techniques in all CI recipients, even those destined for electric-only stimulation. PMID:21659922
Audiological outcomes of cochlear implantation in Waardenburg Syndrome

PubMed Central

Magalhães, Ana Tereza de Matos; Samuel, Paola Angélica; Goffi-Gomez, Maria Valeria Schimdt; Tsuji, Robinson Koji; Brito, Rubens; Bento, Ricardo Ferreira

2013-01-01

Summary Introduction: The most relevant clinical symptom in Waardenburg syndrome is profound bilateral sensorioneural hearing loss. Aim: To characterize and describe hearing outcomes after cochlear implantation in patients with Waardenburg syndrome to improve preoperative expectations. Method: This was an observational and retrospective study of a series of cases. Children who were diagnosed with Waardenburg syndrome and who received a multichannel cochlear implant between March 1999 and July 2012 were included in the study. Intraoperative neural response telemetry, hearing evaluation, speech perception, and speech production data before and after surgery were assessed. Results: During this period, 806 patients received a cochlear implant and 10 of these (1.2%) were diagnosed with Waardenburg syndrome. Eight of the children received a Nucleus 24® implant and 1 child and 1 adult received a DigiSonic SP implant. The mean age at implantation was 44 months among the children. The average duration of use of a cochlear implant at the time of the study was 43 months. Intraoperative neural responses were present in all cases. Patients who could use the speech processor effectively had a pure tone average of 31 dB in free-field conditions. In addition, the MUSS and MAIS questionnaires revealed improvements in speech perception and production. Four patients did not have a good outcome, which might have been associated with ineffective use of the speech processor. Conclusion: Despite the heterogeneity of the group, patients with Waardenburg syndrome who received cochlear implants were found to have hearing thresholds that allowed access to speech sounds. However, patients who received early intervention and rehabilitation showed better evolution of auditory perception. PMID:25992025
Therapeutic value of nerve growth factor in promoting neural stem cell survival and differentiation and protecting against neuronal hearing loss.

PubMed

Han, Zhao; Wang, Cong-Pin; Cong, Ning; Gu, Yu-Yan; Ma, Rui; Chi, Fang-Lu

2017-04-01

Nerve growth factor (NGF) is a neurotrophic factor that modulates survival and differentiation of neural stem cells (NSCs). We investigated the function of NGF in promoting growth and neuronal differentiation of NSCs isolated from mouse cochlear tissue, as well as its protective properties against gentamicin (GMC) ototoxicity. NSCs were isolated from the cochlea of mice and cultured in vitro. Effect of NGF on survival, neurosphere formation, and differentiation of the NSCs, as well as neurite outgrowth and neural excitability in the subsequent in vitro neuronal network, was examined. Mechanotransduction capacity of intact cochlea and auditory brainstem response (ABR) threshold in mice were also measured following GMC treatment to evaluate protection using NGF against GMC-induced neuronal hearing loss. NGF improved survival, neurosphere formation, and neuronal differentiation of mouse cochlear NSCs in vitro, as well as promoted neurite outgrowth and neural excitability in the NSC-differentiated neuronal culture. In addition, NGF protected mechanotransduction capacity and restored ABR threshold in gentamicin ototoxicity mouse model. Our study supports a potential therapeutic value of NGF in promoting proliferation and differentiation of NSCs into functional neurons in vitro, supporting its protective role in the treatment of neuronal hearing loss.
GATA3 controls the specification of prosensory domain and neuronal survival in the mouse cochlea

PubMed Central

Luo, Xiong-jian; Deng, Min; Xie, Xiaoling; Huang, Liang; Wang, Hui; Jiang, Lichun; Liang, Guoqing; Hu, Fang; Tieu, Roger; Chen, Rui; Gan, Lin

2013-01-01

HDR syndrome (also known as Barakat syndrome) is a developmental disorder characterized by hypoparathyroidism, sensorineural deafness and renal disease. Although genetic mapping and subsequent functional studies indicate that GATA3 haplo-insufficiency causes human HDR syndrome, the role of Gata3 in sensorineural deafness and auditory system development is largely unknown. In this study, we show that Gata3 is continuously expressed in the developing mouse inner ear. Conditional knockout of Gata3 in the developing inner ear disrupts the morphogenesis of mouse inner ear, resulting in a disorganized and shortened cochlear duct with significant fewer hair cells and supporting cells. Loss of Gata3 function leads to the failure in the specification of prosensory domain and subsequently, to increased cell death in the cochlear duct. Moreover, though the initial generation of cochleovestibular ganglion (CVG) cells is not affected in Gata3-null mice, spiral ganglion neurons (SGNs) are nearly depleted due to apoptosis. Our results demonstrate the essential role of Gata3 in specifying the prosensory domain in the cochlea and in regulating the survival of SGNs, thus identifying a molecular mechanism underlying human HDR syndrome. PMID:23666531
Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells.

PubMed

McLean, Will J; Yin, Xiaolei; Lu, Lin; Lenz, Danielle R; McLean, Dalton; Langer, Robert; Karp, Jeffrey M; Edge, Albert S B

2017-02-21

Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor. The Lgr5-expressing cells differentiate into hair cells in high yield. From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Auditory Performance and Electrical Stimulation Measures in Cochlear Implant Recipients With Auditory Neuropathy Compared With Severe to Profound Sensorineural Hearing Loss.

PubMed

Attias, Joseph; Greenstein, Tally; Peled, Miriam; Ulanovski, David; Wohlgelernter, Jay; Raveh, Eyal

The aim of the study was to compare auditory and speech outcomes and electrical parameters on average 8 years after cochlear implantation between children with isolated auditory neuropathy (AN) and children with sensorineural hearing loss (SNHL). The study was conducted at a tertiary, university-affiliated pediatric medical center. The cohort included 16 patients with isolated AN with current age of 5 to 12.2 years who had been using a cochlear implant for at least 3.4 years and 16 control patients with SNHL matched for duration of deafness, age at implantation, type of implant, and unilateral/bilateral implant placement. All participants had had extensive auditory rehabilitation before and after implantation, including the use of conventional hearing aids. Most patients received Cochlear Nucleus devices, and the remainder either Med-El or Advanced Bionics devices. Unaided pure-tone audiograms were evaluated before and after implantation. Implantation outcomes were assessed by auditory and speech recognition tests in quiet and in noise. Data were also collected on the educational setting at 1 year after implantation and at school age. The electrical stimulation measures were evaluated only in the Cochlear Nucleus implant recipients in the two groups. Similar mapping and electrical measurement techniques were used in the two groups. Electrical thresholds, comfortable level, dynamic range, and objective neural response telemetry threshold were measured across the 22-electrode array in each patient. Main outcome measures were between-group differences in the following parameters: (1) Auditory and speech tests. (2) Residual hearing. (3) Electrical stimulation parameters. (4) Correlations of residual hearing at low frequencies with electrical thresholds at the basal, middle, and apical electrodes. The children with isolated AN performed equally well to the children with SNHL on auditory and speech recognition tests in both quiet and noise. More children in the AN group than the SNHL group were attending mainstream educational settings at school age, but the difference was not statistically significant. Significant between-group differences were noted in electrical measurements: the AN group was characterized by a lower current charge to reach subjective electrical thresholds, lower comfortable level and dynamic range, and lower telemetric neural response threshold. Based on pure-tone audiograms, the children with AN also had more residual hearing before and after implantation. Highly positive coefficients were found on correlation analysis between T levels across the basal and midcochlear electrodes and low-frequency acoustic thresholds. Prelingual children with isolated AN who fail to show expected oral and auditory progress after extensive rehabilitation with conventional hearing aids should be considered for cochlear implantation. Children with isolated AN had similar pattern as children with SNHL on auditory performance tests after cochlear implantation. The lower current charge required to evoke subjective and objective electrical thresholds in children with AN compared with children with SNHL may be attributed to the contribution to electrophonic hearing from the remaining neurons and hair cells. In addition, it is also possible that mechanical stimulation of the basilar membrane, as in acoustic stimulation, is added to the electrical stimulation of the cochlear implant.

Deletion of Fmr1 Alters Function and Synaptic Inputs in the Auditory Brainstem

PubMed Central

Rotschafer, Sarah E.; Marshak, Sonya; Cramer, Karina S.

2015-01-01

Fragile X Syndrome (FXS), a neurodevelopmental disorder, is the most prevalent single-gene cause of autism spectrum disorder. Autism has been associated with impaired auditory processing, abnormalities in the auditory brainstem response (ABR), and reduced cell number and size in the auditory brainstem nuclei. FXS is characterized by elevated cortical responses to sound stimuli, with some evidence for aberrant ABRs. Here, we assessed ABRs and auditory brainstem anatomy in Fmr1 -/- mice, an animal model of FXS. We found that Fmr1 -/- mice showed elevated response thresholds to both click and tone stimuli. Amplitudes of ABR responses were reduced in Fmr1 -/- mice for early peaks of the ABR. The growth of the peak I response with sound intensity was less steep in mutants that in wild type mice. In contrast, amplitudes and response growth in peaks IV and V did not differ between these groups. We did not observe differences in peak latencies or in interpeak latencies. Cell size was reduced in Fmr1 -/- mice in the ventral cochlear nucleus (VCN) and in the medial nucleus of the trapezoid body (MNTB). We quantified levels of inhibitory and excitatory synaptic inputs in these nuclei using markers for presynaptic proteins. We measured VGAT and VGLUT immunolabeling in VCN, MNTB, and the lateral superior olive (LSO). VGAT expression in MNTB was significantly greater in the Fmr1 -/- mouse than in wild type mice. Together, these observations demonstrate that FXS affects peripheral and central aspects of hearing and alters the balance of excitation and inhibition in the auditory brainstem. PMID:25679778
Proteomics, bioinformatics and targeted gene expression analysis reveals up-regulation of cochlin and identifies other potential biomarkers in the mouse model for deafness in usher syndrome type 1F

PubMed Central

Chance, Mark R.; Chang, Jinsook; Liu, Shuqing; Gokulrangan, Giridharan; Chen, Daniel H.-C.; Lindsay, Aaron; Geng, Ruishuang; Zheng, Qing Y.; Alagramam, Kumar

2010-01-01

Proteins and protein networks associated with cochlear pathogenesis in the Ames waltzer (av) mouse, a model for deafness in Usher syndrome 1F (USH1F), were identified. Cochlear protein from wild-type and av mice at postnatal day 30, a time point in which cochlear pathology is well established, was analyzed by quantitative 2D gel electrophoresis followed by mass spectrometry (MS). The analytic gel resolved 2270 spots; 69 spots showed significant changes in intensity in the av cochlea compared with the control. The cochlin protein was identified in 20 peptide spots, most of which were up-regulated, while a few were down-regulated. Analysis of MS sequence data showed that, in the av cochlea, a set of full-length isoforms of cochlin was up-regulated, while isoforms missing the N-terminal FCH/LCCL domain were down-regulated. Protein interaction network analysis of all differentially expressed proteins was performed with Metacore software. That analysis revealed a number of statistically significant candidate protein networks predicted to be altered in the affected cochlea. Quantitative PCR (qPCR) analysis of select candidates from the proteomic and bioinformatic investigations showed up-regulation of Coch mRNA and those of p53, Brn3a and Nrf2, transcription factors linked to stress response and survival. Increased mRNA of Brn3a and Nrf2 has previously been associated with increased expression of cochlin in human glaucomatous trabecular meshwork. Our report strongly suggests that increased level of cochlin is an important etiologic factor leading to the degeneration of cochlear neuroepithelia in the USH1F model. PMID:20097680
Hepatocyte Growth Factor-c-MET Signaling Mediates the Development of Nonsensory Structures of the Mammalian Cochlea and Hearing.

PubMed

Shibata, Shumei; Miwa, Toru; Wu, Hsiao-Huei; Levitt, Pat; Ohyama, Takahiro

2016-08-03

The stria vascularis is a nonsensory structure that is essential for auditory hair cell function by maintaining potassium concentration of the scala media. During mouse embryonic development, a subpopulation of neural crest cell-derived melanocytes migrates and incorporates into a subregion of the cochlear epithelium, forming the intermediate cell layer of the stria vascularis. The relation of this developmental process to stria vascularis function is currently unknown. In characterizing the molecular differentiation of developing peripheral auditory structures, we discovered that hepatocyte growth factor (Hgf) is expressed in the future stria vascularis of the cochlear epithelium. Its receptor tyrosine kinase, c-Met, is expressed in the cochlear epithelium and melanocyte-derived intermediate cells in the stria vascularis. Genetic dissection of HGF signaling via c-MET reveals that the incorporation of the melanocytes into the future stria vascularis of the cochlear duct requires c-MET signaling. In addition, inactivation of either the ligand or receptor developmentally resulted in a profound hearing loss at young adult stages. These results suggest a novel connection between HGF signaling and deafness via melanocyte deficiencies. We found the roles of hepatocyte growth factor (HGF) signaling in stria vascularis development for the first time and that lack of HGF signaling in the inner ear leads to profound hearing loss in the mouse. Our findings reveal a novel mechanism that may underlie human deafness DFNB39 and DFNB97. Our findings reveal an additional example of context-dependent c-MET signaling diversity, required here for proper cellular invasion developmentally that is essential for specific aspects of auditory-related organogenesis. Copyright © 2016 the authors 0270-6474/16/368200-10$15.00/0.
Hepatocyte Growth Factor–c-MET Signaling Mediates the Development of Nonsensory Structures of the Mammalian Cochlea and Hearing

PubMed Central

Shibata, Shumei; Miwa, Toru; Wu, Hsiao-Huei; Levitt, Pat

2016-01-01

The stria vascularis is a nonsensory structure that is essential for auditory hair cell function by maintaining potassium concentration of the scala media. During mouse embryonic development, a subpopulation of neural crest cell-derived melanocytes migrates and incorporates into a subregion of the cochlear epithelium, forming the intermediate cell layer of the stria vascularis. The relation of this developmental process to stria vascularis function is currently unknown. In characterizing the molecular differentiation of developing peripheral auditory structures, we discovered that hepatocyte growth factor (Hgf) is expressed in the future stria vascularis of the cochlear epithelium. Its receptor tyrosine kinase, c-Met, is expressed in the cochlear epithelium and melanocyte-derived intermediate cells in the stria vascularis. Genetic dissection of HGF signaling via c-MET reveals that the incorporation of the melanocytes into the future stria vascularis of the cochlear duct requires c-MET signaling. In addition, inactivation of either the ligand or receptor developmentally resulted in a profound hearing loss at young adult stages. These results suggest a novel connection between HGF signaling and deafness via melanocyte deficiencies. SIGNIFICANCE STATEMENT We found the roles of hepatocyte growth factor (HGF) signaling in stria vascularis development for the first time and that lack of HGF signaling in the inner ear leads to profound hearing loss in the mouse. Our findings reveal a novel mechanism that may underlie human deafness DFNB39 and DFNB97. Our findings reveal an additional example of context-dependent c-MET signaling diversity, required here for proper cellular invasion developmentally that is essential for specific aspects of auditory-related organogenesis. PMID:27488639
Chronic tinnitus and unipolar brush cell alterations in the cerebellum and dorsal cochlear nucleus.

PubMed

Brozoski, Thomas; Brozoski, Daniel; Wisner, Kurt; Bauer, Carol

2017-07-01

Animal model research has shown that the central features of tinnitus, the perception of sound without an acoustic correlate, include elevated spontaneous and stimulus-driven activity, enhanced burst-mode firing, decreased variance of inter-spike intervals, and distortion of tonotopic frequency representation. Less well documented are cell-specific correlates of tinnitus. Unipolar brush cell (UBC) alterations in animals with psychophysical evidence of tinnitus has recently been reported. UBCs are glutamatergic interneurons that appear to function as local-circuit signal amplifiers. UBCs are abundant in the dorsal cochlear nucleus (DCN) and very abundant in the flocculus (FL) and paraflocculus (PFL) of the cerebellum. In the present research, two indicators of UBC structure and function were examined: Doublecortin (DCX) and epidermal growth factor receptor substrate 8 (Eps8). DCX is a protein that binds to microtubules where it can modify their assembly and growth. Eps8 is a cell-surface tyrosine kinase receptor mediating the response to epidermal growth factor; it appears to have a role in actin polymerization as well as cytoskeletal protein interactions. Both functions could contribute to synaptic remodeling. In the present research UBC Eps8 and DCX immunoreactivity (IR) were determined in 4 groups of rats distinguished by their exposure to high-level sound and psychophysical performance: Unexposed, exposed to high-level sound with behavioral evidence of tinnitus, and two exposed groups without behavioral evidence of tinnitus. Compared to unexposed controls, exposed animals with tinnitus had Eps8 IR elevated in their PFL; other structures were not affected, nor was DCX IR affected. This was interpreted as UBC upregulation in animals with tinnitus. Exposure that failed to produce tinnitus did not increase either Eps8 or DCX IR. Rather Eps8 IR was decreased in the FL and DCN of one subgroup (Least-Tinnitus), while DCX IR decreased in the FL of the other subgroup (No-Tinnitus). Neuron degeneration was also documented in the cochlear nucleus and PFL of exposed animals, both with and without tinnitus. Degeneration was not found in unexposed animals. Implications for tinnitus neuropathy are discussed in the context of synaptic remodeling and cerebellar sensory modulation. Copyright © 2017 Elsevier B.V. All rights reserved.
Neurometric amplitude-modulation detection threshold in the guinea-pig ventral cochlear nucleus

PubMed Central

Sayles, Mark; Füllgrabe, Christian; Winter, Ian M

2013-01-01

Amplitude modulation (AM) is a pervasive feature of natural sounds. Neural detection and processing of modulation cues is behaviourally important across species. Although most ecologically relevant sounds are not fully modulated, physiological studies have usually concentrated on fully modulated (100% modulation depth) signals. Psychoacoustic experiments mainly operate at low modulation depths, around detection threshold (∼5% AM). We presented sinusoidal amplitude-modulated tones, systematically varying modulation depth between zero and 100%, at a range of modulation frequencies, to anaesthetised guinea-pigs while recording spikes from neurons in the ventral cochlear nucleus (VCN). The cochlear nucleus is the site of the first synapse in the central auditory system. At this locus significant signal processing occurs with respect to representation of AM signals. Spike trains were analysed in terms of the vector strength of spike synchrony to the amplitude envelope. Neurons showed either low-pass or band-pass temporal modulation transfer functions, with the proportion of band-pass responses increasing with increasing sound level. The proportion of units showing a band-pass response varies with unit type: sustained chopper (CS) > transient chopper (CT) > primary-like (PL). Spike synchrony increased with increasing modulation depth. At the lowest modulation depth (6%), significant spike synchrony was only observed near to the unit's best modulation frequency for all unit types tested. Modulation tuning therefore became sharper with decreasing modulation depth. AM detection threshold was calculated for each individual unit as a function of modulation frequency. Chopper units have significantly better AM detection thresholds than do primary-like units. AM detection threshold is significantly worse at 40 dB vs. 10 dB above pure-tone spike rate threshold. Mean modulation detection thresholds for sounds 10 dB above pure-tone spike rate threshold at best modulation frequency are (95% CI) 11.6% (10.0–13.1) for PL units, 9.8% (8.2–11.5) for CT units, and 10.8% (8.4–13.2) for CS units. The most sensitive guinea-pig VCN single unit AM detection thresholds are similar to human psychophysical performance (∼3% AM), while the mean neurometric thresholds approach whole animal behavioural performance (∼10% AM). PMID:23629508
Verification of a Proposed Clinical Electroacoustic Test Protocol for Personal Digital Modulation Receivers Coupled to Cochlear Implant Sound Processors.

PubMed

Nair, Erika L; Sousa, Rhonda; Wannagot, Shannon

Guidelines established by the AAA currently recommend behavioral testing when fitting frequency modulated (FM) systems to individuals with cochlear implants (CIs). A protocol for completing electroacoustic measures has not yet been validated for personal FM systems or digital modulation (DM) systems coupled to CI sound processors. In response, some professionals have used or altered the AAA electroacoustic verification steps for fitting FM systems to hearing aids when fitting FM systems to CI sound processors. More recently steps were outlined in a proposed protocol. The purpose of this research is to review and compare the electroacoustic test measures outlined in a 2013 article by Schafer and colleagues in the Journal of the American Academy of Audiology titled "A Proposed Electroacoustic Test Protocol for Personal FM Receivers Coupled to Cochlear Implant Sound Processors" to the AAA electroacoustic verification steps for fitting FM systems to hearing aids when fitting DM systems to CI users. Electroacoustic measures were conducted on 71 CI sound processors and Phonak Roger DM systems using a proposed protocol and an adapted AAA protocol. Phonak's recommended default receiver gain setting was used for each CI sound processor manufacturer and adjusted if necessary to achieve transparency. Electroacoustic measures were conducted on Cochlear and Advanced Bionics (AB) sound processors. In this study, 28 Cochlear Nucleus 5/CP810 sound processors, 26 Cochlear Nucleus 6/CP910 sound processors, and 17 AB Naida CI Q70 sound processors were coupled in various combinations to Phonak Roger DM dedicated receivers (25 Phonak Roger 14 receivers-Cochlear dedicated receiver-and 9 Phonak Roger 17 receivers-AB dedicated receiver) and 20 Phonak Roger Inspiro transmitters. Employing both the AAA and the Schafer et al protocols, electroacoustic measurements were conducted with the Audioscan Verifit in a clinical setting on 71 CI sound processors and Phonak Roger DM systems to determine transparency and verify FM advantage, comparing speech inputs (65 dB SPL) in an effort to achieve equal outputs. If transparency was not achieved at Phonak's recommended default receiver gain, adjustments were made to the receiver gain. The integrity of the signal was monitored with the appropriate manufacturer's monitor earphones. Using the AAA hearing aid protocol, 50 of the 71 CI sound processors achieved transparency, and 59 of the 71 CI sound processors achieved transparency when using the proposed protocol at Phonak's recommended default receiver gain. After the receiver gain was adjusted, 3 of 21 CI sound processors still did not meet transparency using the AAA protocol, and 2 of 12 CI sound processors still did not meet transparency using the Schafer et al proposed protocol. Both protocols were shown to be effective in taking reliable electroacoustic measurements and demonstrate transparency. Both protocols are felt to be clinically feasible and to address the needs of populations that are unable to reliably report regarding the integrity of their personal DM systems. American Academy of Audiology
Intrinsic regenerative potential of murine cochlear supporting cells.

PubMed

Sinkkonen, Saku T; Chai, Renjie; Jan, Taha A; Hartman, Byron H; Laske, Roman D; Gahlen, Felix; Sinkkonen, Wera; Cheng, Alan G; Oshima, Kazuo; Heller, Stefan

2011-01-01

The lack of cochlear regenerative potential is the main cause for the permanence of hearing loss. Albeit quiescent in vivo, dissociated non-sensory cells from the neonatal cochlea proliferate and show ability to generate hair cell-like cells in vitro. Only a few non-sensory cell-derived colonies, however, give rise to hair cell-like cells, suggesting that sensory progenitor cells are a subpopulation of proliferating non-sensory cells. Here we purify from the neonatal mouse cochlea four different non-sensory cell populations by fluorescence-activated cell sorting (FACS). All four populations displayed proliferative potential, but only lesser epithelial ridge and supporting cells robustly gave rise to hair cell marker-positive cells. These results suggest that cochlear supporting cells and cells of the lesser epithelial ridge show robust potential to de-differentiate into prosensory cells that proliferate and undergo differentiation in similar fashion to native prosensory cells of the developing inner ear.
A clinical assessment of cochlear implant recipient performance: implications for individualized map settings in specific environments.

PubMed

Hey, Matthias; Hocke, Thomas; Mauger, Stefan; Müller-Deile, Joachim

2016-11-01

Individual speech intelligibility was measured in quiet and noise for cochlear Implant recipients upgrading from the Freedom to the CP900 series sound processor. The postlingually deafened participants (n = 23) used either Nucleus CI24RE or CI512 cochlear implant, and currently wore a Freedom sound processor. A significant group mean improvement in speech intelligibility was found in quiet (Freiburg monosyllabic words at 50 dB SPL ) and in noise (adaptive Oldenburger sentences in noise) for the two CP900 series SmartSound programs compared to the Freedom program. Further analysis was carried out on individual's speech intelligibility outcomes in quiet and in noise. Results showed a significant improvement or decrement for some recipients when upgrading to the new programs. To further increase speech intelligibility outcomes when upgrading, an enhanced upgrade procedure is proposed that includes additional testing with different signal-processing schemes. Implications of this research are that future automated scene analysis and switching technologies could provide additional performance improvements by introducing individualized scene-dependent settings.
Focused tight dressing does not prevent cochlear implant magnet migration under 1.5 Tesla MRI.

PubMed

Cuda, D; Murri, A; Succo, G

2013-04-01

We report a retrospective case of inner magnet migration, which occurred after 1.5 Tesla MRI scanning in an adult recipient of a bilateral cochlear implant (CI) despite a focused head dressing. The patient, bilaterally implanted with Nucleus 5 CIs (Cochlear LTD, Sydney, Australia), underwent a 1.5 Tesla cholangio-MRI scan for biliary duct pathology. In subsequent days, a focal skin alteration appeared over the left inner coil. Plain skull radiographs showed partial magnet migration on the left side. Surgical exploration confirmed magnet twisting; the magnet was effectively repositioned. Left CI performance was restored to pre-migration level. The wound healed without complications. Thus, focused dressing does not prevent magnet migration in CI recipients undergoing 1.5 Tesla MRI. All patients should be counselled on this potential complication. A minor surgical procedure is required to reposition the magnet. Nevertheless, timely diagnosis is necessary to prevent skin breakdown and subsequent device contamination. Plain skull radiograph is very effective in identifying magnet twisting; it should be performed systematically after MRI or minimally on all suspected cases.
Age-related cochlear cytokine gene expression in the BALB/cJ mouse with systemic versus intratympanic dosing of steroid drugs.

PubMed

Tokarz, Sara A; Pang, Jiaqing; Grosz, Anna; Kempton, J Beth; Trune, Dennis R; Pillers, De-Ann M

2013-07-01

Age-related differences in the expression of inflammatory cytokines in the inner ear may contribute to the development of age-related hearing loss (ARHL). ARHL is characterized by tissue remodeling, ischemia, ion homeostasis, and inflammation. Steroid therapy is an otoprotective strategy that likely acts by reducing inflammation. We examined age-related changes in cytokine gene expression in the cochlea of the BALB/cJ mouse model of premature ARHL after systemic or intratympanic steroid delivery. 'Young' (2.5-3 months) and 'Old' (5-9 months) mice were treated with dexamethasone or fludrocortisone administered either orally or intratympanically. Cytokine gene expression in cochlear RNA was analyzed using prefabricated cDNA arrays. Old groups were compared to Young groups to identify age-related changes. Down-regulation of a cytokine associated with bone remodeling (SPP1) was observed in the untreated Old group. Numerous genes were up- or down-regulated by more than twofold by steroid treatment, including proinflammatory interleukins (IL-16) and anti-inflammatory cytokines.
Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome

PubMed Central

Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

2015-01-01

Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1−/− mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0–P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner’s membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1−/− mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. PMID:26084842
Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.

PubMed

Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

2015-08-01

Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
Lack of Intrinsic GABAergic Connections in the Thalamic Reticular Nucleus of the Mouse.

PubMed

Hou, Guoqiang; Smith, Alison G; Zhang, Zhong-Wei

2016-07-06

It is generally thought that neurons in the thalamic reticular nucleus (TRN) form GABAergic synapses with other TRN neurons and that these interconnections are important for the function of the TRN. However, the existence of such intrinsic connections is controversial. We combine two complementary approaches to examine intrinsic GABAergic connections in the TRN of the mouse. We find that optogenetic stimulation of TRN neurons and their axons evokes GABAergic IPSCs in TRN neurons in mice younger than 2 weeks of age but fails to do so after that age. Blocking synaptic release from TRN neurons through conditional deletion of vesicular GABA transporter has no effect on spontaneous IPSCs recorded in TRN neurons aged 2 weeks or older while dramatically reducing GABAergic transmission in thalamic relay neurons. These results demonstrate that except for a short period after birth, the TRN of the mouse lacks intrinsic GABAergic connections. The thalamic reticular nucleus has a critical role in modulating information transfer from the thalamus to the cortex. It has been proposed that neurons in the thalamic reticular nucleus are interconnected through GABAergic synapses and that these connections serve important functions. Our results show that except for the first 2 weeks after birth, the thalamic reticular nucleus of the mouse lacks intrinsic GABAergic connections. Copyright © 2016 the authors 0270-6474/16/367246-07$15.00/0.
Recognition and localization of speech by adult cochlear implant recipients wearing a digital hearing aid in the nonimplanted ear (bimodal hearing).

PubMed

Potts, Lisa G; Skinner, Margaret W; Litovsky, Ruth A; Strube, Michael J; Kuk, Francis

2009-06-01

The use of bilateral amplification is now common clinical practice for hearing aid users but not for cochlear implant recipients. In the past, most cochlear implant recipients were implanted in one ear and wore only a monaural cochlear implant processor. There has been recent interest in benefits arising from bilateral stimulation that may be present for cochlear implant recipients. One option for bilateral stimulation is the use of a cochlear implant in one ear and a hearing aid in the opposite nonimplanted ear (bimodal hearing). This study evaluated the effect of wearing a cochlear implant in one ear and a digital hearing aid in the opposite ear on speech recognition and localization. A repeated-measures correlational study was completed. Nineteen adult Cochlear Nucleus 24 implant recipients participated in the study. The participants were fit with a Widex Senso Vita 38 hearing aid to achieve maximum audibility and comfort within their dynamic range. Soundfield thresholds, loudness growth, speech recognition, localization, and subjective questionnaires were obtained six-eight weeks after the hearing aid fitting. Testing was completed in three conditions: hearing aid only, cochlear implant only, and cochlear implant and hearing aid (bimodal). All tests were repeated four weeks after the first test session. Repeated-measures analysis of variance was used to analyze the data. Significant effects were further examined using pairwise comparison of means or in the case of continuous moderators, regression analyses. The speech-recognition and localization tasks were unique, in that a speech stimulus presented from a variety of roaming azimuths (140 degree loudspeaker array) was used. Performance in the bimodal condition was significantly better for speech recognition and localization compared to the cochlear implant-only and hearing aid-only conditions. Performance was also different between these conditions when the location (i.e., side of the loudspeaker array that presented the word) was analyzed. In the bimodal condition, the speech-recognition and localization tasks were equal regardless of which side of the loudspeaker array presented the word, while performance was significantly poorer for the monaural conditions (hearing aid only and cochlear implant only) when the words were presented on the side with no stimulation. Binaural loudness summation of 1-3 dB was seen in soundfield thresholds and loudness growth in the bimodal condition. Measures of the audibility of sound with the hearing aid, including unaided thresholds, soundfield thresholds, and the Speech Intelligibility Index, were significant moderators of speech recognition and localization. Based on the questionnaire responses, participants showed a strong preference for bimodal stimulation. These findings suggest that a well-fit digital hearing aid worn in conjunction with a cochlear implant is beneficial to speech recognition and localization. The dynamic test procedures used in this study illustrate the importance of bilateral hearing for locating, identifying, and switching attention between multiple speakers. It is recommended that unilateral cochlear implant recipients, with measurable unaided hearing thresholds, be fit with a hearing aid.
Distinct Neural Properties in the Low-Frequency Region of the Chicken Cochlear Nucleus Magnocellularis

PubMed Central

2017-01-01

Abstract Topography in the avian cochlear nucleus magnocellularis (NM) is represented as gradually increasing characteristic frequency (CF) along the caudolateral-to-rostromedial axis. In this study, we characterized the organization and cell biophysics of the caudolateral NM (NMc) in chickens (Gallus gallus). Examination of cellular and dendritic architecture first revealed that NMc contains small neurons and extensive dendritic processes, in contrast to adendritic, large neurons located more rostromedially. Individual dye-filling study further demonstrated that NMc is divided into two subregions, with NMc2 neurons having larger and more complex dendritic fields than NMc1. Axonal tract tracing studies confirmed that NMc1 and NMc2 neurons receive afferent inputs from the auditory nerve and the superior olivary nucleus, similar to the adendritic NM. However, the auditory axons synapse with NMc neurons via small bouton-like terminals, unlike the large end bulb synapses on adendritic NM neurons. Immunocytochemistry demonstrated that most NMc2 neurons express cholecystokinin but not calretinin, distinct from NMc1 and adendritic NM neurons that are cholecystokinin negative and mostly calretinin positive. Finally, whole-cell current clamp recordings revealed that NMc neurons require significantly lower threshold current for action potential generation than adendritic NM neurons. Moreover, in contrast to adendritic NM neurons that generate a single-onset action potential, NMc neurons generate multiple action potentials to suprathreshold sustained depolarization. Taken together, our data indicate that NMc contains multiple neuron types that are structurally, connectively, molecularly, and physiologically different from traditionally defined NM neurons, emphasizing specialized neural properties for processing low-frequency sounds. PMID:28413822
Interaural Phase and Level Difference Sensitivity in Low-Frequency Neurons in the Lateral Superior Olive

PubMed Central

Tollin, Daniel J.; Yin, Tom C. T.

2006-01-01

The lateral superior olive (LSO) is believed to encode differences in sound level at the two ears, a cue for azimuthal sound location. Most high-frequency-sensitive LSO neurons are binaural, receiving inputs from both ears. An inhibitory input from the contralateral ear, via the medial nucleus of the trapezoid body (MNTB), and excitatory input from the ipsilateral ear enable level differences to be encoded. However, the classical descriptions of low-frequency-sensitive neurons report primarily monaural cells with no contralateral inhibition. Anatomical and physiological evidence, however, shows that low-frequency LSO neurons receive low-frequency inhibitory input from ipsilateral MNTB, which in turn receives excitatory input from the contralateral cochlear nucleus and low-frequency excitatory input from the ipsilateral cochlear nucleus. Therefore, these neurons would be expected to be binaural with contralateral inhibition. Here, we re-examined binaural interaction in low-frequency (less than ~3 kHz) LSO neurons and phase locking in the MNTB. Phase locking to low-frequency tones in MNTB and ipsilaterally driven LSO neurons with frequency sensitivities < 1.2 kHz was enhanced relative to the auditory nerve. Moreover, most low-frequency LSO neurons exhibited contralateral inhibition: ipsilaterally driven responses were suppressed by raising the level of the contralateral stimulus; most neurons were sensitive to interaural time delays in pure tone and noise stimuli such that inhibition was nearly maximal when the stimuli were presented to the ears in-phase. The data demonstrate that low-frequency LSO neurons of cat are not monaural and can exhibit contralateral inhibition like their high-frequency counterparts. PMID:16291937
Intraoperative Cochlear Implant Device Testing Utilizing an Automated Remote System: A Prospective Pilot Study.

PubMed

Lohmann, Amanda R; Carlson, Matthew L; Sladen, Douglas P

2018-03-01

Intraoperative cochlear implant device testing provides valuable information regarding device integrity, electrode position, and may assist with determining initial stimulation settings. Manual intraoperative device testing during cochlear implantation requires the time and expertise of a trained audiologist. The purpose of the current study is to investigate the feasibility of using automated remote intraoperative cochlear implant reverse telemetry testing as an alternative to standard testing. Prospective pilot study evaluating intraoperative remote automated impedance and Automatic Neural Response Telemetry (AutoNRT) testing in 34 consecutive cochlear implant surgeries using the Intraoperative Remote Assistant (Cochlear Nucleus CR120). In all cases, remote intraoperative device testing was performed by trained operating room staff. A comparison was made to the "gold standard" of manual testing by an experienced cochlear implant audiologist. Electrode position and absence of tip fold-over was confirmed using plain film x-ray. Automated remote reverse telemetry testing was successfully completed in all patients. Intraoperative x-ray demonstrated normal electrode position without tip fold-over. Average impedance values were significantly higher using standard testing versus CR120 remote testing (standard mean 10.7 kΩ, SD 1.2 vs. CR120 mean 7.5 kΩ, SD 0.7, p < 0.001). There was strong agreement between standard manual testing and remote automated testing with regard to the presence of open or short circuits along the array. There were, however, two cases in which standard testing identified an open circuit, when CR120 testing showed the circuit to be closed. Neural responses were successfully obtained in all patients using both systems. There was no difference in basal electrode responses (standard mean 195.0 μV, SD 14.10 vs. CR120 194.5 μV, SD 14.23; p = 0.7814); however, more favorable (lower μV amplitude) results were obtained with the remote automated system in the apical 10 electrodes (standard 185.4 μV, SD 11.69 vs. CR120 177.0 μV, SD 11.57; p value < 0.001). These preliminary data demonstrate that intraoperative cochlear implant device testing using a remote automated system is feasible. This system may be useful for cochlear implant programs with limited audiology support or for programs looking to streamline intraoperative device testing protocols. Future studies with larger patient enrollment are required to validate these promising, but preliminary, findings.
Functional modeling of the human auditory brainstem response to broadband stimulationa)

PubMed Central

Verhulst, Sarah; Bharadwaj, Hari M.; Mehraei, Golbarg; Shera, Christopher A.; Shinn-Cunningham, Barbara G.

2015-01-01

Population responses such as the auditory brainstem response (ABR) are commonly used for hearing screening, but the relationship between single-unit physiology and scalp-recorded population responses are not well understood. Computational models that integrate physiologically realistic models of single-unit auditory-nerve (AN), cochlear nucleus (CN) and inferior colliculus (IC) cells with models of broadband peripheral excitation can be used to simulate ABRs and thereby link detailed knowledge of animal physiology to human applications. Existing functional ABR models fail to capture the empirically observed 1.2–2 ms ABR wave-V latency-vs-intensity decrease that is thought to arise from level-dependent changes in cochlear excitation and firing synchrony across different tonotopic sections. This paper proposes an approach where level-dependent cochlear excitation patterns, which reflect human cochlear filter tuning parameters, drive AN fibers to yield realistic level-dependent properties of the ABR wave-V. The number of free model parameters is minimal, producing a model in which various sources of hearing-impairment can easily be simulated on an individualized and frequency-dependent basis. The model fits latency-vs-intensity functions observed in human ABRs and otoacoustic emissions while maintaining rate-level and threshold characteristics of single-unit AN fibers. The simulations help to reveal which tonotopic regions dominate ABR waveform peaks at different stimulus intensities. PMID:26428802
Spread of cochlear excitation during stimulation with pulsed infrared radiation: inferior colliculus measurements

NASA Astrophysics Data System (ADS)

Richter, C.-P.; Rajguru, S. M.; Matic, A. I.; Moreno, E. L.; Fishman, A. J.; Robinson, A. M.; Suh, E.; Walsh, J. T., Jr.

2011-10-01

Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal-hearing animals. The radiation was delivered via a 200 µm diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves (STCs) were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ~22% had two maxima and ~13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC STCs indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic tone pips.

Prevention and Treatment of Noise-Induced Tinnitus. Revision

DTIC Science & Technology

2013-07-01

CTBP2 immunolabeling) for their loss following noise. Sub-Task 1c: Assessment of Auditory Nerve ( VGLUT1 immunolabel) terminals on neurons in Ventral...and Dorsal Cochlear Nucleus (VCN, DCN) for their loss following noise. Sub-Task 1d: Assessment of VGLUT2 , VAT & VGAT immunolabeled terminals in VCN...significant reduction in connections compared to animals without noise exposure. Sub-Task 1c: Assessment of Auditory Nerve ( VGLUT1 immunolabel
Arctigenin protects against neuronal hearing loss by promoting neural stem cell survival and differentiation.

PubMed

Huang, Xinghua; Chen, Mo; Ding, Yan; Wang, Qin

2017-03-01

Neuronal hearing loss has become a prevalent health problem. This study focused on the function of arctigenin (ARC) in promoting survival and neuronal differentiation of mouse cochlear neural stem cells (NSCs), and its protection against gentamicin (GMC) induced neuronal hearing loss. Mouse cochlea was used to isolate NSCs, which were subsequently cultured in vitro. The effects of ARC on NSC survival, neurosphere formation, differentiation of NSCs, neurite outgrowth, and neural excitability in neuronal network in vitro were examined. Mechanotransduction ability demonstrated by intact cochlea, auditory brainstem response (ABR), and distortion product optoacoustic emissions (DPOAE) amplitude in mice were measured to evaluate effects of ARC on GMC-induced neuronal hearing loss. ARC increased survival, neurosphere formation, neuron differentiation of NSCs in mouse cochlear in vitro. ARC also promoted the outgrowth of neurites, as well as neural excitability of the NSC-differentiated neuron culture. Additionally, ARC rescued mechanotransduction capacity, restored the threshold shifts of ABR and DPOAE in our GMC ototoxicity murine model. This study supports the potential therapeutic role of ARC in promoting both NSCs proliferation and differentiation in vitro to functional neurons, thus supporting its protective function in the therapeutic treatment of neuropathic hearing loss in vivo. © 2017 Wiley Periodicals, Inc.
Vibration of the organ of Corti within the cochlear apex in mice

PubMed Central

Gao, Simon S.; Wang, Rosalie; Raphael, Patrick D.; Moayedi, Yalda; Groves, Andrew K.; Zuo, Jian; Applegate, Brian E.

2014-01-01

The tonotopic map of the mammalian cochlea is commonly thought to be determined by the passive mechanical properties of the basilar membrane. The other tissues and cells that make up the organ of Corti also have passive mechanical properties; however, their roles are less well understood. In addition, active forces produced by outer hair cells (OHCs) enhance the vibration of the basilar membrane, termed cochlear amplification. Here, we studied how these biomechanical components interact using optical coherence tomography, which permits vibratory measurements within tissue. We measured not only classical basilar membrane tuning curves, but also vibratory responses from the rest of the organ of Corti within the mouse cochlear apex in vivo. As expected, basilar membrane tuning was sharp in live mice and broad in dead mice. Interestingly, the vibratory response of the region lateral to the OHCs, the “lateral compartment,” demonstrated frequency-dependent phase differences relative to the basilar membrane. This was sharply tuned in both live and dead mice. We then measured basilar membrane and lateral compartment vibration in transgenic mice with targeted alterations in cochlear mechanics. Prestin499/499, Prestin−/−, and TectaC1509G/C1509G mice demonstrated no cochlear amplification but maintained the lateral compartment phase difference. In contrast, SfswapTg/Tg mice maintained cochlear amplification but did not demonstrate the lateral compartment phase difference. These data indicate that the organ of Corti has complex micromechanical vibratory characteristics, with passive, yet sharply tuned, vibratory characteristics associated with the supporting cells. These characteristics may tune OHC force generation to produce the sharp frequency selectivity of mammalian hearing. PMID:24920025
Bilateral Changes of Spontaneous Activity Within the Central Auditory Pathway Upon Chronic Unilateral Intracochlear Electrical Stimulation.

PubMed

Basta, Dietmar; Götze, Romy; Gröschel, Moritz; Jansen, Sebastian; Janke, Oliver; Tzschentke, Barbara; Boyle, Patrick; Ernst, Arne

2015-12-01

In recent years, cochlear implants have been applied successfully for the treatment of unilateral hearing loss with quite surprising benefit. One reason for this successful treatment, including the relief from tinnitus, could be the normalization of spontaneous activity in the central auditory pathway because of the electrical stimulation. The present study, therefore, investigated at a cellular level, the effect of a unilateral chronic intracochlear stimulation on key structures of the central auditory pathway. Normal-hearing guinea pigs were mechanically single-sided deafened through a standard HiFocus1j electrode array (on a HiRes 90k cochlear implant) being inserted into the first turn of the cochlea. Four to five electrode contacts could be used for the stimulation. Six weeks after surgery, the speech processor (Auria) was fitted, based on tNRI values and mounted on the animal's back. The two experimental groups were stimulated 16 hours per day for 90 days, using a HiRes strategy based on different stimulation rates (low rate (275 pps/ch), high rate (5000 pps/ch)). The results were compared with those of unilateral deafened controls (implanted but not stimulated), as well as between the treatment groups. All animals experienced a standardized free field auditory environment. The low-rate group showed a significantly lower average spontaneous activity bilaterally in the dorsal cochlear nucleus and the medial geniculate body than the controls. However, there was no difference in the inferior colliculus and the primary auditory cortex. Spontaneous activity of the high-rate group was also reduced bilaterally in the dorsal cochlear nucleus and in the primary auditory cortex. No differences could be observed between the high-rate group and the controls in the contra-lateral inferior colliculus and medial geniculate body. The high-rate group showed bilaterally a higher activity in the CN and the MGB compared with the low-rate group, whereas in the IC and in the AC a trend for an opposite effect could be determined. Unilateral intracochlear electrical stimulation seems to facilitate the homeostasis of the network activity, since it decreases the spontaneous activity that is usually elevated upon deafferentiation. The electrical stimulation per se seems to be responsible for the bilateral changes described above, rather than the particular nature of the electrical stimulation (e.g., rate). The normalization effects of electrical stimulation found in the present study are of particular importance in cochlear implant recipients with single-sided deafness.
Recognition and Localization of Speech by Adult Cochlear Implant Recipients Wearing a Digital Hearing Aid in the Nonimplanted Ear (Bimodal Hearing)

PubMed Central

Potts, Lisa G.; Skinner, Margaret W.; Litovsky, Ruth A.; Strube, Michael J; Kuk, Francis

2010-01-01

Background The use of bilateral amplification is now common clinical practice for hearing aid users but not for cochlear implant recipients. In the past, most cochlear implant recipients were implanted in one ear and wore only a monaural cochlear implant processor. There has been recent interest in benefits arising from bilateral stimulation that may be present for cochlear implant recipients. One option for bilateral stimulation is the use of a cochlear implant in one ear and a hearing aid in the opposite nonimplanted ear (bimodal hearing). Purpose This study evaluated the effect of wearing a cochlear implant in one ear and a digital hearing aid in the opposite ear on speech recognition and localization. Research Design A repeated-measures correlational study was completed. Study Sample Nineteen adult Cochlear Nucleus 24 implant recipients participated in the study. Intervention The participants were fit with a Widex Senso Vita 38 hearing aid to achieve maximum audibility and comfort within their dynamic range. Data Collection and Analysis Soundfield thresholds, loudness growth, speech recognition, localization, and subjective questionnaires were obtained six–eight weeks after the hearing aid fitting. Testing was completed in three conditions: hearing aid only, cochlear implant only, and cochlear implant and hearing aid (bimodal). All tests were repeated four weeks after the first test session. Repeated-measures analysis of variance was used to analyze the data. Significant effects were further examined using pairwise comparison of means or in the case of continuous moderators, regression analyses. The speech-recognition and localization tasks were unique, in that a speech stimulus presented from a variety of roaming azimuths (140 degree loudspeaker array) was used. Results Performance in the bimodal condition was significantly better for speech recognition and localization compared to the cochlear implant–only and hearing aid–only conditions. Performance was also different between these conditions when the location (i.e., side of the loudspeaker array that presented the word) was analyzed. In the bimodal condition, the speech-recognition and localization tasks were equal regardless of which side of the loudspeaker array presented the word, while performance was significantly poorer for the monaural conditions (hearing aid only and cochlear implant only) when the words were presented on the side with no stimulation. Binaural loudness summation of 1–3 dB was seen in soundfield thresholds and loudness growth in the bimodal condition. Measures of the audibility of sound with the hearing aid, including unaided thresholds, soundfield thresholds, and the Speech Intelligibility Index, were significant moderators of speech recognition and localization. Based on the questionnaire responses, participants showed a strong preference for bimodal stimulation. Conclusions These findings suggest that a well-fit digital hearing aid worn in conjunction with a cochlear implant is beneficial to speech recognition and localization. The dynamic test procedures used in this study illustrate the importance of bilateral hearing for locating, identifying, and switching attention between multiple speakers. It is recommended that unilateral cochlear implant recipients, with measurable unaided hearing thresholds, be fit with a hearing aid. PMID:19594084
Speech perception comparisons using an implanted and an external microphone in existing cochlear implant users.

PubMed

Jenkins, Herman A; Uhler, Kristin

2012-01-01

To compare the speech understanding abilities of cochlear implant listeners using 2 microphone technologies, the Otologics fully implantable Carina and the Cochlear Freedom microphones. Feasibility study using direct comparison of the 2 microphones, nonrandomized and nonblinded within case studies. Tertiary referral center hospital outpatient clinic. Four subjects with greater than 1 year of unilateral listening experience with the Freedom Cochlear Implant and a CNC word score higher than 40%. A Carina microphone coupled to a percutaneous plug was implanted on the ipsilateral side of the cochlear implant. Two months were allowed for healing before connecting to the Carina microphone. The percutaneous plug was connected to a body worn external processor with output leads inserted into the auxiliary port of the Freedom processor. Subjects were instructed to use each of the 2 microphones for half of their daily implant use. Aided pure tone thresholds, consonant-nucleus-consonant (CNC), Bamford-Kowel-Bench Speech in Noise test (BKN-SIN), and Abbreviated Profile of Hearing Aid Benefit. All subjects had sound perceptions using both microphones. The loudness and quality of the sound was judged to be poorer with the Carina in the first 2 subjects. The latter 2 demonstrated essential equivalence in the second two listeners, with the exception of the Abbreviated Profile of Hearing Aid Benefit reporting greater percentage of problems for the Carina in the background noise situation for subject 0011-003PP. CNC word scores were better with the Freedom than the Carina in all 4 subjects. The latter 2 showed improved speech perception abilities with the Carina, compared with the first 2. The BKB-SIN showed consistently better results with the Freedom in noise. Early observations indicate that it is potentially feasible to use the fully implanted Carina microphone with the Freedom Cochlear Implant. The authors would anticipate that outcomes would improve as more knowledge is gained in signal processing and with the fabrication of an integrated device.
Prevention and Treatment of Noise-Induced Tinnitus

DTIC Science & Technology

2012-07-01

process of completing the normative data base(s) of VGLUT1 , VAT and VGAT immunostaining in the rat AVCN and DCN that will allow assessment of changes under...our experimental conditions. Initial results indicate some loss of VGLUT1 immunolabeled auditory nerve terminals in the ventral cochlear nucleus...Research Accomplishments for TASK 3: Test the hypothesis that the loss of AN terminals (marked by VGLUT1 immunolabel) on neurons in the AVCN and
Converted and upgraded maps programmed in the newer speech processor for the first generation of multichannel cochlear implant.

PubMed

Magalhães, Ana Tereza de Matos; Goffi-Gomez, M Valéria Schmidt; Hoshino, Ana Cristina; Tsuji, Robinson Koji; Bento, Ricardo Ferreira; Brito, Rubens

2013-09-01

To identify the technological contributions of the newer version of speech processor to the first generation of multichannel cochlear implant and the satisfaction of users of the new technology. Among the new features available, we focused on the effect of the frequency allocation table, the T-SPL and C-SPL, and the preprocessing gain adjustments (adaptive dynamic range optimization). Prospective exploratory study. Cochlear implant center at hospital. Cochlear implant users of the Spectra processor with speech recognition in closed set. Seventeen patients were selected between the ages of 15 and 82 and deployed for more than 8 years. The technology update of the speech processor for the Nucleus 22. To determine Freedom's contribution, thresholds and speech perception tests were performed with the last map used with the Spectra and the maps created for Freedom. To identify the effect of the frequency allocation table, both upgraded and converted maps were programmed. One map was programmed with 25 dB T-SPL and 65 dB C-SPL and the other map with adaptive dynamic range optimization. To assess satisfaction, SADL and APHAB were used. All speech perception tests and all sound field thresholds were statistically better with the new speech processor; 64.7% of patients preferred maintaining the same frequency table that was suggested for the older processor. The sound field threshold was statistically significant at 500, 1,000, 1,500, and 2,000 Hz with 25 dB T-SPL/65 dB C-SPL. Regarding patient's satisfaction, there was a statistically significant improvement, only in the subscale of speech in noise abilities and phone use. The new technology improved the performance of patients with the first generation of multichannel cochlear implant.
Effect of input compression and input frequency response on music perception in cochlear implant users.

PubMed

Halliwell, Emily R; Jones, Linor L; Fraser, Matthew; Lockley, Morag; Hill-Feltham, Penelope; McKay, Colette M

2015-06-01

A study was conducted to determine whether modifications to input compression and input frequency response characteristics can improve music-listening satisfaction in cochlear implant users. Experiment 1 compared three pre-processed versions of music and speech stimuli in a laboratory setting: original, compressed, and flattened frequency response. Music excerpts comprised three music genres (classical, country, and jazz), and a running speech excerpt was compared. Experiment 2 implemented a flattened input frequency response in the speech processor program. In a take-home trial, participants compared unaltered and flattened frequency responses. Ten and twelve adult Nucleus Freedom cochlear implant users participated in Experiments 1 and 2, respectively. Experiment 1 revealed a significant preference for music stimuli with a flattened frequency response compared to both original and compressed stimuli, whereas there was a significant preference for the original (rising) frequency response for speech stimuli. Experiment 2 revealed no significant mean preference for the flattened frequency response, with 9 of 11 subjects preferring the rising frequency response. Input compression did not alter music enjoyment. Comparison of the two experiments indicated that individual frequency response preferences may depend on the genre or familiarity, and particularly whether the music contained lyrics.
Auditory Environment Across the Life Span of Cochlear Implant Users: Insights From Data Logging.

PubMed

Busch, Tobias; Vanpoucke, Filiep; van Wieringen, Astrid

2017-05-24

We describe the natural auditory environment of people with cochlear implants (CIs), how it changes across the life span, and how it varies between individuals. We performed a retrospective cross-sectional analysis of Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from 1,501 people with CIs (ages 0-96 years). They covered over 2.4 million hr of implant use and indicated how much time the CI users had spent in various acoustical environments. We investigated exposure to spoken language, noise, music, and quiet, and analyzed variation between age groups, users, and countries. CI users spent a substantial part of their daily life in noisy environments. As a consequence, most speech was presented in background noise. We found significant differences between age groups for all auditory scenes. Yet even within the same age group and country, variability between individuals was substantial. Regardless of their age, people with CIs face challenging acoustical environments in their daily life. Our results underline the importance of supporting them with assistive listening technology. Moreover, we found large differences between individuals' auditory diets that might contribute to differences in rehabilitation outcomes. Their causes and effects should be investigated further.
Comprehensive analysis of cochlear implant failure: usefulness of clinical symptom-based algorithm combined with in situ integrity testing.

PubMed

Yamazaki, Hiroshi; O'Leary, Stephen; Moran, Michelle; Briggs, Robert

2014-04-01

Accurate diagnosis of cochlear implant failures is important for management; however, appropriate strategies to assess possible device failures are not always clear. The purpose of this study is to understand correlation between causes of device failure and the presenting clinical symptoms as well as results of in situ integrity testing and to propose effective strategies for diagnosis of device failure. Retrospective case review. Cochlear implant center at a tertiary referral hospital. Twenty-seven cases with suspected device failure of Cochlear Nucleus systems (excluding CI512 failures) on the basis of deterioration in auditory perception from January 2000 to September 2012 in the Melbourne cochlear implant clinic. Clinical presentations and types of abnormalities on in situ integrity testing were compared with modes of device failure detected by returned device analysis. Sudden deterioration in auditory perception was always observed in cases with "critical damage": either fracture of the integrated circuit or most or all of the electrode wires. Subacute or gradually progressive deterioration in auditory perception was significantly associated with a more limited number of broken electrode wires. Cochlear implant mediated auditory and nonauditory symptoms were significantly associated with an insulation problem. An algorithm based on the time course of deterioration in auditory perception and cochlear implant-mediated auditory and nonauditory symptoms was developed on the basis of these retrospective analyses, to help predict the mode of device failure. In situ integrity testing, which included close monitoring of device function in routine programming sessions as well as repeating the manufacturer's integrity test battery, was sensitive enough to detect malfunction in all suspected device failures, and each mode of device failure showed a characteristic abnormality on in situ integrity testing. Our clinical manifestation-based algorithm combined with in situ integrity testing may be useful for accurate diagnosis and appropriate management of device failure. Close monitoring of device function in routine programming sessions as well as repeating the manufacturer's integrity test battery is important if the initial in situ integrity testing is inconclusive because objective evidence of failure in the implanted device is essential to recommend explantation/reimplantation.
Cytomegalovirus induced sensorineural hearing loss with persistent cochlear inflammation in neonatal mice

PubMed Central

Schachtele, Scott J.; Mutnal, Manohar B.; Schleiss, Mark R.; Lokensgard, James R.

2011-01-01

Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL) in children. During murine (M)CMV-induced encephalitis, the immune response is important for both the control of viral dissemination and the clearance of virus from the brain. While the importance of CMV-induced SNHL has been described, the mechanisms surrounding its pathogenesis and the role of inflammatory responses remain unclear. This study presents a neonatal mouse model of profound SNHL in which MCMV preferentially infected both cochlear perilymphatic epithelial cells and spiral ganglion neurons. Interestingly, MCMV infection induced cochlear hair cell death by 21 days post-infection, despite a clear lack of direct infection of hair cells and the complete clearance of the virus from the cochlea by 14 dpi. Flow cytometric, immunohistochemical, and quantitative PCR analysis of MCMV-infected cochlea revealed a robust and chronic inflammatory response, including a prolonged increase in reactive oxygen species production by infiltrating macrophages. These data support a pivotal role for inflammation during MCMV-induced SNHL. PMID:21416394
Cytomegalovirus-induced sensorineural hearing loss with persistent cochlear inflammation in neonatal mice.

PubMed

Schachtele, Scott J; Mutnal, Manohar B; Schleiss, Mark R; Lokensgard, James R

2011-06-01

Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL) in children. During murine (M)CMV-induced encephalitis, the immune response is important for both the control of viral dissemination and the clearance of virus from the brain. While the importance of CMV-induced SNHL has been described, the mechanisms surrounding its pathogenesis and the role of inflammatory responses remain unclear. This study presents a neonatal mouse model of profound SNHL in which MCMV preferentially infected both cochlear perilymphatic epithelial cells and spiral ganglion neurons. Interestingly, MCMV infection induced cochlear hair cell death by 21 days post-infection, despite a clear lack of direct infection of hair cells and the complete clearance of the virus from the cochlea by 14 dpi. Flow cytometric, immunohistochemical, and quantitative PCR analysis of MCMV-infected cochlea revealed a robust and chronic inflammatory response, including a prolonged increase in reactive oxygen species production by infiltrating macrophages. These data support a pivotal role for inflammation during MCMV-induced SNHL.
d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity

PubMed Central

Kirkwood, Nerissa K.; O'Reilly, Molly; Derudas, Marco; Kenyon, Emma J.; Huckvale, Rosemary; van Netten, Sietse M.; Ward, Simon E.; Richardson, Guy P.; Kros, Corné J.

2017-01-01

Aminoglycoside antibiotics are widely used for the treatment of life-threatening bacterial infections, but cause permanent hearing loss in a substantial proportion of treated patients. The sensory hair cells of the inner ear are damaged following entry of these antibiotics via the mechano-electrical transducer (MET) channels located at the tips of the hair cell's stereocilia. d-Tubocurarine (dTC) is a MET channel blocker that reduces the loading of gentamicin-Texas Red (GTTR) into rat cochlear hair cells and protects them from gentamicin treatment. Berbamine is a structurally related alkaloid that reduces GTTR labeling of zebrafish lateral-line hair cells and protects them from aminoglycoside-induced cell death. Both compounds are thought to reduce aminoglycoside entry into hair cells through the MET channels. Here we show that dTC (≥6.25 μM) or berbamine (≥1.55 μM) protect zebrafish hair cells in vivo from neomycin (6.25 μM, 1 h). Protection of zebrafish hair cells against gentamicin (10 μM, 6 h) was provided by ≥25 μM dTC or ≥12.5 μM berbamine. Hair cells in mouse cochlear cultures are protected from longer-term exposure to gentamicin (5 μM, 48 h) by 20 μM berbamine or 25 μM dTC. Berbamine is, however, highly toxic to mouse cochlear hair cells at higher concentrations (≥30 μM) whilst dTC is not. The absence of toxicity in the zebrafish assays prompts caution in extrapolating results from zebrafish neuromasts to mammalian cochlear hair cells. MET current recordings from mouse outer hair cells (OHCs) show that both compounds are permeant open-channel blockers, rapidly and reversibly blocking the MET channel with half-blocking concentrations of 2.2 μM (dTC) and 2.8 μM (berbamine) in the presence of 1.3 mM Ca2+ at −104 mV. Berbamine, but not dTC, also blocks the hair cell's basolateral K+ current, IK,neo, and modeling studies indicate that berbamine permeates the MET channel more readily than dTC. These studies reveal key properties of MET-channel blockers required for the future design of successful otoprotectants. PMID:28928635
A rapid form of activity-dependent recovery from short-term synaptic depression in the intensity pathway of the auditory brainstem

PubMed Central

Horiuchi, Timothy K.

2011-01-01

Short-term synaptic plasticity acts as a time- and firing rate-dependent filter that mediates the transmission of information across synapses. In the avian auditory brainstem, specific forms of plasticity are expressed at different terminals of the same auditory nerve fibers and contribute to the divergence of acoustic timing and intensity information. To identify key differences in the plasticity properties, we made patch-clamp recordings from neurons in the cochlear nucleus responsible for intensity coding, nucleus angularis, and measured the time course of the recovery of excitatory postsynaptic currents following short-term synaptic depression. These synaptic responses showed a very rapid recovery, following a bi-exponential time course with a fast time constant of ~40 ms and a dependence on the presynaptic activity levels, resulting in a crossing over of the recovery trajectories following high-rate versus low-rate stimulation trains. We also show that the recorded recovery in the intensity pathway differs from similar recordings in the timing pathway, specifically the cochlear nucleus magnocellularis, in two ways: (1) a fast recovery that was not due to recovery from postsynaptic receptor desensitization and (2) a recovery trajectory that was characterized by a non-monotonic bump that may be due in part to facilitation mechanisms more prevalent in the intensity pathway. We tested whether a previously proposed model of synaptic transmission based on vesicle depletion and sequential steps of vesicle replenishment could account for the recovery responses, and found it was insufficient, suggesting an activity-dependent feedback mechanism is present. We propose that the rapid recovery following depression allows improved coding of natural auditory signals that often consist of sound bursts separated by short gaps. PMID:21409439
Revision surgery due to magnet dislocation in cochlear implant patients: an emerging complication.

PubMed

Hassepass, Frederike; Stabenau, Vanessa; Maier, Wolfgang; Arndt, Susan; Laszig, Roland; Beck, Rainer; Aschendorff, Antje

2014-01-01

To analyze the cause and effect of magnet dislocation in cochlear implant (CI) recipients requiring magnet revision surgery for treatment. Retrospective study. Tertiary referral center. Case reports from 1,706 CI recipients consecutively implanted from January 2000 to December 2011 were reviewed. The number of cases requiring magnet revision surgery was assessed. Revision surgery involving magnet removal or replacement was indicated in 1.23% (21/1,706), of all CI recipients. Magnet dislocation occurring during magnetic resonance tomography (MRI), at 1.5 Tesla (T), with the magnet in place and with the application of compression bandaging around the head, was the main cause for revision surgery in 47.62% (10/21) of the affected cases. All 10 cases were implanted with Cochlear Nucleus cochlear implants. These events occurred, despite adherence to current recommendations of the manufacturer. The present study underlines that MRI examination is the main cause of magnet dislocation. The use of compressive bandaging when using 1.5-T MRI does not eliminate the risk of magnet dislocation. Additional cautionary measures are for required for conditional MRI. We recommend X-ray examination after MRI to determine magnet dislocation and avoid major complications in all cases reporting pain during or after MRI. Additional research regarding silicon magnet pocket design for added retention is needed. Effective communication of guidelines for precautionary measures during MRI examination in CI patients is mandatory for all clinicians involved. MRI in CI recipients should be indicated with caution.
Cytomegalovirus (CMV) Infection Causes Degeneration of Cochlear Vasculature and Hearing Loss in a Mouse Model.

PubMed

Carraro, Mattia; Almishaal, Ali; Hillas, Elaine; Firpo, Matthew; Park, Albert; Harrison, Robert V

2017-04-01

Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children. We have used a murine model of CMV infection to reveal functional and structural cochlear pathogenesis. The cerebral cortex of Balb/c mice (Mus musculus) was inoculated with 2000 pfu (plaque forming units) of murine CMV on postnatal day 3. At 6 weeks of age, cochlear function was monitored using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measures. Histological assessment of cochlear vasculature using a corrosion cast technique was made at 8 weeks. Vascular casts of mCMV-damaged cochleas, and those of untreated control animals, were examined using scanning electron microscopy. We find very large variations in the degree of vascular damage in animals given identical viral injections (2000 pfu). The primary lesion caused by CMV infection is to the stria vascularis and to the adjacent spiral limbus capillary network. Capillary beds of the spiral ligament are generally less affected. The initial vascular damage is found in the mid-apical turn and appears to progress to more basal cochlear regions. After viral migration to the inner ear, the stria vascularis is the primary affected structure. We suggest that initial auditory threshold losses may relate to the poor development or maintenance of the endocochlear potential caused by strial dysfunction. Our increased understanding of the pathogenesis of CMV-related hearing loss is important for defining methods for early detection and treatment.
Engraftment and Differentiation of Embryonic Stem Cell–Derived Neural Progenitor Cells in the Cochlear Nerve Trunk: Growth of Processes into the Organ of Corti

PubMed Central

Corrales, C. Eduardo; Pan, Luying; Li, Huawei; Liberman, M. Charles; Heller, Stefan; Edge, Albert S.B.

2007-01-01

Hearing loss in mammals is irreversible because cochlear neurons and hair cells do not regenerate. To determine whether we could replace neurons lost to primary neuronal degeneration, we injected EYFP-expressing embryonic stem cell–derived mouse neural progenitor cells into the cochlear nerve trunk in immunosuppressed animals 1 week after destroying the cochlear nerve (spiral ganglion) cells while leaving hair cells intact by ouabain application to the round window at the base of the cochlea in gerbils. At 3 days post transplantation, small grafts were seen that expressed endogenous EYFP and could be immunolabeled for neuron-specific markers. Twelve days after transplantation, the grafts had neurons that extended processes from the nerve core toward the denervated organ of Corti. By 64–98 days, the grafts had sent out abundant processes that occupied a significant portion of the space formerly occupied by the cochlear nerve. The neurites grew in fasciculating bundles projecting through Rosenthal’s canal, the former site of spiral ganglion cells, into the osseous spiral lamina and ultimately into the organ of Corti, where they contacted hair cells. Neuronal counts showed a significant increase in neuronal processes near the sensory epithelium, compared to animals that were denervated without subsequent stem cell transplantation. The regeneration of these neurons shows that neurons differentiated from stem cells have the capacity to grow to a specific target in an animal model of neuronal degeneration. PMID:17013931
Sox10 Expressing Cells in the Lateral Wall of the Aged Mouse and Human Cochlea

PubMed Central

Hao, Xinping; Xing, Yazhi; Moore, Michael W.; Zhang, Jianning; Han, Demin; Schulte, Bradley A.; Dubno, Judy R.; Lang, Hainan

2014-01-01

Age-related hearing loss (presbycusis) is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1–3 month-old) and aged (2–2.5 year-old) mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells) in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the aged ear. PMID:24887110
Peroxynitrite induces apoptosis of mouse cochlear hair cells via a Caspase-independent pathway in vitro.

PubMed

Cao, Zhixin; Yang, Qianqian; Yin, Haiyan; Qi, Qi; Li, Hongrui; Sun, Gaoying; Wang, Hongliang; Liu, Wenwen; Li, Jianfeng

2017-11-01

Peroxynitrite (ONOO - ) is a potent and versatile oxidant implicated in a number of pathophysiological processes. The present study was designed to investigate the effect of ONOO - on the cultured cochlear hair cells (HCs) of C57BL/6 mice in vitro as well as the possible mechanism underlying the action of such an oxidative stress. The in vitro primary cultured cochlear HCs were subjected to different concentrations of ONOO - , then, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy (TEM), the apoptosis was determined by Terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) assay, the mRNA expressions of Caspase-3, Caspase-8, Caspase-9, Apaf1, Bcl-2, and Bax were analyzed by RT-PCR, and the protein expressions of Caspase-3 and AIF were assessed by immunofluorescence. This work demonstrated that direct exposure of primary cultured cochlear HCs to ONOO - could result in a base-to-apex gradient injury of HCs in a concentration-dependent manner. Furthermore, ONOO - led to much more losses of outer hair cells than inner hair cells mainly through the induction of apoptosis of HCs as evidenced by TEM and TUNEL assays. The mRNA expressions of Caspase-8, Caspase-9, Apaf1, and Bax were increased and, meanwhile, the mRNA expression of Bcl-2 was decreased in response to ONOO - treatment. Of interesting, the expression of Caspase-3 had no significant change, whereas, the expression alteration of AIF was observed. These results suggested that ONOO - can effectively damage the survival of cochlear HCs via triggering the apoptotic pathway. The findings from this work suggest that ONOO - -induced apoptosis is mediated, at least in part, via a Caspase-independent pathway in cochlear HCs.

Embryonic Origins of the Mouse Superior Olivary Complex

PubMed Central

Howell, David M.; Spirou, George A.; Mathers, Peter H.

2014-01-01

Many areas of the central nervous system are organized into clusters of cell groups, with component cell groups exhibiting diverse but related functions. One such cluster, the superior olivary complex (SOC), is located in the ventral auditory brainstem in mammals. The SOC is an obligatory contact point for most projection neurons of the ventral cochlear nucleus and plays central roles in many aspects of monaural and binaural information processing. Despite their important interrelated functions, little is known about the embryonic origins of SOC nuclei, due in part to a paucity of developmental markers to distinguish individual cell groups. In this report, we present a collection of novel markers for the developing SOC nuclei in mice, including the transcription factors FoxP1, MafB, and Sox2, and the lineage-marking transgenic line En1-Cre. We use these definitive markers to examine the rhombic lip and rhombomeric origins of SOC nuclei and demonstrate that they can serve to uniquely identify SOC nuclei and subnuclei in newborn pups. The markers are also useful in identifying distinct nuclear domains within the presumptive SOC as early as embryonic day (E) 14.5, well before morphological distinction of individual nuclei is evident. These findings indicate that the mediolateral and dorsoventral position of SOC nuclei characteristic of the adult brainstem is established during early neurogenesis. PMID:23303740
Ipsilateral masking between acoustic and electric stimulations.

PubMed

Lin, Payton; Turner, Christopher W; Gantz, Bruce J; Djalilian, Hamid R; Zeng, Fan-Gang

2011-08-01

Residual acoustic hearing can be preserved in the same ear following cochlear implantation with minimally traumatic surgical techniques and short-electrode arrays. The combined electric-acoustic stimulation significantly improves cochlear implant performance, particularly speech recognition in noise. The present study measures simultaneous masking by electric pulses on acoustic pure tones, or vice versa, to investigate electric-acoustic interactions and their underlying psychophysical mechanisms. Six subjects, with acoustic hearing preserved at low frequencies in their implanted ear, participated in the study. One subject had a fully inserted 24 mm Nucleus Freedom array and five subjects had Iowa/Nucleus hybrid implants that were only 10 mm in length. Electric masking data of the long-electrode subject showed that stimulation from the most apical electrodes produced threshold elevations over 10 dB for 500, 625, and 750 Hz probe tones, but no elevation for 125 and 250 Hz tones. On the contrary, electric stimulation did not produce any electric masking in the short-electrode subjects. In the acoustic masking experiment, 125-750 Hz pure tones were used to acoustically mask electric stimulation. The acoustic masking results showed that, independent of pure tone frequency, both long- and short-electrode subjects showed threshold elevations at apical and basal electrodes. The present results can be interpreted in terms of underlying physiological mechanisms related to either place-dependent peripheral masking or place-independent central masking.
Slow Cholinergic Modulation of Spike Probability in Ultra-Fast Time-Coding Sensory Neurons

PubMed Central

Goyer, David; Kurth, Stefanie; Rübsamen, Rudolf

2016-01-01

Abstract Sensory processing in the lower auditory pathway is generally considered to be rigid and thus less subject to modulation than central processing. However, in addition to the powerful bottom-up excitation by auditory nerve fibers, the ventral cochlear nucleus also receives efferent cholinergic innervation from both auditory and nonauditory top–down sources. We thus tested the influence of cholinergic modulation on highly precise time-coding neurons in the cochlear nucleus of the Mongolian gerbil. By combining electrophysiological recordings with pharmacological application in vitro and in vivo, we found 55–72% of spherical bushy cells (SBCs) to be depolarized by carbachol on two time scales, ranging from hundreds of milliseconds to minutes. These effects were mediated by nicotinic and muscarinic acetylcholine receptors, respectively. Pharmacological block of muscarinic receptors hyperpolarized the resting membrane potential, suggesting a novel mechanism of setting the resting membrane potential for SBC. The cholinergic depolarization led to an increase of spike probability in SBCs without compromising the temporal precision of the SBC output in vitro. In vivo, iontophoretic application of carbachol resulted in an increase in spontaneous SBC activity. The inclusion of cholinergic modulation in an SBC model predicted an expansion of the dynamic range of sound responses and increased temporal acuity. Our results thus suggest of a top–down modulatory system mediated by acetylcholine which influences temporally precise information processing in the lower auditory pathway. PMID:27699207
Auditory Brainstem Circuits That Mediate the Middle Ear Muscle Reflex

PubMed Central

Mukerji, Sudeep; Windsor, Alanna Marie; Lee, Daniel J.

2010-01-01

The middle ear muscle (MEM) reflex is one of two major descending systems to the auditory periphery. There are two middle ear muscles (MEMs): the stapedius and the tensor tympani. In man, the stapedius contracts in response to intense low frequency acoustic stimuli, exerting forces perpendicular to the stapes superstructure, increasing middle ear impedance and attenuating the intensity of sound energy reaching the inner ear (cochlea). The tensor tympani is believed to contract in response to self-generated noise (chewing, swallowing) and nonauditory stimuli. The MEM reflex pathways begin with sound presented to the ear. Transduction of sound occurs in the cochlea, resulting in an action potential that is transmitted along the auditory nerve to the cochlear nucleus in the brainstem (the first relay station for all ascending sound information originating in the ear). Unknown interneurons in the ventral cochlear nucleus project either directly or indirectly to MEM motoneurons located elsewhere in the brainstem. Motoneurons provide efferent innervation to the MEMs. Although the ascending and descending limbs of these reflex pathways have been well characterized, the identity of the reflex interneurons is not known, as are the source of modulatory inputs to these pathways. The aim of this article is to (a) provide an overview of MEM reflex anatomy and physiology, (b) present new data on MEM reflex anatomy and physiology from our laboratory and others, and (c) describe the clinical implications of our research. PMID:20870664
Usefulness of Intravital Multiphoton Microscopy in Visualizing Study of Mouse Cochlea and Volume Changes in the Scala Media

PubMed Central

Ju, Hyun Mi; Lee, Sun Hee; Kong, Tae Hoon; Kwon, Seung-Hae; Choi, Jin Sil; Seo, Young Joon

2017-01-01

Conventional microscopy has limitations in viewing the cochlear microstructures due to three-dimensional spiral structure and the overlying bone. But these issues can be overcome by imaging the cochlea in vitro with intravital multiphoton microscopy (MPM). By using near-infrared lasers for multiphoton excitation, intravital MPM can detect endogenous fluorescence and second harmonic generation of tissues. In this study, we used intravital MPM to visualize various cochlear microstructures without any staining and non-invasively analyze the volume changes of the scala media (SM) without removing the overlying cochlear bone. The intravital MPM images revealed various tissue types, ranging from thin membranes to dense bone, as well as the spiral ganglion beneath the cochlear bone. The two-dimensional, cross-sectional, and serial z-stack intravital MPM images also revealed the spatial dilation of the SM in the temporal bone of pendrin-deficient mice. These findings suggest that intravital MPM might serve as a new method for obtaining microanatomical information regarding the cochlea, similar to standard histopathological analyses in the animal study for the cochlea. Given the capability of intravital MPM for detecting an increase in the volume of the SM in pendrin-deficient mice, it might be a promising new tool for assessing the pathophysiology of hearing loss in the future. PMID:28824523
Usefulness of Intravital Multiphoton Microscopy in Visualizing Study of Mouse Cochlea and Volume Changes in the Scala Media.

PubMed

Ju, Hyun Mi; Lee, Sun Hee; Kong, Tae Hoon; Kwon, Seung-Hae; Choi, Jin Sil; Seo, Young Joon

2017-01-01

Conventional microscopy has limitations in viewing the cochlear microstructures due to three-dimensional spiral structure and the overlying bone. But these issues can be overcome by imaging the cochlea in vitro with intravital multiphoton microscopy (MPM). By using near-infrared lasers for multiphoton excitation, intravital MPM can detect endogenous fluorescence and second harmonic generation of tissues. In this study, we used intravital MPM to visualize various cochlear microstructures without any staining and non-invasively analyze the volume changes of the scala media (SM) without removing the overlying cochlear bone. The intravital MPM images revealed various tissue types, ranging from thin membranes to dense bone, as well as the spiral ganglion beneath the cochlear bone. The two-dimensional, cross-sectional, and serial z-stack intravital MPM images also revealed the spatial dilation of the SM in the temporal bone of pendrin-deficient mice. These findings suggest that intravital MPM might serve as a new method for obtaining microanatomical information regarding the cochlea, similar to standard histopathological analyses in the animal study for the cochlea. Given the capability of intravital MPM for detecting an increase in the volume of the SM in pendrin-deficient mice, it might be a promising new tool for assessing the pathophysiology of hearing loss in the future.
Time-controllable Nkcc1 knockdown replicates reversible hearing loss in postnatal mice.

PubMed

Watabe, Takahisa; Xu, Ming; Watanabe, Miho; Nabekura, Junichi; Higuchi, Taiga; Hori, Karin; Sato, Mitsuo P; Nin, Fumiaki; Hibino, Hiroshi; Ogawa, Kaoru; Masuda, Masatsugu; Tanaka, Kenji F

2017-10-19

Identification of the causal effects of specific proteins on recurrent and partially reversible hearing loss has been difficult because of the lack of an animal model that provides reversible gene knockdown. We have developed the transgenic mouse line Actin-tTS::Nkcc1 tetO/tetO for manipulatable expression of the cochlear K + circulation protein, NKCC1. Nkcc1 transcription was blocked by the binding of a tetracycline-dependent transcriptional silencer to the tetracycline operator sequences inserted upstream of the Nkcc1 translation initiation site. Administration of the tetracycline derivative doxycycline reversibly regulated Nkcc1 knockdown. Progeny from pregnant/lactating mothers fed doxycycline-free chow from embryonic day 0 showed strong suppression of Nkcc1 expression (~90% downregulation) and Nkcc1 null phenotypes at postnatal day 35 (P35). P35 transgenic mice from mothers fed doxycycline-free chow starting at P0 (delivery) showed weaker suppression of Nkcc1 expression (~70% downregulation) and less hearing loss with mild cochlear structural changes. Treatment of these mice at P35 with doxycycline for 2 weeks reactivated Nkcc1 transcription to control levels and improved hearing level at high frequency; i.e., these doxycycline-treated mice exhibited partially reversible hearing loss. Thus, development of the Actin-tTS::Nkcc1 tetO/tetO transgenic mouse line provides a mouse model for the study of variable hearing loss through reversible knockdown of Nkcc1.
Phase contrast imaging of cochlear soft tissue.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, S.; Hwang, M.; Rau, C.

A noninvasive technique to image soft tissue could expedite diagnosis and disease management in the auditory system. We propose inline phase contrast imaging with hard X-rays as a novel method that overcomes the limitations of conventional absorption radiography for imaging soft tissue. In this study, phase contrast imaging of mouse cochleae was performed at the Argonne National Laboratory Advanced Photon Source. The phase contrast tomographic reconstructions show soft tissue structures of the cochlea, including the inner pillar cells, the inner spiral sulcus, the tectorial membrane, the basilar membrane, and the Reissner's membrane. The results suggest that phase contrast X-ray imagingmore » and tomographic techniques hold promise to noninvasively image cochlear structures at an unprecedented cellular level.« less
Binaural Speech Understanding With Bilateral Cochlear Implants in Reverberation.

PubMed

Kokkinakis, Kostas

2018-03-08

The purpose of this study was to investigate whether bilateral cochlear implant (CI) listeners who are fitted with clinical processors are able to benefit from binaural advantages under reverberant conditions. Another aim of this contribution was to determine whether the magnitude of each binaural advantage observed inside a highly reverberant environment differs significantly from the magnitude measured in a near-anechoic environment. Ten adults with postlingual deafness who are bilateral CI users fitted with either Nucleus 5 or Nucleus 6 clinical sound processors (Cochlear Corporation) participated in this study. Speech reception thresholds were measured in sound field and 2 different reverberation conditions (0.06 and 0.6 s) as a function of the listening condition (left, right, both) and the noise spatial location (left, front, right). The presence of the binaural effects of head-shadow, squelch, summation, and spatial release from masking in the 2 different reverberation conditions tested was determined using nonparametric statistical analysis. In the bilateral population tested, when the ambient reverberation time was equal to 0.6 s, results indicated strong positive effects of head-shadow and a weaker spatial release from masking advantage, whereas binaural squelch and summation contributed no statistically significant benefit to bilateral performance under this acoustic condition. These findings are consistent with those of previous studies, which have demonstrated that head-shadow yields the most pronounced advantage in noise. The finding that spatial release from masking produced little to almost no benefit in bilateral listeners is consistent with the hypothesis that additive reverberation degrades spatial cues and negatively affects binaural performance. The magnitude of 4 different binaural advantages was measured on the same group of bilateral CI subjects fitted with clinical processors in 2 different reverberation conditions. The results of this work demonstrate the impeding properties of reverberation on binaural speech understanding. In addition, results indicate that CI recipients who struggle in everyday listening environments are also more likely to benefit less in highly reverberant environments from their bilateral processors.
Clinical evaluation of higher stimulation rates in the nucleus research platform 8 system.

PubMed

Plant, Kerrie; Holden, Laura; Skinner, Margo; Arcaroli, Jennifer; Whitford, Lesley; Law, Mary-Ann; Nel, Esti

2007-06-01

The effect on speech perception of using higher stimulation rates than the 14.4 kHz available in the Nucleus 24 cochlear implant system was investigated. The study used the Nucleus Research Platform 8 (RP8) system, comprising the CI24RE receiver-stimulator with the Contour electrode array, the L34SP body-worn research speech processor, and the Nucleus Programming Environment (NPE) fitting and Neural Response Telemetry (NRT) software. This system enabled clinical investigation of higher stimulation rates before an implementation in the Freedom cochlear implant system commercially released by Cochlear Limited. Use of higher stimulation rates in the ACE coding strategy was assessed in 15 adult subjects. An ABAB experimental design was used to control for order effects. Program A used a total stimulation rate of between 12 kHz and 14.4 kHz. This program was used for at least the first 3 mo after initial device activation. After evaluation with this program, each subject was provided with two different higher stimulation rate programs: one with a total stimulation rate of 24 kHz and the other with a total stimulation rate of 32 kHz. After a 6-week period of familiarization, each subject identified his/her preferred higher rate program (program B), and this was used for the evaluation. Subjects then repeated their use of program A for 3 wk, then program B for 3 wk, before the second evaluation with each. Speech perception was evaluated by using CNC open-set monosyllabic words presented in quiet and CUNY open-set sentences presented in noise. Preference for stimulation rate program was assessed via a subjective questionnaire. Threshold (T)- and Comfortable (C)-levels, as well as subjective reports of tinnitus, were monitored for each subject throughout the study to determine whether there were any changes that might be associated with the use of higher stimulation rates. No significant mean differences in speech perception results were found for the group between the two programs for tests in either quiet or noise. Analysis of individual subject data showed that five subjects had significant benefit from use of program B for tests administered in quiet and for tests administered in noise. However, only two of these subjects showed benefit in both test conditions. One subject showed significant benefit from use of program A when tested in quiet, whereas another showed benefit with this program in noise. Each subject's preferred program varied. Five subjects reported a preference for program A, eight subjects reported a preference for program B and two reported no overall preference. Preference between the different stimulation rates provided within program B also varied, with 10 subjects preferring 24 kHz and five preferring 32 kHz total stimulation rates. A significant increase in T-levels from baseline measures was observed after three weeks of initial experience with program B, however there was no difference between the baseline levels and those obtained after five weeks of use. No significant change in C-levels was found over the monitoring period. No long-term changes in tinnitus that could be associated with the use of the higher stimulation rates were reported by any of the subjects. The use of higher stimulation rates may provide benefit to some but not all cochlear implant recipients. It is important to optimize the stimulation rate for an individual to ensure maximal benefit. The absence of any changes in T- and C-levels or in tinnitus suggests that higher stimulation rates are safe for clinical use.
Reimplantation with a conventional length electrode following residual hearing loss in four hybrid implant recipients

PubMed Central

Carlson, Matthew L; Archibald, David J; Gifford, Rene H; Driscoll, Colin LW; Beatty, Charles W

2014-01-01

Hypothesis Revision surgery using a newer-generation conventional length cochlear implant electrode will provide improved speech perception in patients that initially underwent hybrid electrode implantation and experienced post-operative loss of residual hearing and performance deterioration. Clinical presentation We present four patients who experienced delayed post-operative hearing loss following implantation with the Nucleus Hybrid S8 device and underwent reimplantation with the Nucleus Freedom or Nucleus 5 device using the Contour Advance array. Pure-tone thresholds and speech perception data were retrospectively reviewed. Intervention Four subjects underwent reimplantation with the Nucleus Freedom or Nucleus 5 device after experiencing deteriorating performance related to delayed acoustic hearing loss. Comparison of pre-revision performance to the most recent post-revision performance demonstrated improved speech perception performance in all subjects following reimplantation. Conclusions A small percent of patients will experience a significant loss of residual low-frequency hearing following hybrid implantation thereby becoming completely reliant on a shorter electrode for electrical stimulation. In the current series, reimplantation with a conventional length electrode provided improved speech perception performance in such patients. Revision surgery with a conventional length electrode should be considered in ‘short electrode’ recipients who experience performance deterioration following loss of residual hearing. PMID:22333755
Connections of the Auditory Brainstem in a Songbird, Taeniopygia guttata. III. Projections of the Superior Olive and Lateral Lemniscal Nuclei

PubMed Central

Wild, J. Martin; Krützfeldt, Nils O.E.; Kubke, M. Fabiana

2013-01-01

Sequential to companion articles that report the projections of the cochlear nucleus angularis (NA) and the third-order nucleus laminaris (NL) to the central nucleus of the inferior colliculus (MLd) and to the superior olive (OS) and lateral lemniscal nuclei (LLV, LLI, and LLD) (Krützfeldt et al., J Comp Neurol, this issue), we here describe the projections of the latter group of nuclei using standard tract-tracing methods. OS projects on LLV and both have further ascending projections on LLI, LLD, and MLd. LLV also provides auditory input to the song system, via nucleus uvaeformis, and to the thalamo-telencephalic auditory system, via nucleus ovoidalis (Ov), thus bypassing MLd. The two divisions of LLD (LLDa and LLDp) project across the midline via the commissure of Probst each to innervate the homologous contralateral nucleus and MLd. Both, particularly LLDp, also project on Ov. Injections in LLD and LLV resulted in anterograde labeling of caudal nucleus basorostralis (Bas) in the frontal telencephalon, but retrograde tracing so far suggests that only LLI is a real source of this projection (Wild and Farabaugh [1996] J Comp Neurol 365:306–328). OS and LLV also have descending projections on the ipsilateral NA, NM, and NL, and LLV also projects on OS. The ascending inputs to MLd and more rostral nuclei may contribute importantly to mechanisms of auditory pattern (song) recognition. Consistent with previous studies, some of the descending projections may be inhibitory. PMID:20394063
A Comparative Study of Drug Delivery Methods Targeted to the Mouse Inner Ear: Bullostomy Versus Transtympanic Injection

PubMed Central

Cediel, Rafael; Celaya, Adelaida M.; Lassaletta, Luis; Varela-Nieto, Isabel; Contreras, Julio

2017-01-01

We present two minimally invasive microsurgical techniques in rodents for specific drug delivery into the middle ear so that it may reach the inner ear. The first procedure consists of perforation of the tympanic bulla, termed bullostomy; the second one is a transtympanic injection. Both emulate human clinical intratympanic procedures. Chitosan-glycerophosphate (CGP) and Ringer´s Lactate buffer (RL) were used as biocompatible vehicles for local drug delivery. CGP is a nontoxic biodegradable polymer widely used in pharmaceutical applications. It is a viscous liquid at RT but it congeals to a semi solid phase at body temperature. RL is an isotonic solution used for intravenous administrations in humans. A small volume of this vehicle is precisely placed on the Round Window (RW) niche by means of a bullostomy. A transtympanic injection fills the middle ear and allows less control but broader access to the inner ear. The safety profiles of both techniques were studied and compared by using functional and morphological tests. Hearing was evaluated by registering the Auditory Brainstem Response (ABR) before and several times after microsurgery. The cytoarchitecture and preservation level of cochlear structures were studied by conventional histological techniques in paraformaldehyde-fixed and decalcified cochlear samples. In parallel, unfixed cochlear samples were taken and immediately frozen to analyze gene expression profiles of inflammatory markers by quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). Both procedures are suitable as drug delivery methods into the mouse middle ear, although transtympanic injection proved to be less invasive compared to bullostomy. PMID:28362376
The mouse cochlea expresses a local hypothalamic-pituitary-adrenal equivalent signaling system and requires CRFR1 to establish normal hair cell innervation and cochlear sensitivity

PubMed Central

Graham, Christine E.; Vetter, Douglas E.

2011-01-01

Cells of the inner ear face constant metabolic and structural stress. Exposure to intense sound or certain drugs destroys cochlea hair cells, which in mammals do not regenerate. Thus, an endogenous stress response system may exist within the cochlea to protect it from everyday stressors. We recently described the existence of Corticotropin-Releasing Factor (CRF) in the mouse cochlea. The CRFR1 receptor is considered the primary and canonical target of CRF signaling, and systemically it plays an essential role in coordinating the body-wide stress response via activation of the hypothalamic-pituitary-adrenal (HPA) axis. Here we describe an essential role for CRFR1 in auditory system development and function, and offer the first description of a complete HPA equivalent signaling system resident within the cochlea. To reveal the role of CRFR1 activation in the cochlea, we have used mice carrying a null ablation of the CRFR1 gene. CRFR1−/− mice exhibited elevated auditory thresholds at all frequencies tested, indicating reduced sensitivity. Furthermore, our results suggest that CRFR1 has a developmental role affecting inner hair cell morphology and afferent and efferent synapse distribution. Given the role of HPA signaling in maintaining local homeostasis in other tissues, the presence of a cochlear HPA signaling system suggests important roles for CRFR1 activity in setting cochlear sensitivity, perhaps both neural and non-neural mechanisms. These data highlight the complex pleiotropic mechanisms modulated by CRFR1 signaling in the cochlea. PMID:21273411
Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.

PubMed

Maier, Jennifer A; Harfe, Brian D

2011-11-15

The transition of the mouse embryonic notochord into nuclei pulposi was determined ("fate mapped") in vivo in growth and differentiating factor-5 (GDF-5)-null mice using the Shhcre and R26R alleles. To determine whether abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5-null mice. The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5-null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5-null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or result from progressive postnatal degeneration of nuclei pulposi. Gdf-5 messenger RNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5-null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24-week-old mice. Our Gdf-5 messenger RNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate-mapping experiments revealed that notochord cells in Gdf-5-null mice correctly form nuclei pulposi. Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5-null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects.
Nuclei pulposi formation from the embryonic notochord occurs normally in GDF5-deficient mice

PubMed Central

Maier, Jennifer A.; Harfe, Brian D.

2011-01-01

Study Design The transition of the mouse embryonic notochord into nuclei pulposi was determined (“fate mapped”) in vivo in GDF-5 null mice using the Shhcre and R26R alleles. Objective To determine if abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5 null mice. Summary of Background Data The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5 null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5 null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or resulted from progressive postnatal degeneration of nuclei pulposi. Methods Gdf-5 mRNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5 null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24 week old mice. Results Our Gdf-5 mRNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate mapping experiments revealed that notochord cells in Gdf-5 null mice correctly form nuclei pulposi. Conclusion Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5 null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects. PMID:21278629
Fractalkine Signaling Regulates Macrophage Recruitment into the Cochlea and Promotes the Survival of Spiral Ganglion Neurons after Selective Hair Cell Lesion.

PubMed

Kaur, Tejbeer; Zamani, Darius; Tong, Ling; Rubel, Edwin W; Ohlemiller, Kevin K; Hirose, Keiko; Warchol, Mark E

2015-11-11

Macrophages are recruited into the cochlea in response to injury caused by acoustic trauma or ototoxicity, but the nature of the interaction between macrophages and the sensory structures of the inner ear remains unclear. The present study examined the role of fractalkine signaling in regulating the injury-evoked behavior of macrophages following the selective ablation of cochlear hair cells. We used a novel transgenic mouse model in which the human diphtheria toxin receptor (huDTR) is selectively expressed under the control of Pou4f3, a hair cell-specific transcription factor. Administration of diphtheria toxin (DT) to these mice resulted in nearly complete ablation of cochlear hair cells, with no evident pathology among supporting cells, spiral ganglion neurons, or cells of the cochlear lateral wall. Hair cell death led to an increase in macrophages associated with the sensory epithelium of the cochlea. Their numbers peaked at 14 days after DT and then declined at later survival times. Increased macrophages were also observed within the spiral ganglion, but their numbers remained elevated for (at least) 56 d after DT. To investigate the role of fractalkine signaling in macrophage recruitment, we crossed huDTR mice to a mouse line that lacks expression of the fractalkine receptor (CX3CR1). Disruption of fractalkine signaling reduced macrophage recruitment into both the sensory epithelium and spiral ganglion and also resulted in diminished survival of spiral ganglion neurons after hair cell death. Our results suggest a fractalkine-mediated interaction between macrophages and the neurons of the cochlea. It is known that damage to the inner ear leads to recruitment of inflammatory cells (macrophages), but the chemical signals that initiate this recruitment and the functions of macrophages in the damaged ear are unclear. Here we show that fractalkine signaling regulates macrophage recruitment into the cochlea and also promotes the survival of cochlear afferents after selective hair cell lesion. Because these afferent neurons carry sound information from the cochlea to the auditory brainstem, their survival is a key determinant of the success of cochlear prosthetics. Our data suggest that fractalkine signaling in the cochlea is neuroprotective, and reveal a previously uncharacterized interaction between cells of the cochlea and the innate immune system. Copyright © 2015 the authors 0270-6474/15/3515050-12$15.00/0.
Two-Dimensional Cochlear Micromechanics Measured In Vivo Demonstrate Radial Tuning within the Mouse Organ of Corti

PubMed Central

Lee, Hee Yoon; Raphael, Patrick D.; Xia, Anping; Kim, Jinkyung; Grillet, Nicolas; Applegate, Brian E.; Ellerbee Bowden, Audrey K.

2016-01-01

The exquisite sensitivity and frequency discrimination of mammalian hearing underlie the ability to understand complex speech in noise. This requires force generation by cochlear outer hair cells (OHCs) to amplify the basilar membrane traveling wave; however, it is unclear how amplification is achieved with sharp frequency tuning. Here we investigated the origin of tuning by measuring sound-induced 2-D vibrations within the mouse organ of Corti in vivo. Our goal was to determine the transfer function relating the radial shear between the structures that deflect the OHC bundle, the tectorial membrane and reticular lamina, to the transverse motion of the basilar membrane. We found that, after normalizing their responses to the vibration of the basilar membrane, the radial vibrations of the tectorial membrane and reticular lamina were tuned. The radial tuning peaked at a higher frequency than transverse basilar membrane tuning in the passive, postmortem condition. The radial tuning was similar in dead mice, indicating that this reflected passive, not active, mechanics. These findings were exaggerated in TectaC1509G/C1509G mice, where the tectorial membrane is detached from OHC stereocilia, arguing that the tuning of radial vibrations within the hair cell epithelium is distinct from tectorial membrane tuning. Together, these results reveal a passive, frequency-dependent contribution to cochlear filtering that is independent of basilar membrane filtering. These data argue that passive mechanics within the organ of Corti sharpen frequency selectivity by defining which OHCs enhance the vibration of the basilar membrane, thereby tuning the gain of cochlear amplification. SIGNIFICANCE STATEMENT Outer hair cells amplify the traveling wave within the mammalian cochlea. The resultant gain and frequency sharpening are necessary for speech discrimination, particularly in the presence of background noise. Here we measured the 2-D motion of the organ of Corti in mice and found that the structures that stimulate the outer hair cell stereocilia, the tectorial membrane and reticular lamina, were sharply tuned in the radial direction. Radial tuning was similar in dead mice and in mice lacking a tectorial membrane. This suggests that radial tuning comes from passive mechanics within the hair cell epithelium, and that these mechanics, at least in part, may tune the gain of cochlear amplification. PMID:27488636
International Neural Network Society Annual Meeting (1994) Held in San Diego, California on 5-9 June 1994. Volume 3.

DTIC Science & Technology

1994-06-09

Competitive Neural Nets Speed Complex Fluid Flow Calculations 1-366 T. Long, E. Hanzevack Neural Networks for Steam Boiler MIMO Modeling and Advisory Control...Gallinr The Cochlear Nucleus and Primary Cortex as a Sequence of Distributed Neural Filters in Phoneme IV-607 Perception J. Antrobus, C. Tarshish, S...propulsion linear model, a fuel flow actuator modelled as a linear second order system with position and rate limits, and a thrust vectoring actuator
Results using the OPAL strategy in Mandarin speaking cochlear implant recipients.

PubMed

Vandali, Andrew E; Dawson, Pam W; Arora, Komal

2017-01-01

To evaluate the effectiveness of an experimental pitch-coding strategy for improving recognition of Mandarin lexical tone in cochlear implant (CI) recipients. Adult CI recipients were tested on recognition of Mandarin tones in quiet and speech-shaped noise at a signal-to-noise ratio of +10 dB; Mandarin sentence speech-reception threshold (SRT) in speech-shaped noise; and pitch discrimination of synthetic complex-harmonic tones in quiet. Two versions of the experimental strategy were examined: (OPAL) linear (1:1) mapping of fundamental frequency (F0) to the coded modulation rate; and (OPAL+) transposed mapping of high F0s to a lower coded rate. Outcomes were compared to results using the clinical ACE™ strategy. Five Mandarin speaking users of Nucleus® cochlear implants. A small but significant benefit in recognition of lexical tones was observed using OPAL compared to ACE in noise, but not in quiet, and not for OPAL+ compared to ACE or OPAL in quiet or noise. Sentence SRTs were significantly better using OPAL+ and comparable using OPAL to those using ACE. No differences in pitch discrimination thresholds were observed across strategies. OPAL can provide benefits to Mandarin lexical tone recognition in moderately noisy conditions and preserve perception of Mandarin sentences in challenging noise conditions.

LOSS OF SESTRIN 2 POTENTIATES THE EARLY ONSET OF AGE-RELATED SENSORY CELL DEGENERATION IN THE COCHLEA

PubMed Central

ZHANG, CELIA; SUN, WEI; LI, JI; XIONG, BINBIN; FRYE, MITCHELL D.; DING, DALIAN; SALVI, RICHARD; KIM, MI-JUNG; SOMEYA, SHINICHI; HU, BO HUA

2017-01-01

Sestrin 2 (SESN2) is a stress-inducible protein that protects tissues from oxidative stress and delays the aging process. However, its role in maintaining the functional and structural integrity of the cochlea is largely unknown. Here, we report the expression of SESN2 protein in the sensory epithelium, particularly in hair cells. Using C57BL/6J mice, a mouse model of age-related cochlear degeneration, we observed a significant age-related reduction in SESN2 expression in cochlear tissues that was associated with early onset hearing loss and accelerated age-related sensory cell degeneration that progressed from the base toward the apex of the cochlea. Hair cell death occurred by caspase-8 mediated apoptosis. Compared to C57BL/6J control mice, Sesn2 KO mice displayed enhanced expression of proinflammatory genes and activation of basilar membrane macrophages, suggesting that loss of SESN2 function provokes the immune response. Together, these results suggest that Sesn2 plays an important role in cochlear homeostasis and immune responses to stress. PMID:28818524
Effects of Electrical Stimulation Rate on Speech Recognition in Cochlear Implant Users

PubMed Central

Park, Sung Hye; Kim, Eunoak; Lee, Hyo-Jeong

2012-01-01

Background and Objectives The stimulus signals delivered in cochlear implant (CI) systems are generally derived by sampling the temporal envelope of each channel at some constant rate and using its intensity to control the stimulation current level delivered to the corresponding electrode site. The objective of the study was to investigate speech recognition performance of cochlear implant users in quiet and noisy environments using either moderate or high rates of electrical stimulations. Materials and Methods Six post-lingually deafened adult users of the Nucleus CI24 cochlear implant (Contour® electrode array, Cochlear™, Macquarie Park, Australia) with the Freedom® speech processor participated in the study. Stimulation rates of 900 and 2400 pulses-per-second/channel (pps/ch) were used after both stimulation programs were balanced for loudness. Monosyllabic word and sentence recognition scores in quiet and noisy environments were evaluated for each stimulation program after two months of practice. Subjects were also asked to respond to a questionnaire to examine their preference to any stimulation rate in different hearing conditions. Results Word recognition scores for monosyllabic words in quiet conditions with the 900 stimulation rate was better than that of the 2400 stimulation rate, although no significant differences between them were found for sentence test in noise. A survey questionnaire indicated that most subjects preferred the 900 stimulation rate to the 2400 stimulation rate, especially in quiet conditions. Conclusions Most subjects indicated a preference for 900 pps/ch rate in quiet conditions. It is recommended to remap at 900 pps/ch for those CI users whose performance in quiet conditions is less than ideal. PMID:24653862
Effects of electrical stimulation rate on speech recognition in cochlear implant users.

PubMed

Park, Sung Hye; Kim, Eunoak; Lee, Hyo-Jeong; Kim, Hyung-Jong

2012-04-01

The stimulus signals delivered in cochlear implant (CI) systems are generally derived by sampling the temporal envelope of each channel at some constant rate and using its intensity to control the stimulation current level delivered to the corresponding electrode site. The objective of the study was to investigate speech recognition performance of cochlear implant users in quiet and noisy environments using either moderate or high rates of electrical stimulations. Six post-lingually deafened adult users of the Nucleus CI24 cochlear implant (Contour® electrode array, Cochlear™, Macquarie Park, Australia) with the Freedom® speech processor participated in the study. Stimulation rates of 900 and 2400 pulses-per-second/channel (pps/ch) were used after both stimulation programs were balanced for loudness. Monosyllabic word and sentence recognition scores in quiet and noisy environments were evaluated for each stimulation program after two months of practice. Subjects were also asked to respond to a questionnaire to examine their preference to any stimulation rate in different hearing conditions. Word recognition scores for monosyllabic words in quiet conditions with the 900 stimulation rate was better than that of the 2400 stimulation rate, although no significant differences between them were found for sentence test in noise. A survey questionnaire indicated that most subjects preferred the 900 stimulation rate to the 2400 stimulation rate, especially in quiet conditions. Most subjects indicated a preference for 900 pps/ch rate in quiet conditions. It is recommended to remap at 900 pps/ch for those CI users whose performance in quiet conditions is less than ideal.
Recognition of Speech from the Television with Use of a Wireless Technology Designed for Cochlear Implants.

PubMed

Duke, Mila Morais; Wolfe, Jace; Schafer, Erin

2016-05-01

Cochlear implant (CI) recipients often experience difficulty understanding speech in noise and speech that originates from a distance. Many CI recipients also experience difficulty understanding speech originating from a television. Use of hearing assistance technology (HAT) may improve speech recognition in noise and for signals that originate from more than a few feet from the listener; however, there are no published studies evaluating the potential benefits of a wireless HAT designed to deliver audio signals from a television directly to a CI sound processor. The objective of this study was to compare speech recognition in quiet and in noise of CI recipients with the use of their CI alone and with the use of their CI and a wireless HAT (Cochlear Wireless TV Streamer). A two-way repeated measures design was used to evaluate performance differences obtained in quiet and in competing noise (65 dBA) with the CI sound processor alone and with the sound processor coupled to the Cochlear Wireless TV Streamer. Sixteen users of Cochlear Nucleus 24 Freedom, CI512, and CI422 implants were included in the study. Participants were evaluated in four conditions including use of the sound processor alone and use of the sound processor with the wireless streamer in quiet and in the presence of competing noise at 65 dBA. Speech recognition was evaluated in each condition with two full lists of Computer-Assisted Speech Perception Testing and Training Sentence-Level Test sentences presented from a light-emitting diode television. Speech recognition in noise was significantly better with use of the wireless streamer compared to participants' performance with their CI sound processor alone. There was also a nonsignificant trend toward better performance in quiet with use of the TV Streamer. Performance was significantly poorer when evaluated in noise compared to performance in quiet when the TV Streamer was not used. Use of the Cochlear Wireless TV Streamer designed to stream audio from a television directly to a CI sound processor provides better speech recognition in quiet and in noise when compared to performance obtained with use of the CI sound processor alone. American Academy of Audiology.
Isolation of sphere-forming stem cells from the mouse inner ear.

PubMed

Oshima, Kazuo; Senn, Pascal; Heller, Stefan

2009-01-01

The mammalian inner ear has very limited ability to regenerate lost sensory hair cells. This deficiency becomes apparent when hair cell loss leads to hearing loss as a result of either ototoxic insult or the aging process. Coincidently, with this inability to regenerate lost hair cells, the adult cochlea does not appear to harbor cells with a proliferative capacity that could serve as progenitor cells for lost cells. In contrast, adult mammalian vestibular sensory epithelia display a limited ability for hair cell regeneration, and sphere-forming cells with stem cell features can be isolated from the adult murine vestibular system. The neonatal inner ear, however, does harbor sphere-forming stem cells residing in cochlear and vestibular tissues. Here, we provide protocols to isolate sphere-forming stem cells from neonatal vestibular and cochlear sensory epithelia as well as from the spiral ganglion. We further describe procedures for sphere propagation, cell differentiation, and characterization of inner ear cell types derived from spheres. Sphere-forming stem cells from the mouse inner ear are an important tool for the development of cellular replacement strategies of damaged inner ears and are a bona fide progenitor cell source for transplantation studies.
Characterization of neuronal cell death in the spiral ganglia of a mouse model of endolymphatic hydrops.

PubMed

Semaan, Maroun T; Zheng, Qing Y; Han, Fengchan; Zheng, Yuxi; Yu, Heping; Heaphy, John C; Megerian, Cliff A

2013-04-01

Spiral ganglion neurons (SGN) in the Phex male mouse, a murine model of postnatal endolymphatic hydrops (ELH) undergo progressive deterioration reminiscent of human and other animal models of ELH with features suggesting apoptosis as an important mechanism. Histologic analysis of the mutant's cochlea demonstrates ELH by postnatal Day (P) 21 and SGN loss by P90. The SGN loss seems to occur in a consistent topographic pattern beginning at the cochlear apex. SGN were counted at P60, P90, and P120. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative PCR, and immunohistochemical analyses of activated caspase-3, caspase-8, and caspase-9 were performed on cochlear sections obtained from mutants and controls. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay (TUNEL) was carried out on 2 mutants and 2 controls. Corrected SGN counts in control mice were greater in the apical turn of the cochleae at P90 and P120, respectively (p < 0.01). Increased expression of activated caspase-3, caspase-8, and caspase-9 was seen in the mutant. At later time points, activated caspase expression gradually declined in the apical turns and increased in basal turns of the cochlea. Quantitative and semiquantitative PCR analysis confirmed increased expression of caspase-3, caspase-8, and caspase-9 at P21 and P40. TUNEL staining demonstrated apoptosis at P90 in the apical and basal turns of the mutant cochleae. SGN degeneration in the Phex /Y mouse seems to mimic patterns observed in other animals with ELH. Apoptosis plays an important role in the degeneration of the SGN in the Phex male mouse.
Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice.

PubMed

Garcia-Pino, Elisabet; Gessele, Nikodemus; Koch, Ursula

2017-08-02

Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS ( Fmr1 KO ), we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. Fmr1 KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences. Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry, auditory processing was also affected in adult Fmr1 KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area, and a shift in the interaural level difference function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS. SIGNIFICANCE STATEMENT Fragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social interactions, contributing to their isolation. Here, a mouse model of FXS was used to investigate the auditory brainstem where basic sound information is first processed. Loss of the Fragile X mental retardation protein leads to excessive excitatory compared with inhibitory inputs in neurons extracting information about sound levels. Functionally, this elevated excitation results in increased firing rates, and abnormal coding of frequency and binaural sound localization cues. Imbalanced early-stage sound level processing could partially explain the auditory processing deficits in FXS. Copyright © 2017 the authors 0270-6474/17/377403-17$15.00/0.
Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

PubMed

Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

2014-04-01

The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.
Communication outcomes for groups of children using cochlear implants enrolled in auditory-verbal, aural-oral, and bilingual-bicultural early intervention programs.

PubMed

Dettman, Shani; Wall, Elizabeth; Constantinescu, Gabriella; Dowell, Richard

2013-04-01

The relative impact of early intervention approach on speech perception and language skills was examined in these 3 well-matched groups of children using cochlear implants. Eight children from an auditory verbal intervention program were identified. From a pediatric database, researchers blind to the outcome data, identified 23 children from auditory oral programs and 8 children from bilingual-bicultural programs with the same inclusion criteria and equivalent demographic factors. All child participants were male, had congenital profound hearing loss (pure tone average >80 dBHL), no additional disabilities, were within the normal IQ range, were monolingual English speakers, had no unusual findings on computed tomography/magnetic resonance imaging, and received hearing aids and cochlear implants at a similar age and before 4 years of age. Open-set speech perception (consonant-nucleus-consonant [CNC] words and Bamford-Kowal-Bench [BKB] sentences) and the Peabody Picture Vocabulary Test (PPVT) were administered. The mean age at cochlear implant was 1.7 years (range, 0.8-3.9; SD, 0.7), mean test age was 5.4 years (range, 2.5-10.1; SD, 1.7), and mean device experience was 3.7 years (range, 0.7-7.9; SD, 1.8). Results indicate mean CNC scores of 60%, 43%, and 24% and BKB scores of 77%, 77%, and 56% for the auditory-verbal (AV), aural-oral (AO), and bilingual-bicultural (BB) groups, respectively. The mean PPVT delay was 13, 19, and 26 months for AV, AO, and BB groups, respectively. Despite equivalent child demographic characteristics at the outset of this study, by 3 years postimplant, there were significant differences in AV, AO, and BB groups. Results support consistent emphasis on oral/aural input to achieve optimum spoken communication outcomes for children using cochlear implants.
Bidirectional Telemetry Controller for Neuroprosthetic Devices

PubMed Central

Sharma, Vishnu; McCreery, Douglas B.; Han, Martin; Pikov, Victor

2010-01-01

We present versatile multifunctional programmable controller with bidirectional data telemetry, implemented using existing commercial microchips and standard Bluetooth protocol, which adds convenience, reliability, and ease-of-use to neuroprosthetic devices. Controller, weighing 190 g, is placed on animal's back and provides bidirectional sustained telemetry rate of 500 kb/s, allowing real-time control of stimulation parameters and viewing of acquired data. In continuously-active state, controller consumes ∼420 mW and operates without recharge for 8 h. It features independent 16-channel current-controlled stimulation, allowing current steering; customizable stimulus current waveforms; recording of stimulus voltage waveforms and evoked neuronal responses with stimulus artifact blanking circuitry. Flexibility, scalability, cost-efficiency, and a user-friendly computer interface of this device allow use in animal testing for variety of neuroprosthetic applications. Initial testing of the controller has been done in a feline model of brainstem auditory prosthesis. In this model, the electrical stimulation is applied to the array of microelectrodes implanted in the ventral cochlear nucleus, while the evoked neuronal activity was recorded with the electrode implanted in the contralateral inferior colliculus. Stimulus voltage waveforms to monitor the access impedance of the electrodes were acquired at the rate of 312 kilosamples/s. Evoked neuronal activity in the inferior colliculus was recorded after the blanking (transient silencing) of the recording amplifier during the stimulus pulse, allowing the detection of neuronal responses within 100 μs after the end of the stimulus pulse applied in the cochlear nucleus. PMID:19933010
Emergence of band-pass filtering through adaptive spiking in the owl's cochlear nucleus

PubMed Central

MacLeod, Katrina M.; Lubejko, Susan T.; Steinberg, Louisa J.; Köppl, Christine; Peña, Jose L.

2014-01-01

In the visual, auditory, and electrosensory modalities, stimuli are defined by first- and second-order attributes. The fast time-pressure signal of a sound, a first-order attribute, is important, for instance, in sound localization and pitch perception, while its slow amplitude-modulated envelope, a second-order attribute, can be used for sound recognition. Ascending the auditory pathway from ear to midbrain, neurons increasingly show a preference for the envelope and are most sensitive to particular envelope modulation frequencies, a tuning considered important for encoding sound identity. The level at which this tuning property emerges along the pathway varies across species, and the mechanism of how this occurs is a matter of debate. In this paper, we target the transition between auditory nerve fibers and the cochlear nucleus angularis (NA). While the owl's auditory nerve fibers simultaneously encode the fast and slow attributes of a sound, one synapse further, NA neurons encode the envelope more efficiently than the auditory nerve. Using in vivo and in vitro electrophysiology and computational analysis, we show that a single-cell mechanism inducing spike threshold adaptation can explain the difference in neural filtering between the two areas. We show that spike threshold adaptation can explain the increased selectivity to modulation frequency, as input level increases in NA. These results demonstrate that a spike generation nonlinearity can modulate the tuning to second-order stimulus features, without invoking network or synaptic mechanisms. PMID:24790170
The precerebellar linear nucleus in the mouse defined by connections, immunohistochemistry, and gene expression.

PubMed

Fu, YuHong; Tvrdik, Petr; Makki, Nadja; Palombi, Olivier; Machold, Robert; Paxinos, George; Watson, Charles

2009-05-19

The linear nucleus (Li) is a prominent cell group in the caudal hindbrain, which was first described in a study of cerebellar afferents in the rat by [Watson, C.R.R., Switzer, R.C. III, 1978. Trigeminal projections to cerebellar tactile areas in the rat origin mainly from N. interpolaris and N. principalis. Neurosci. Lett. 10, 77-82.]. It was named for its elongated appearance in transverse sections. Since this original description in the rat, reference to the nucleus seems to have been largely absent from experimental studies of mammalian precerebellar nuclei. We therefore set out to define the cytoarchitecture, cerebellar connections, and molecular characteristics of Li in the mouse. In coronal Nissl sections at the level of the rostral inferior olive, it consists of two parallel bands of cells joined at their dorsal apex by a further band of cells, making the shape of the Greek capital letter pi. Our three-dimensional reconstruction demonstrated that the nucleus is continuous with the lateral reticular nucleus (LRt) and that the ambiguus nucleus sits inside the arch of Li. Cerebellar horseradish peroxidase injections confirmed that the cells of Li project to cerebellum. We have shown that Li cells express Atoh1 and Wnt1 lineage markers that are known to label the rhombic lip derived precerebellar nuclei. We have examined the relationship of Li cells to a number of molecular markers, and have found that many of the cells express a nonphosphorylated epitope in neurofilament H (SMI 32), a feature they share with the LRt. The mouse Li therefore appears to be a rostrodorsal extension of the LRt.
GABA Immunoreactivity in Auditory and Song Control Brain Areas of Zebra Finches

PubMed Central

Pinaud, Raphael; Mello, Claudio V.

2009-01-01

Inhibitory transmission is critical to sensory and motor processing and is believed to play a role in experience-dependent plasticity. The main inhibitory neurotransmitter in vertebrates, GABA, has been implicated in both sensory and motor aspects of vocalization in songbirds. To understand the role of GABAergic mechanisms in vocal communication, GABAergic elements must be characterized fully. Hence, we investigated GABA immunohistochemistry in the zebra finch brain, emphasizing auditory areas and song control nuclei. Several nuclei of the ascending auditory pathway showed a moderate to high density of GABAergic neurons including the cochlear nuclei, nucleus laminaris, superior olivary nucleus, mesencephalic nucleus lateralis pars dorsalis, and nucleus ovoidalis. Telencephalic auditory areas, including field L subfields L1, L2a and L3, as well as the caudomedial nidopallium (NCM) and mesopallium (CMM), contained GABAergic cells at particularly high densities. Considerable GABA labeling was also seen in the shelf area of caudodorsal nidopallium, and the cup area in the arcopallium, as well as in area X, the lateral magnocellular nucleus of the anterior nidopallium, the robust nucleus of the arcopallium and nidopallial nucleus HVC. GABAergic cells were typically small, most likely local inhibitory interneurons, although large GABA-positive cells that were sparsely distributed were also identified. GABA-positive neurites and puncta were identified in most nuclei of the ascending auditory pathway and in song control nuclei. Our data are in accordance with a prominent role of GABAergic mechanisms in regulating the neural circuits involved in song perceptual processing, motor production, and vocal learning in songbirds. PMID:17466487
Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea

PubMed Central

Chen, Yan; Lu, Xiaoling; Guo, Luo; Ni, Wenli; Zhang, Yanping; Zhao, Liping; Wu, Lingjie; Sun, Shan; Zhang, Shasha; Tang, Mingliang; Li, Wenyan; Chai, Renjie; Li, Huawei

2017-01-01

Hair cell (HC) loss is the major cause of permanent sensorineural hearing loss in mammals. Unlike lower vertebrates, mammalian cochlear HCs cannot regenerate spontaneously after damage, although the vestibular system does maintain limited HC regeneration capacity. Thus HC regeneration from the damaged sensory epithelium has been one of the main areas of research in the field of hearing restoration. Hedgehog signaling plays important roles during the embryonic development of the inner ear, and it is involved in progenitor cell proliferation and differentiation as well as the cell fate decision. In this study, we show that recombinant Sonic Hedgehog (Shh) protein effectively promotes sphere formation, proliferation, and differentiation of Lgr5+ progenitor cells isolated from the neonatal mouse cochlea. To further explore this, we determined the effect of Hedgehog signaling on cell proliferation and HC regeneration in cultured cochlear explant from transgenic R26-SmoM2 mice that constitutively activate Hedgehog signaling in the supporting cells of the cochlea. Without neomycin treatment, up-regulation of Hedgehog signaling did not significantly promote cell proliferation or new HC formation. However, after injury to the sensory epithelium by neomycin treatment, the over-activation of Hedgehog signaling led to significant supporting cell proliferation and HC regeneration in the cochlear epithelium explants. RNA sequencing and real-time PCR were used to compare the transcripts of the cochleae from control mice and R26-SmoM2 mice, and multiple genes involved in the proliferation and differentiation processes were identified. This study has important implications for the treatment of sensorineural hearing loss by manipulating the Hedgehog signaling pathway. PMID:29311816
Deletion of PDZD7 disrupts the Usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice.

PubMed

Zou, Junhuang; Zheng, Tihua; Ren, Chongyu; Askew, Charles; Liu, Xiao-Ping; Pan, Bifeng; Holt, Jeffrey R; Wang, Yong; Yang, Jun

2014-05-01

Usher syndrome type 2 (USH2) is the predominant form of USH, a leading genetic cause of combined deafness and blindness. PDZD7, a paralog of two USH causative genes, USH1C and USH2D (WHRN), was recently reported to be implicated in USH2 and non-syndromic deafness. It encodes a protein with multiple PDZ domains. To understand the biological function of PDZD7 and the pathogenic mechanism caused by PDZD7 mutations, we generated and thoroughly characterized a Pdzd7 knockout mouse model. The Pdzd7 knockout mice exhibit congenital profound deafness, as assessed by auditory brainstem response, distortion product otoacoustic emission and cochlear microphonics tests, and normal vestibular function, as assessed by their behaviors. Lack of PDZD7 leads to the disorganization of stereocilia bundles and a reduction in mechanotransduction currents and sensitivity in cochlear outer hair cells. At the molecular level, PDZD7 determines the localization of the USH2 protein complex, composed of USH2A, GPR98 and WHRN, to ankle links in developing cochlear hair cells, likely through its direct interactions with these three proteins. The localization of PDZD7 to the ankle links of cochlear hair bundles also relies on USH2 proteins. In photoreceptors of Pdzd7 knockout mice, the three USH2 proteins largely remain unchanged at the periciliary membrane complex. The electroretinogram responses of both rod and cone photoreceptors are normal in knockout mice at 1 month of age. Therefore, although the organization of the USH2 complex appears different in photoreceptors, it is clear that PDZD7 plays an essential role in organizing the USH2 complex at ankle links in developing cochlear hair cells. GenBank accession numbers: KF041446, KF041447, KF041448, KF041449, KF041450, KF041451.
Subcollicular projections to the auditory thalamus and collateral projections to the inferior colliculus.

PubMed

Schofield, Brett R; Mellott, Jeffrey G; Motts, Susan D

2014-01-01

Experiments in several species have identified direct projections to the medial geniculate nucleus (MG) from cells in subcollicular auditory nuclei. Moreover, many cochlear nucleus cells that project to the MG send collateral projections to the inferior colliculus (IC) (Schofield et al., 2014). We conducted three experiments to characterize projections to the MG from the superior olivary and the lateral lemniscal regions in guinea pigs. For experiment 1, we made large injections of retrograde tracer into the MG. Labeled cells were most numerous in the superior paraolivary nucleus, ventral nucleus of the trapezoid body, lateral superior olivary nucleus, ventral nucleus of the lateral lemniscus, ventrolateral tegmental nucleus, paralemniscal region and sagulum. Additional sources include other periolivary nuclei and the medial superior olivary nucleus. The projections are bilateral with an ipsilateral dominance (66%). For experiment 2, we injected tracer into individual MG subdivisions. The results show that the subcollicular projections terminate primarily in the medial MG, with the dorsal MG a secondary target. The variety of projecting nuclei suggest a range of functions, including monaural and binaural aspects of hearing. These direct projections could provide the thalamus with some of the earliest (i.e., fastest) information regarding acoustic stimuli. For experiment 3, we made large injections of different retrograde tracers into one MG and the homolateral IC to identify cells that project to both targets. Such cells were numerous and distributed across many of the nuclei listed above, mostly ipsilateral to the injections. The prominence of the collateral projections suggests that the same information is delivered to both the IC and the MG, or perhaps that a common signal is being delivered as a preparatory indicator or temporal reference point. The results are discussed from functional and evolutionary perspectives.
Subcollicular projections to the auditory thalamus and collateral projections to the inferior colliculus

PubMed Central

Schofield, Brett R.; Mellott, Jeffrey G.; Motts, Susan D.

2014-01-01

Experiments in several species have identified direct projections to the medial geniculate nucleus (MG) from cells in subcollicular auditory nuclei. Moreover, many cochlear nucleus cells that project to the MG send collateral projections to the inferior colliculus (IC) (Schofield et al., 2014). We conducted three experiments to characterize projections to the MG from the superior olivary and the lateral lemniscal regions in guinea pigs. For experiment 1, we made large injections of retrograde tracer into the MG. Labeled cells were most numerous in the superior paraolivary nucleus, ventral nucleus of the trapezoid body, lateral superior olivary nucleus, ventral nucleus of the lateral lemniscus, ventrolateral tegmental nucleus, paralemniscal region and sagulum. Additional sources include other periolivary nuclei and the medial superior olivary nucleus. The projections are bilateral with an ipsilateral dominance (66%). For experiment 2, we injected tracer into individual MG subdivisions. The results show that the subcollicular projections terminate primarily in the medial MG, with the dorsal MG a secondary target. The variety of projecting nuclei suggest a range of functions, including monaural and binaural aspects of hearing. These direct projections could provide the thalamus with some of the earliest (i.e., fastest) information regarding acoustic stimuli. For experiment 3, we made large injections of different retrograde tracers into one MG and the homolateral IC to identify cells that project to both targets. Such cells were numerous and distributed across many of the nuclei listed above, mostly ipsilateral to the injections. The prominence of the collateral projections suggests that the same information is delivered to both the IC and the MG, or perhaps that a common signal is being delivered as a preparatory indicator or temporal reference point. The results are discussed from functional and evolutionary perspectives. PMID:25100950
Surgical implications of perimodiolar cochlear implant electrode design: avoiding intracochlear damage and scala vestibuli insertion.

PubMed

Briggs, R J; Tykocinski, M; Saunders, E; Hellier, W; Dahm, M; Pyman, B; Clark, G M

2001-09-01

To review the mechanisms and nature of intracochlear damage associated with cochlear implant electrode array insertion, in particular, the various perimodiolar electrode designs. Make recommendations regarding surgical techniques for the Nucleus Contour electrode to ensure correct position and minimal insertion trauma. The potential advantages of increased modiolar proximity of intracochlear multichannel electrode arrays are a reduction in stimulation thresholds, an increase in dynamic range and more localized neural excitation. This may improve speech perception and reduce power consumption. These advantages may be negated if increased intracochlear damage results from the method used to position the electrodes close to the modiolus. A review of the University of Melbourne Department of Otolaryngology experience with temporal bone safety studies using the Nucleus standard straight electrode array and a variety of perimodiolar electrode array designs; comparison with temporal bone insertion studies from other centres and postmortem histopathology studies reported in the literature. Review of our initial clinical experience using the Nucleus Contour electrode array. The nature of intracochlear damage resulting from electrode insertion trauma ranges from minor, localized, spiral ligament tear to diffuse organ of Corti disruption and osseous spiral lamina fracture. The type of damage depends on the mechanical characteristics of the electrode array, the stiffness, curvature and size of the electrode in relation to the scala, and the surgical technique. The narrow, flexible, straight arrays are the least traumatic. Pre-curved or stiffer arrays are associated with an incidence of basilar membrane perforation. The cochleostomy must be correctly sited in relation to the round window to ensure scala tympani insertion. A cochleostomy anterior to the round window rather than inferior may lead to scala media or scala vestibuli insertion. Proximity of electrodes to the modiolus can be achieved without intracochlear damage provided the electrode array is a free fit within the scala, of appropriate size and shape, and accurate scala tympani insertion is performed.
Murine intracochlear drug delivery: reducing concentration gradients within the cochlea.

PubMed

Borkholder, David A; Zhu, Xiaoxia; Hyatt, Brad T; Archilla, Alfredo S; Livingston, William J; Frisina, Robert D

2010-09-01

Direct delivery of compounds to the mammalian inner ear is most commonly achieved by absorption or direct injection through the round window membrane (RWM), or infusion through a basal turn cochleostomy. These methods provide direct access to cochlear structures, but with a strong basal-to-apical concentration gradient consistent with a diffusion-driven distribution. This gradient limits the efficacy of therapeutic approaches for apical structures, and puts constraints on practical therapeutic dose ranges. A surgical approach involving both a basal turn cochleostomy and a posterior semicircular canal canalostomy provides opportunities for facilitated perfusion of cochlear structures to reduce concentration gradients. Infusion of fixed volumes of artificial perilymph (AP) and sodium salicylate were used to evaluate two surgical approaches in the mouse: cochleostomy-only (CO), or cochleostomy-plus-canalostomy (C+C). Cochlear function was evaluated via closed-system distortion product otoacoustic emissions (DPOAE) threshold level measurements from 8 to 49 kHz. AP infusion confirmed no surgical impact to auditory function, while shifts in DPOAE thresholds were measured during infusion of salicylate and AP (washout). Frequency dependent shifts were compared for the CO and C+C approaches. Computer simulations modeling diffusion, volume flow, interscala transport, and clearance mechanisms provided estimates of drug concentration as a function of cochlear position. Simulated concentration profiles were compared to frequency-dependent shifts in measured auditory responses using a cochlear tonotopic map. The impact of flow rate on frequency dependent DPOAE threshold shifts was also evaluated for both surgical approaches. Both the C+C approach and a flow rate increase were found to provide enhanced response for lower frequencies, with evidence suggesting the C+C approach reduces concentration gradients within the cochlea. Copyright (c) 2010 Elsevier B.V. All rights reserved.
Murine Intracochlear Drug Delivery: Reducing Concentration Gradients within the Cochlea

PubMed Central

Borkholder, David A.; Zhu, Xiaoxia; Hyatt, Brad T.; Archilla, Alfredo S.; Livingston, William J.; Frisina, Robert D.

2010-01-01

Direct delivery of compounds to the mammalian inner ear is most commonly achieved by absorption or direct injection through the round window membrane (RWM), or infusion through a basal turn cochleostomy. These methods provide direct access to cochlear structures, but with a strong basal-to-apical concentration gradient consistent with a diffusion-driven distribution. This gradient limits the efficacy of therapeutic approaches for apical structures, and puts constraints on practical therapeutic dose ranges. A surgical approach involving both a basal turn cochleostomy and a posterior semicircular canal canalostomy provides opportunities for facilitated perfusion of cochlear structures to reduce concentration gradients. Infusion of fixed volumes of artificial perilymph (AP) and sodium salicylate were used to evaluate two surgical approaches in the mouse: cochleostomy-only (CO), or cochleostomy-plus-canalostomy (C+C). Cochlear function was evaluated via closed-system distortion product otoacoustic emissions (DPOAE) threshold level measurements from 8-49 kHz. AP infusion confirmed no surgical impact to auditory function, while shifts in DPOAE thresholds were measured during infusion of salicylate and AP (washout). Frequency dependent shifts were compared for the CO and C+C approaches. Computer simulations modeling diffusion, volume flow, interscala transport, and clearance mechanisms provided estimates of drug concentration as a function of cochlear position. Simulated concentration profiles were compared to frequency-dependent shifts in measured auditory responses using a cochlear tonotopic map. The impact of flow rate on frequency dependent DPOAE threshold shifts was also evaluated for both surgical approaches. Both the C+C approach and a flow rate increase were found to provide enhanced response for lower frequencies, with evidence suggesting the C+C approach reduces concentration gradients within the cochlea. PMID:20451593

A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall.

PubMed

Mei, Ling; Chen, Jin; Zong, Liang; Zhu, Yan; Liang, Chun; Jones, Raleigh O; Zhao, Hong-Bo

2017-12-01

Digenic Connexin26 (Cx26, GJB2) and Cx30 (GJB6) heterozygous mutations are the second most frequent cause of recessive deafness in humans. However, the underlying deafness mechanism remains unclear. In this study, we created different double Cx26 and Cx30 heterozygous (Cx26 +/- /Cx30 +/- ) mouse models to investigate the underlying pathological changes and deafness mechanism. We found that double Cx26 +/- /Cx30 +/- heterozygous mice had hearing loss. Endocochlear potential (EP), which is a driving force for hair cells producing auditory receptor current, was reduced. However, unlike Cx26 homozygous knockout (Cx26 -/- ) mice, the cochlea in Cx26 +/- /Cx30 +/- mice displayed normal development and had no apparent hair cell degeneration. Gap junctions (GJs) in the cochlea form two independent networks: the epithelial cell GJ network in the organ of Corti and the connective tissue GJ network in the cochlear lateral wall. We further found that double heterozygous deletion of Cx26 and Cx30 in the epithelial cells did not reduce EP and had normal hearing, suggesting that Cx26 +/- /Cx30 +/- may mainly impair gap junctional functions in the cochlear lateral wall and lead to EP reduction and hearing loss. Most of Cx26 and Cx30 in the cochlear lateral wall co-expressed in the same gap junctional plaques. Moreover, sole Cx26 +/- or Cx30 +/- heterozygous mice had no hearing loss. These data further suggest that digenic Cx26 and Cx30 mutations may impair heterozygous coupling of Cx26 and Cx30 in the cochlear lateral wall to reduce EP, thereby leading to hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.
Hearing-in-Noise Benefits After Bilateral Simultaneous Cochlear Implantation Continue to Improve 4 Years After Implantation

PubMed Central

Eapen, Rose J.; Buss, Emily; Adunka, Marcia Clark; Pillsbury, Harold C.; Buchman, Craig A.

2012-01-01

Objective The purpose of this 4-year longitudinal study was to assess the stability of the binaural benefits of head shadow, summation, and squelch for bilateral cochlear implant recipients and to quantify these benefits for the understanding of speech in noise. Design This is a prospective study of 9 patients who received simultaneous bilateral insertion of MED-EL COMBI +40 cochlear implants in a single-stage operation at the University of North Carolina, Chapel Hill, NC. Each patient had postlingual deafness of short duration before insertion of the device. Each year, the patients were tested for word recognition using consonant-nucleus-consonant words in quiet and speech perception in noise using City University of New York sentences. These tests were administered using direct audio input to the implants. Head-related transfer functions were used to simulate speech in noise testing in a spatial environment. Speech was always presented at midline (0), and the noise masker was presented at either side or midline (−90, 0, +90 degrees). Results The binaural benefits of head shadow and summation effects developed early in the postoperative period and remained stable throughout the follow-up period. Squelch developed more slowly and was first demonstrated at 12 months after implantation but continued to increase beyond the first year of follow-up. Conclusion Benefits of head shadow and summation emerge early and remain stable. However, squelch has the most protracted period of development, with increasing benefit after a year or more of implant experience. These data support the idea that binaural integration continues several years after insertion of bilateral cochlear implant devices. PMID:19180675
Spontaneous Discharge Patterns in Cochlear Spiral Ganglion Cells Prior to the Onset of Hearing in Cats

PubMed Central

Jones, Timothy A.; Leake, Patricia A.; Snyder, Russell L.; Stakhovskaya, Olga; Bonham, Ben

2008-01-01

Spontaneous neural activity has been recorded in the auditory nerve of cats as early as 2 days postnatal (P2 ), yet individual auditory neurons do not respond to ambient sound levels below 90–100 dB SPL until about P10. Significant refinement of the central projections from the spiral ganglion to the cochlear nucleus occurs during this neonatal period. This refinement may be dependent on peripheral spontaneous discharge activity. We recorded from single spiral ganglion cells in kittens aged P3 to P9. The spiral ganglion was accessed via the round window through the spiral lamina. A total of 112 ganglion cells were isolated for study in 9 animals. Spike rates in neonates were very low, ranging from 0.06 to 56 sp/s with a mean of 3.09 +/− 8.24 sp/s. Ganglion cells in neonatal kittens exhibited remarkable repetitive spontaneous bursting discharge patterns. The unusual patterns were evident in the large mean interval coefficient of variation (CVi = 2.9 +/−1.6) and burst index of 5.2 +/− 3.5 across ganglion cells. Spontaneous bursting patterns in these neonatal mammals were similar to those reported for cochlear ganglion cells of the embryonic chicken suggesting this may be a general phenomenon that is common across animal classes. Rhythmic spontaneous discharge of retinal ganglion cells has been shown to be important in the development of central retinotopic projections and normal binocular vision (Shatz, 1996, Proc Natl Acad Sci 93). Bursting rhythms in cochlear ganglion cells may play a similar role in the auditory system during pre-hearing periods. PMID:17686914
A circuit for detection of interaural time differences in the nucleus laminaris of turtles.

PubMed

Willis, Katie L; Carr, Catherine E

2017-11-15

The physiological hearing range of turtles is approximately 50-1000 Hz, as determined by cochlear microphonics ( Wever and Vernon, 1956a). These low frequencies can constrain sound localization, particularly in red-eared slider turtles, which are freshwater turtles with small heads and isolated middle ears. To determine if these turtles were sensitive to interaural time differences (ITDs), we investigated the connections and physiology of their auditory brainstem nuclei. Tract tracing experiments showed that cranial nerve VIII bifurcated to terminate in the first-order nucleus magnocellularis (NM) and nucleus angularis (NA), and the NM projected bilaterally to the nucleus laminaris (NL). As the NL received inputs from each side, we developed an isolated head preparation to examine responses to binaural auditory stimulation. Magnocellularis and laminaris units responded to frequencies from 100 to 600 Hz, and phase-locked reliably to the auditory stimulus. Responses from the NL were binaural, and sensitive to ITD. Measures of characteristic delay revealed best ITDs around ±200 μs, and NL neurons typically had characteristic phases close to 0, consistent with binaural excitation. Thus, turtles encode ITDs within their physiological range, and their auditory brainstem nuclei have similar connections and cell types to other reptiles. © 2017. Published by The Company of Biologists Ltd.
Matrix Metalloproteinase Dysregulation in the Stria Vascularis of Mice with Alport Syndrome

PubMed Central

Gratton, Michael Anne; Rao, Velidi H.; Meehan, Daniel T.; Askew, Charles; Cosgrove, Dominic

2005-01-01

Alport syndrome results from mutations in genes encoding collagen α3(IV), α4(IV), or α5(IV) and is characterized by progressive glomerular disease associated with a high-frequency sensorineural hearing loss. Earlier studies of a gene knockout mouse model for Alport syndrome noted thickening of strial capillary basement membranes in the cochlea, suggesting that the stria vascularis is the primary site of cochlear pathogenesis. Here we combine a novel cochlear microdissection technique with molecular analyses to illustrate significant quantitative alterations in strial expression of mRNAs encoding matrix metalloproteinases-2, -9, -12, and -14. Gelatin zymography of extracts from the stria vascularis confirmed these findings. Treatment of Alport mice with a small molecule inhibitor of these matrix metalloproteinases exacerbated strial capillary basement membrane thickening, demonstrating that alterations in basement membrane metabolism result in matrix accumulation in the strial capillary basement membranes. This is the first demonstration of true quantitative analysis of specific mRNAs for matrix metalloproteinases in a cochlear microcompartment. Further, these data suggest that the altered basement membrane composition in Alport stria influences the expression of genes involved in basement membrane metabolism. PMID:15855646
[Thalamus and Attention].

PubMed

Tokoro, Kazuhiko; Sato, Hironobu; Yamamoto, Mayumi; Nagai, Yoshiko

2015-12-01

Attention is the process by which information and selection occurs, the thalamus plays an important role in the selective attention of visual and auditory information. Selective attention is a conscious effort; however, it occurs subconsciously, as well. The lateral geniculate body (LGB) filters visual information before it reaches the cortex (bottom-up attention). The thalamic reticular nucleus (TRN) provides a strong inhibitory input to both the LGB and pulvinar. This regulation involves focusing a spotlight on important information, as well as inhibiting unnecessary background information. Behavioral contexts more strongly modulate activity of the TRN and pulvinar influencing feedforward and feedback information transmission between the frontal, temporal, parietal and occipital cortical areas (top-down attention). The medial geniculate body (MGB) filters auditory information the TRN inhibits the MGB. Attentional modulation occurring in the auditory pathway among the cochlea, cochlear nucleus, superior olivary complex, and inferior colliculus is more important than that of the MGB and TRN. We also discuss the attentional consequence of thalamic hemorrhage.
Evaluation of speech reception threshold in noise in young Cochlear™ Nucleus® system 6 implant recipients using two different digital remote microphone technologies and a speech enhancement sound processing algorithm.

PubMed

Razza, Sergio; Zaccone, Monica; Meli, Aannalisa; Cristofari, Eliana

2017-12-01

Children affected by hearing loss can experience difficulties in challenging and noisy environments even when deafness is corrected by Cochlear implant (CI) devices. These patients have a selective attention deficit in multiple listening conditions. At present, the most effective ways to improve the performance of speech recognition in noise consists of providing CI processors with noise reduction algorithms and of providing patients with bilateral CIs. The aim of this study was to compare speech performances in noise, across increasing noise levels, in CI recipients using two kinds of wireless remote-microphone radio systems that use digital radio frequency transmission: the Roger Inspiro accessory and the Cochlear Wireless Mini Microphone accessory. Eleven Nucleus Cochlear CP910 CI young user subjects were studied. The signal/noise ratio, at a speech reception threshold (SRT) value of 50%, was measured in different conditions for each patient: with CI only, with the Roger or with the MiniMic accessory. The effect of the application of the SNR-noise reduction algorithm in each of these conditions was also assessed. The tests were performed with the subject positioned in front of the main speaker, at a distance of 2.5 m. Another two speakers were positioned at 3.50 m. The main speaker at 65 dB issued disyllabic words. Babble noise signal was delivered through the other speakers, with variable intensity. The use of both wireless remote microphones improved the SRT results. Both systems improved gain of speech performances. The gain was higher with the Mini Mic system (SRT = -4.76) than the Roger system (SRT = -3.01). The addition of the NR algorithm did not statistically further improve the results. There is significant improvement in speech recognition results with both wireless digital remote microphone accessories, in particular with the Mini Mic system when used with the CP910 processor. The use of a remote microphone accessory surpasses the benefit of application of NR algorithm. Copyright © 2017. Published by Elsevier B.V.
Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.

PubMed

McCann, Matthew R; Tamplin, Owen J; Rossant, Janet; Séguin, Cheryle A

2012-01-01

Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.
Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development

PubMed Central

McCann, Matthew R.; Tamplin, Owen J.; Rossant, Janet; Séguin, Cheryle A.

2012-01-01

SUMMARY Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration. PMID:22028328
Neurons identified by NeuN/Fox-3 immunoreactivity have a novel distribution in the hamster and mouse suprachiasmatic nucleus.

PubMed

Morin, Lawrence P; Hefton, Sara; Studholme, Keith M

2011-11-03

The suprachiasmatic nucleus (SCN) has several structural characteristics and cell phenotypes shared across species. Here, we describe a novel feature of SCN anatomy that is seen in both hamster and mouse. Frozen sections through the SCN were obtained from fixed brains and stained for the presence of immunoreactivity to neuronal nuclear protein (NeuN-IR) using a mouse monoclonal antibody which is known to exclusively identify neurons. NeuN-IR did not identify all SCN neurons as medial NeuN-IR neurons were generally not present. In the hamster, NeuN-IR cells are present rostrally, scattered in the dorsal half of the nucleus. More caudally, the NeuN-IR cells are largely, but not exclusively, scattered inside the lateral and dorsolateral border. At mid- to mid-caudal SCN levels, a dense group of NeuN-IR cells extends from the dorsolateral border ventromedially to encompass the central subnucleus of the SCN (SCNce). The pattern is similar in the mouse SCN. NeuN-IR does not co-localize with either cholecystokinin- or vasoactive intestinal polypeptide, but does with vasopressin-IR in the caudal SCN. In the hamster SCNce, numerous cells contain both calbindin- and NeuN-IR. The distribution of NeuN-IR cells in the SCN is unique, especially with regard to its generally lateral location through the length of the nucleus. The distribution of NeuN-IR cells is not consistent with most schemas representing SCN organization or with terminology referring to its widely accepted subdivisions. NeuN has recently been identified as Fox-3 protein. Its function in the SCN is not known, nor is it known why a large proportion of SCN cells do not contain NeuN-IR. Copyright © 2011 Elsevier B.V. All rights reserved.
Connections of the Auditory Brainstem in a Songbird, Taeniopygia guttata. II. Projections of Nucleus Angularis and Nucleus Laminaris to the Superior Olive and Lateral Lemniscal Nuclei

PubMed Central

Krützfeldt, Nils O.E.; Logerot, Priscilla; Kubke, M. Fabiana; Wild, J. Martin

2013-01-01

Three nuclei of the lateral lemniscus are present in the zebra finch, ventral (LLV), intermediate (LLI), and dorsal (LLD). LLV is separate from the superior olive (OS): it lies closer to the spinal lemniscus and extends much further rostrally around the pontine periphery. LLI extends from a caudal position ventrolateral to the principal sensory trigeminal nucleus (LLIc) to a rostral position medial to the ventrolateral parabrachial nucleus (LLIr). LLD consists of posterior (LLDp) and anterior (LLDa) parts, which are largely coextensive rostrocaudally, although LLDa lies medial to LLDp. All nuclei are identifiable on the basis of cytochrome oxidase activity. The cochlear nucleus angularis (NA) and the third-order nucleus laminaris (NL) project on OS predominantly ipsilaterally, on LLV and LLI predominantly contralaterally, and on LLD contralaterally only. The NA projections are heavier than those of NL and differ from them primarily in their terminations within LLD: NA projects to LLDp, whereas NL projects to LLDa. In this the projections are similar to those in the barn owl (Takahashi and Konishi [1988] J Comp Neurol 274:212–238), in which time and intensity pathways remain separate as far as the central nucleus of the inferior colliculus (MLd). In contrast, in the zebra finch, although NA and NL projections remain separate within LLD, the projections of LLDa and LLDp become intermixed within MLd (Wild et al., J Comp Neurol, this issue), consistent with the intermixing of the direct NA and NL projections to MLd (Krützfeldt et al., J Comp Neurol, this issue). J. Comp. Neurol. 518:2135–2148, 2010. PMID:20394062
The Cytoarchitecture of the Inferior Colliculus Revisited

PubMed Central

Loftus, William C.; Malmierca, Manuel S.; Bishop, Deborah C.; Oliver, Douglas L.

2008-01-01

The inferior colliculus (IC) is the major component of the auditory midbrain and contains three major subdivisions: a central nucleus, a dorsal cortex, and a lateral cortex (LC). Discrepancies in the nomenclature and parcellation of the LC in the rat and cat seem to imply different, species-specific functions for this region. To establish a comparable parcellation of the LC for both rat and cat, we investigated the histochemistry and inputs of the LC. In both species, the deep lateral cortex is marked by a transition between the NADPH-d rich superficial cortex and a cytochrome oxidase rich central nucleus. In both species, focal injections of anterograde tracers in the cochlear nucleus at sites of known best frequency produced bands of labeled inputs in two different subdivisions of the IC. A medial band of axons terminated in the central nucleus, while shorter bands were located laterally and oriented nearly perpendicularly to the medial bands. In the rat, these lateral bands were located in the third, deepest layer of the lateral (external) cortex. In the cat, the bands were located in a region that was previously ascribed to the central nucleus, but now considered to belong to the third, deepest layer of the LC, the ventrolateral nucleus. In both species, the LC inputs had a tonotopic organization. In view of this parallel organization, we propose a common parcellation of the IC for rat and cat with a new nomenclature. The deep layer of the LC, previously referred to as layer 3 in the rat, is designated as the ‘ventrolateral nucleus’ of the LC, making it clear that this region is thought to be homologous with the ventrolateral nucleus in the cat. The similar organization of the LC implies that this subdivision of the IC has similar functions in cats and rats. PMID:18313229
Different pools of glutamate receptors mediate sensitivity to ambient glutamate in the cochlear nucleus

PubMed Central

Yang, Yang

2015-01-01

Ambient glutamate plays an important role in pathological conditions, such as stroke, but its role during normal activity is not clear. In addition, it is not clear how ambient glutamate acts on glutamate receptors with varying affinities or subcellular localizations. To address this, we studied “endbulb of Held” synapses, which are formed by auditory nerve fibers onto bushy cells (BCs) in the anteroventral cochlear nucleus. When ambient glutamate was increased by applying the glutamate reuptake inhibitor TFB-TBOA, BCs depolarized as a result of activation of N-methyl-d-aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs). Application of antagonists against NMDARs (in 0 Mg2+) or mGluRs caused hyperpolarization, indicating that these receptors were bound by a tonic source of glutamate. AMPA receptors did not show these effects, consistent with their lower glutamate affinity. We also evaluated the subcellular localization of the receptors activated by ambient glutamate. The mGluRs were not activated by synaptic stimulation and thus appear to be exclusively extrasynaptic. By contrast, NMDARs in both synaptic and extrasynaptic compartments were activated by ambient glutamate, as shown using the use-dependent antagonist MK-801. Levels of ambient glutamate appeared to be regulated in a spike-independent manner, and glia likely play a major role. These low levels of ambient glutamate likely have functional consequences, as even low concentrations of TBOA caused significant increases in BC spiking following synaptic stimulation. These results indicate that normal resting potential appears to be poised in the region of maximal sensitivity to small changes in ambient glutamate. PMID:25855696
Inhibitors of oxidative and hydrolytic endocannabinoid degradation do not enhance depolarization-induced suppression of excitation on dorsal cochlear nucleus glycinergic neurons.

PubMed

Zugaib, João; Leão, Ricardo M

2017-04-01

Neurons from the dorsal cochlear nucleus (DCN) present endocannabinoid (EC) dependent short-term synaptic plasticity in the form of depolarization-induced suppression of excitation (DSE). Postsynaptic calcium influx promotes EC synthesis and depression of neurotransmission. ECs can be degraded by a hydrolytic and an oxidative pathway, the latter via the enzyme cyclooxygenase 2 (COX-2). Hyperactivity in the DCN is related to the development of tinnitus, which can be induced by high doses of salicylate, a COX-2 inhibitor. Since EC-dependent plasticity in the DCN can affect its excitation-inhibition balance, we investigated the impact of inhibitors of both oxidative and hydrolytic EC metabolism on the DSE from the synapses between the parallel fibers and cartwheel neurons (PF-CW) in the DCN. We found that inhibitors of COX-2 (ibuprofen and indomethacin) did not alter DSE at the PF-CW synapse. Salicylate also did not alter DSE. However, we found that inhibitors of the hydrolytic pathway did not affect DSE magnitude, but surprisingly speeded DSE decay. We conclude that oxidative EC degradation in the PF-CW synapse is not relevant for termination of DSE and are probably not important for controlling this form of synaptic plasticity in the DCN PF-CW synapse. The lack of effect on DSE of high doses of salicylate also suggests that it is not acting by increasing DSE in the PF-CWC synapse. However, the counter intuitive effect of the hydrolytic inhibitors shows that increasing EC on this synapse have more complex effects on DSE. © 2016 Wiley Periodicals, Inc.
Interaction of the Mouse Polyomavirus Capsid Proteins with Importins Is Required for Efficient Import of Viral DNA into the Cell Nucleus.

PubMed

Soldatova, Irina; Prilepskaja, Terezie; Abrahamyan, Levon; Forstová, Jitka; Huérfano, Sandra

2018-03-31

The mechanism used by mouse polyomavirus (MPyV) overcomes the crowded cytosol to reach the nucleus has not been fully elucidated. Here, we investigated the involvement of importin α/β1 mediated transport in the delivery of MPyV genomes into the nucleus. Interactions of the virus with importin β1 were studied by co-immunoprecipitation and proximity ligation assay. For infectivity and nucleus delivery assays, the virus and its capsid proteins mutated in the nuclear localization signals (NLSs) were prepared and produced. We found that at early times post infection, virions bound importin β1 in a time dependent manner with a peak of interactions at 6 h post infection. Mutation analysis revealed that only when the NLSs of both VP1 and VP2/3 were disrupted, virus did not bind efficiently to importin β1 and its infectivity remarkably decreased (by 80%). Nuclear targeting of capsid proteins was improved when VP1 and VP2 were co-expressed. VP1 and VP2 were effectively delivered into the nucleus, even when one of the NLS, either VP1 or VP2, was disrupted. Altogether, our results showed that MPyV virions can use VP1 and/or VP2/VP3 NLSs in concert or individually to bind importins to deliver their genomes into the cell nucleus.
Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

PubMed Central

Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K.; Boon, Wah Chin

2014-01-01

Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females. PMID:24646567
Energy flow in passive and active 3D cochlear model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yanli; Steele, Charles; Puria, Sunil

Energy flow in the cochlea is an important characteristic of the cochlear traveling wave, and many investigators, such as von Békésy and Lighthill, have discussed this phenomenon. Particularly after the discovery of the motility of the outer hair cells (OHCs), the nature of the power gain of the cochlea has been a fundamental research question. In the present work, direct three-dimensional (3D) calculations of the power on cross sections of the cochlea and on the basilar membrane are performed based on a box model of the mouse cochlea. The distributions of the fluid pressure and fluid velocity in the scalamore » vestibuli are presented. The power output from the OHCs and the power loss due to fluid viscous damping are calculated along the length of the cochlea. This work provides a basis for theoretical calculations of the power gain of the OHCs from mechanical considerations.« less
Energy flow in passive and active 3D cochlear model

NASA Astrophysics Data System (ADS)

Wang, Yanli; Puria, Sunil; Steele, Charles

2015-12-01

Energy flow in the cochlea is an important characteristic of the cochlear traveling wave, and many investigators, such as von Békésy and Lighthill, have discussed this phenomenon. Particularly after the discovery of the motility of the outer hair cells (OHCs), the nature of the power gain of the cochlea has been a fundamental research question. In the present work, direct three-dimensional (3D) calculations of the power on cross sections of the cochlea and on the basilar membrane are performed based on a box model of the mouse cochlea. The distributions of the fluid pressure and fluid velocity in the scala vestibuli are presented. The power output from the OHCs and the power loss due to fluid viscous damping are calculated along the length of the cochlea. This work provides a basis for theoretical calculations of the power gain of the OHCs from mechanical considerations.
Nanoscale live cell imaging using hopping probe ion conductance microscopy

PubMed Central

Novak, Pavel; Li, Chao; Shevchuk, Andrew I.; Stepanyan, Ruben; Caldwell, Matthew; Hughes, Simon; Smart, Trevor G.; Gorelik, Julia; Ostanin, Victor P.; Lab, Max J.; Moss, Guy W. J.; Frolenkov, Gregory I.; Klenerman, David; Korchev, Yuri E.

2009-01-01

We describe a major advance in scanning ion conductance microscopy: a new hopping mode that allows non-contact imaging of the complex surfaces of live cells with resolution better than 20 nm. The effectiveness of this novel technique was demonstrated by imaging networks of cultured rat hippocampal neurons and mechanosensory stereocilia of mouse cochlear hair cells. The technique allows studying nanoscale phenomena on the surface of live cells under physiological conditions. PMID:19252505
Teratogenic impact of dioxin-activated AHR in laboratory animals

EPA Science Inventory

AHR and ARNT are expressed in mouse and human palatal shelves and in the urinary tract of the mouse fetus. AHR expression, translocation to the nucleus, binding to DRE, and activation are required for mediation of TCDD-induction of CP and HN. Although the human palate requires a ...

Retinal projections in the short-tailed fruit bat, Carollia perspicillata, as studied using the axonal transport of cholera toxin B subunit: Comparison with mouse.

PubMed

Scalia, Frank; Rasweiler, John J; Danias, John

2015-08-15

To provide a modern description of the Chiropteran visual system, the subcortical retinal projections were studied in the short-tailed fruit bat, Carollia perspicillata, using the anterograde transport of eye-injected cholera toxin B subunit, supplemented by the silver-impregnation of anterograde degeneration following eye removal, and compared with the retinal projections of the mouse. The retinal projections were heavily labeled by the transported toxin in both species. Almost all components of the murine retinal projection are present in Carollia in varying degrees of prominence and laterality. The projections: to the superior colliculus, accessory optic nuclei, and nucleus of the optic tract are predominantly or exclusively contralateral; to the dorsal lateral geniculate nucleus and posterior pretectal nucleus are predominantly contralateral; to the ventral lateral geniculate nucleus, intergeniculate leaflet, and olivary pretectal nucleus have a substantial ipsilateral component; and to the suprachiasmatic nucleus are symmetrically bilateral. The retinal projection in Carollia is surprisingly reduced at the anterior end of the dorsal lateral geniculate and superior colliculus, suggestive of a paucity of the relevant ganglion cells in the ventrotemporal retina. In the superior colliculus, in which the superficial gray layer is very thin, the projection is patchy in places where the layer is locally absent. Except for a posteriorly located lateral terminal nucleus, the other accessory optic nuclei are diminutive in Carollia, as is the nucleus of the optic tract. In both species the cholera toxin labeled sparse groups of apparently terminating axons in numerous regions not listed above. A question of their significance is discussed. © 2015 Wiley Periodicals, Inc.
Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus.

PubMed

Stefanescu, Roxana A; Shore, Susan E

2017-03-01

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long-term synaptic plasticity. In the dorsal cochlear nucleus (DCN), in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with N -methyl-d-aspartate (NMDA) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian long-term potentiation to anti-Hebbian long-term depression. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus timing-dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. In the present study, we blocked mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induced a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shifted toward more excitatory changes in StTDP, whereas units with initial suppressive learning rules transitioned toward a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity, suggesting a central role in the maladaptive plasticity associated with tinnitus pathology. NEW & NOTEWORTHY This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the dorsal cochlear nucleus coupled with simultaneous recordings of neural activity to clarify the contribution of muscarinic acetylcholine receptors (mAChRs) to in vivo fusiform cell baseline activity and auditory-somatosensory plasticity. We have determined that blocking the mAChRs increases the synchronization of spiking activity across the fusiform cell population and induces a dominant pattern of inversion in their stimulus timing-dependent plasticity. These modifications are consistent with similar changes established in previous tinnitus studies, suggesting that mAChRs might have a critical contribution in mediating the maladaptive alterations associated with tinnitus pathology. Blocking mAChRs also resulted in decreased fusiform cell spontaneous firing rates, which is in contrast with their tinnitus hyperactivity, suggesting that changes in the interactions between the cholinergic and GABAergic systems might also be an underlying factor in tinnitus pathology. Copyright © 2017 the American Physiological Society.
Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation.

PubMed

Preissl, Sebastian; Fang, Rongxin; Huang, Hui; Zhao, Yuan; Raviram, Ramya; Gorkin, David U; Zhang, Yanxiao; Sos, Brandon C; Afzal, Veena; Dickel, Diane E; Kuan, Samantha; Visel, Axel; Pennacchio, Len A; Zhang, Kun; Ren, Bing

2018-03-01

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.
Zincergic innervation from the anterior olfactory nucleus to the olfactory bulb displays plastic responses after mitral cell loss.

PubMed

Airado, Carmen; Gómez, Carmela; Recio, Javier S; Baltanás, Fernando C; Weruaga, Eduardo; Alonso, José R

2008-12-01

Zinc ions are selectively accumulated in certain neurons (zinc-enriched neurons). The mouse olfactory bulb is richly innervated by zinc-enriched terminals. Here, the plasticity of the zincergic system was studied in the olfactory bulb of the Purkinje Cell Degeneration mutant mouse, an animal with specific postnatal neurodegeneration of the main projection neurons of the olfactory bulb. The analysis focused particularly on the anterior olfactory nucleus since most centrifugal afferents coming to the olfactory bulb arise from this structure. Zinc-enriched terminals in the olfactory bulb and zinc-enriched somata in the anterior olfactory nucleus were visualized after selenite injections. Immunohistochemistry against the vesicular zinc transporter was also carried out to confirm the distribution pattern of zinc-enriched terminals in the olfactory bulb. The mutant mice showed a clear reorganization of zincergic centrifugal projections from the anterior olfactory nucleus to the olfactory bulb. First, all zincergic contralateral neurons projecting to the olfactory bulb were absent in the mutant mice. Second, a significant increase in the number of stained somata was detected in the ipsilateral anterior olfactory nucleus. Since no noticeable changes were observed in the zinc-enriched terminals in the olfactory bulb, it is conceivable that mitral cell loss could induce a reorganization of zinc-enriched projections coming from the anterior olfactory nucleus, probably directed at balancing the global zincergic centrifugal modulation. These results show that zincergic anterior olfactory nucleus cells projecting to the olfactory bulb undergo plastic changes to adapt to the loss of mitral cells in the olfactory bulb of Purkinje Cell Degeneration mutant mice.
Cochlear implant characteristics and speech perception skills of adolescents with long-term device use.

PubMed

Davidson, Lisa S; Geers, Ann E; Brenner, Christine

2010-10-01

Updated cochlear implant technology and optimized fitting can have a substantial impact on speech perception. The effects of upgrades in processor technology and aided thresholds on word recognition at soft input levels and sentence recognition in noise were examined. We hypothesized that updated speech processors and lower aided thresholds would allow improved recognition of soft speech without compromising performance in noise. 109 teenagers who had used a Nucleus 22-cochlear implant since preschool were tested with their current speech processor(s) (101 unilateral and 8 bilateral): 13 used the Spectra, 22 the ESPrit 22, 61 the ESPrit 3G, and 13 the Freedom. The Lexical Neighborhood Test (LNT) was administered at 70 and 50 dB SPL and the Bamford Kowal Bench sentences were administered in quiet and in noise. Aided thresholds were obtained for frequency-modulated tones from 250 to 4,000 Hz. Results were analyzed using repeated measures analysis of variance. Aided thresholds for the Freedom/3G group were significantly lower (better) than the Spectra/Sprint group. LNT scores at 50 dB were significantly higher for the Freedom/3G group. No significant differences between the 2 groups were found for the LNT at 70 or sentences in quiet or noise. Adolescents using updated processors that allowed for aided detection thresholds of 30 dB HL or better performed the best at soft levels. The BKB in noise results suggest that greater access to soft speech does not compromise listening in noise.
Ototoxicity of paclitaxel in rat cochlear organotypic cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Yang; Center for Hearing and Deafness, University at Buffalo, NY 14214; Ding, Dalian

Paclitaxel (taxol) is a widely used antineoplastic drug employed alone or in combination to treat many forms of cancer. Paclitaxel blocks microtubule depolymerization thereby stabilizing microtubules and suppressing cell proliferation and other cellular processes. Previous reports indicate that paclitaxel can cause mild to moderate sensorineural hearing loss and some histopathologic changes in the mouse cochlea; however, damage to the neurons and the underlying cell death mechanisms are poorly understood. To evaluate the ototoxicity of paclitaxel in more detail, cochlear organotypic cultures from postnatal day 3 rats were treated with paclitaxel for 24 or 48 h with doses ranging from 1more » to 30 μM. No obvious histopathologies were observed after 24 h treatment with any of the paclitaxel doses employed, but with 48 h treatment, paclitaxel damaged cochlear hair cells in a dose-dependent manner and also damaged auditory nerve fibers and spiral ganglion neurons (SGN) near the base of the cochlea. TUNEL labeling was negative in the organ of Corti, but positive in SGN with karyorrhexis 48 h after 30 μM paclitaxel treatment. In addition, caspase-6, caspase-8 and caspase-9 labeling was present in SGN treated with 30 μM paclitaxel for 48 h. These results suggest that caspase-dependent apoptotic pathways are involved in paclitaxel-induced damage of SGN, but not hair cells in cochlea. - Highlights: • Paclitaxel was toxic to cochlear hair cells and spiral ganglion neurons. • Paclitaxel-induced spiral ganglion degeneration was apoptotic. • Paclitaxel activated caspase-6, -8 and -8 in spiral ganglion neurons.« less
Localization of the calcium channel subunits Cav1.2 (alpha1C) and Cav2.3 (alpha1E) in the mouse organ of Corti.

PubMed

Waka, N; Knipper, M; Engel, J

2003-10-01

Voltage-activated Ca2+ channels play an important role in synaptic transmission, signal processing and development. The immunohistochemical localization of Cav1.2 (alpha1C) and Cav2.3 (alpha1E) Ca2+ channels was studied in the developing and adult mouse organ of Corti using subunit-specific antibodies and fluorescent secondary antibodies with cochlear cryosections. Cav1.2 immunoreactivity has been detected from postnatal day 14 (P14) onwards at the synapses between cholinergic medial efferents and outer hair cells as revealed by co-staining with anti-synaptophysin and anti-choline acetyltransferase. Most likely the Cav1.2 immunoreactivity was located presynaptically at the site of contact of the efferent bouton with the outer hair cell which suggests a role for class C L-type Ca2+ channels in synaptic transmission of the medial efferent system. The localization of the second Ca2+ channel tested, Cav2.3, showed a pronounced change during cochlear development. From P2 until P10, Cav2.3 immunoreactivity was found in the outer spiral bundle followed by the inner spiral bundle, efferent endings and by medial efferent fibers. Around P14, Cav2.3 immunoreactivity disappeared from these structures and from P19 onwards it was observed in the basal poles of the outer hair cell membranes.
Different pools of glutamate receptors mediate sensitivity to ambient glutamate in the cochlear nucleus.

PubMed

Yang, Yang; Xu-Friedman, Matthew A

2015-06-01

Ambient glutamate plays an important role in pathological conditions, such as stroke, but its role during normal activity is not clear. In addition, it is not clear how ambient glutamate acts on glutamate receptors with varying affinities or subcellular localizations. To address this, we studied "endbulb of Held" synapses, which are formed by auditory nerve fibers onto bushy cells (BCs) in the anteroventral cochlear nucleus. When ambient glutamate was increased by applying the glutamate reuptake inhibitor TFB-TBOA, BCs depolarized as a result of activation of N-methyl-D-aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs). Application of antagonists against NMDARs (in 0 Mg(2+)) or mGluRs caused hyperpolarization, indicating that these receptors were bound by a tonic source of glutamate. AMPA receptors did not show these effects, consistent with their lower glutamate affinity. We also evaluated the subcellular localization of the receptors activated by ambient glutamate. The mGluRs were not activated by synaptic stimulation and thus appear to be exclusively extrasynaptic. By contrast, NMDARs in both synaptic and extrasynaptic compartments were activated by ambient glutamate, as shown using the use-dependent antagonist MK-801. Levels of ambient glutamate appeared to be regulated in a spike-independent manner, and glia likely play a major role. These low levels of ambient glutamate likely have functional consequences, as even low concentrations of TBOA caused significant increases in BC spiking following synaptic stimulation. These results indicate that normal resting potential appears to be poised in the region of maximal sensitivity to small changes in ambient glutamate. Copyright © 2015 the American Physiological Society.
Increased contralateral suppression of otoacoustic emissions indicates a hyperresponsive medial olivocochlear system in humans with tinnitus and hyperacusis

PubMed Central

Shera, Christopher A.; Melcher, Jennifer R.

2014-01-01

Atypical medial olivocochlear (MOC) feedback from brain stem to cochlea has been proposed to play a role in tinnitus, but even well-constructed tests of this idea have yielded inconsistent results. In the present study, it was hypothesized that low sound tolerance (mild to moderate hyperacusis), which can accompany tinnitus or occur on its own, might contribute to the inconsistency. Sound-level tolerance (SLT) was assessed in subjects (all men) with clinically normal or near-normal thresholds to form threshold-, age-, and sex-matched groups: 1) no tinnitus/high SLT, 2) no tinnitus/low SLT, 3) tinnitus/high SLT, and 4) tinnitus/low SLT. MOC function was measured from the ear canal as the change in magnitude of distortion-product otoacoustic emissions (DPOAE) elicited by broadband noise presented to the contralateral ear. The noise reduced DPOAE magnitude in all groups (“contralateral suppression”), but significantly more reduction occurred in groups with tinnitus and/or low SLT, indicating hyperresponsiveness of the MOC system compared with the group with no tinnitus/high SLT. The results suggest hyperresponsiveness of the interneurons of the MOC system residing in the cochlear nucleus and/or MOC neurons themselves. The present data, combined with previous human and animal data, indicate that neural pathways involving every major division of the cochlear nucleus manifest hyperactivity and/or hyperresponsiveness in tinnitus and/or low SLT. The overactivation may develop in each pathway separately. However, a more parsimonious hypothesis is that top-down neuromodulation is the driving force behind ubiquitous overactivation of the auditory brain stem and may correspond to attentional spotlighting on the auditory domain in tinnitus and hyperacusis. PMID:25231612
Suppression of noise-induced hyperactivity in the dorsal cochlear nucleus following application of the cholinergic agonist, carbachol

PubMed Central

Manzoor, N.F.; Chen, G.; Kaltenbach, J.A.

2013-01-01

Increased spontaneous firing (hyperactivity) is induced in fusiform cells of the dorsal cochlear nucleus (DCN) following intense sound exposure and is implicated as a possible neural correlate of noise-induced tinnitus. Previous studies have shown that in normal hearing animals, fusiform cell activity can be modulated by activation of parallel fibers, which represent the axons of granule cells. The modulation consists of a transient excitation followed by a more prolonged period of inhibition, presumably reflecting direct excitatory inputs to fusiform cells and an indirect inhibitory input to fusiform cells from the granule cell-cartwheel cell system. We hypothesized that since granule cells can be activated by cholinergic inputs, it might be possible to suppress tinnitus-related hyperactivity of fusiform cells using the cholinergic agonist, carbachol. To test this hypothesis, we recorded multiunit spontaneous activity in the fusiform soma layer (FSL) of the DCN in control and tone-exposed hamsters (10 kHz, 115 dB SPL, 4 h) before and after application of carbachol to the DCN surface. In both exposed and control animals, 100 µM carbachol had a transient excitatory effect on spontaneous activity followed by a rapid weakening of activity to near or below normal levels. In exposed animals, the weakening of activity was powerful enough to completely abolish the hyperactivity induced by intense sound exposure. This suppressive effect was partially reversed by application of atropine and was not associated with significant changes in neural best frequencies (BF) or BF thresholds. These findings demonstrate that noise-induced hyperactivity can be pharmacologically controlled and raise the possibility that attenuation of tinnitus may be achievable by using an agonist of the cholinergic system. PMID:23721928
Suppression of noise-induced hyperactivity in the dorsal cochlear nucleus following application of the cholinergic agonist, carbachol.

PubMed

Manzoor, N F; Chen, G; Kaltenbach, J A

2013-07-26

Increased spontaneous firing (hyperactivity) is induced in fusiform cells of the dorsal cochlear nucleus (DCN) following intense sound exposure and is implicated as a possible neural correlate of noise-induced tinnitus. Previous studies have shown that in normal hearing animals, fusiform cell activity can be modulated by activation of parallel fibers, which represent the axons of granule cells. The modulation consists of a transient excitation followed by a more prolonged period of inhibition, presumably reflecting direct excitatory inputs to fusiform cells and an indirect inhibitory input to fusiform cells from the granule cell-cartwheel cell system. We hypothesized that since granule cells can be activated by cholinergic inputs, it might be possible to suppress tinnitus-related hyperactivity of fusiform cells using the cholinergic agonist, carbachol. To test this hypothesis, we recorded multiunit spontaneous activity in the fusiform soma layer (FSL) of the DCN in control and tone-exposed hamsters (10 kHz, 115 dB SPL, 4h) before and after application of carbachol to the DCN surface. In both exposed and control animals, 100 μM carbachol had a transient excitatory effect on spontaneous activity followed by a rapid weakening of activity to near or below normal levels. In exposed animals, the weakening of activity was powerful enough to completely abolish the hyperactivity induced by intense sound exposure. This suppressive effect was partially reversed by application of atropine and was usually not associated with significant changes in neural best frequencies (BF) or BF thresholds. These findings demonstrate that noise-induced hyperactivity can be pharmacologically controlled and raise the possibility that attenuation of tinnitus may be achievable by using an agonist of the cholinergic system. Copyright © 2013 Elsevier B.V. All rights reserved.
Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohistochemical and in situ hybridization study.

PubMed

Hannibal, Jens

2002-11-25

In the present study the localization of pituitary adenylate cyclase-activating peptide (PACAP)-expressing cell bodies and PACAP projections were mapped in the adult rat brain and spinal cord by using immunohistochemistry and in situ hybridization histochemistry. A widespread occurrence of PACAP-containing cell bodies was found, with the greatest accumulation in several hypothalamic nuclei and in several brainstem nuclei, especially the habenular nuclei, the pontine nucleus, the lateral parabrachial nucleus (LPB), and the vagal complex. PACAP was also present in cell bodies in the olfactory areas, in neocortical areas, in the hippocampus, in the vestibulo- and cochlear nuclei, in cell bodies of the intermediolateral cell column of the spinal cord and in Purkinje cells of the cerebellum, in the subfornical organ, and in the organum vasculosum of the lamina terminalis. An intense accumulation of PACAP-immunoreactive (-IR) nerve fibers was observed throughout the hypothalamus, in the amydaloid and extended amygdaloid complex, in the anterior and paraventricular thalamic nuclei, in the intergeniculate leaflet, in the pretectum, and in several brainstem nuclei, such as the parabrachial nucleus, the sensory trigeminal nucleus, and the nucleus of the solitary tract. PACAP-IR nerve fibers were also found in the area postrema, the posterior pituitary and the choroid plexus, and the dorsal and ventral horn of the spinal cord. The widespread distribution of PACAP in the brain and spinal cord suggests that PACAP is involved in the control of many autonomic and sensory functions as well as higher cortical processes. Copyright 2002 Wiley-Liss, Inc.
Polysialic acid enters the cell nucleus attached to a fragment of the neural cell adhesion molecule NCAM to regulate the circadian rhythm in mouse brain.

PubMed

Westphal, Nina; Kleene, Ralf; Lutz, David; Theis, Thomas; Schachner, Melitta

2016-07-01

In the mammalian nervous system, the neural cell adhesion molecule NCAM is the major carrier of the glycan polymer polysialic acid (PSA) which confers important functions to NCAM's protein backbone. PSA attached to NCAM contributes not only to cell migration, neuritogenesis, synaptic plasticity, and behavior, but also to regulation of the circadian rhythm by yet unknown molecular mechanisms. Here, we show that a PSA-carrying transmembrane NCAM fragment enters the nucleus after stimulation of cultured neurons with surrogate NCAM ligands, a phenomenon that depends on the circadian rhythm. Enhanced nuclear import of the PSA-carrying NCAM fragment is associated with altered expression of clock-related genes, as shown by analysis of cultured neuronal cells deprived of PSA by specific enzymatic removal. In vivo, levels of nuclear PSA in different mouse brain regions depend on the circadian rhythm and clock-related gene expression in suprachiasmatic nucleus and cerebellum is affected by the presence of PSA-carrying NCAM in the cell nucleus. Our conceptually novel observations reveal that PSA attached to a transmembrane proteolytic NCAM fragment containing part of the extracellular domain enters the cell nucleus, where PSA-carrying NCAM contributes to the regulation of clock-related gene expression and of the circadian rhythm. Copyright © 2016 Elsevier Inc. All rights reserved.
Monopolar Detection Thresholds Predict Spatial Selectivity of Neural Excitation in Cochlear Implants: Implications for Speech Recognition

PubMed Central

2016-01-01

The objectives of the study were to (1) investigate the potential of using monopolar psychophysical detection thresholds for estimating spatial selectivity of neural excitation with cochlear implants and to (2) examine the effect of site removal on speech recognition based on the threshold measure. Detection thresholds were measured in Cochlear Nucleus® device users using monopolar stimulation for pulse trains that were of (a) low rate and long duration, (b) high rate and short duration, and (c) high rate and long duration. Spatial selectivity of neural excitation was estimated by a forward-masking paradigm, where the probe threshold elevation in the presence of a forward masker was measured as a function of masker-probe separation. The strength of the correlation between the monopolar thresholds and the slopes of the masking patterns systematically reduced as neural response of the threshold stimulus involved interpulse interactions (refractoriness and sub-threshold adaptation), and spike-rate adaptation. Detection threshold for the low-rate stimulus most strongly correlated with the spread of forward masking patterns and the correlation reduced for long and high rate pulse trains. The low-rate thresholds were then measured for all electrodes across the array for each subject. Subsequently, speech recognition was tested with experimental maps that deactivated five stimulation sites with the highest thresholds and five randomly chosen ones. Performance with deactivating the high-threshold sites was better than performance with the subjects’ clinical map used every day with all electrodes active, in both quiet and background noise. Performance with random deactivation was on average poorer than that with the clinical map but the difference was not significant. These results suggested that the monopolar low-rate thresholds are related to the spatial neural excitation patterns in cochlear implant users and can be used to select sites for more optimal speech recognition performance. PMID:27798658
A Non-canonical Reticular-Limbic Central Auditory Pathway via Medial Septum Contributes to Fear Conditioning.

PubMed

Zhang, Guang-Wei; Sun, Wen-Jian; Zingg, Brian; Shen, Li; He, Jufang; Xiong, Ying; Tao, Huizhong W; Zhang, Li I

2018-01-17

In the mammalian brain, auditory information is known to be processed along a central ascending pathway leading to auditory cortex (AC). Whether there exist any major pathways beyond this canonical auditory neuraxis remains unclear. In awake mice, we found that auditory responses in entorhinal cortex (EC) cannot be explained by a previously proposed relay from AC based on response properties. By combining anatomical tracing and optogenetic/pharmacological manipulations, we discovered that EC received auditory input primarily from the medial septum (MS), rather than AC. A previously uncharacterized auditory pathway was then revealed: it branched from the cochlear nucleus, and via caudal pontine reticular nucleus, pontine central gray, and MS, reached EC. Neurons along this non-canonical auditory pathway responded selectively to high-intensity broadband noise, but not pure tones. Disruption of the pathway resulted in an impairment of specifically noise-cued fear conditioning. This reticular-limbic pathway may thus function in processing aversive acoustic signals. Copyright © 2017 Elsevier Inc. All rights reserved.
Treating Combat Hearing Loss with Atoh1 Gene Therapy

DTIC Science & Technology

2015-06-01

Student Rende Gu, M.D., Staff Scientist Hongyuan Zhang, Research Technician 10 8. REPORTABLE OUTCOMES: Informatics : We have compiled two...cochlear development. Materials and Methods Experimental animals. Atoh1 / [Mouse Genome Informatics (MGI): Atoh1tm1Hzo], Atoh1A1GFP/A1GFP (MGI...pregnant females at E15.5, E16.5, or E17.5 by oral gavage. Tamoxifen and progesterone were dissolved to- gether in peanut oil , both at a concentration of 20
Gray-level co-occurrence matrix analysis of several cell types in mouse brain using resolution-enhanced photothermal microscopy

NASA Astrophysics Data System (ADS)

Kobayashi, Takayoshi; Sundaram, Durga; Nakata, Kazuaki; Tsurui, Hiromichi

2017-03-01

Qualifications of intracellular structure were performed for the first time using the gray-level co-occurrence matrix (GLCM) method for images of cells obtained by resolution-enhanced photothermal imaging. The GLCM method has been used to extract five parameters of texture features for five different types of cells in mouse brain; pyramidal neurons and glial cells in the basal nucleus (BGl), dentate gyrus granule cells, cerebellar Purkinje cells, and cerebellar granule cells. The parameters are correlation, contrast, angular second moment (ASM), inverse difference moment (IDM), and entropy for the images of cells of interest in a mouse brain. The parameters vary depending on the pixel distance taken in the analysis method. Based on the obtained results, we identified that the most suitable GLCM parameter is IDM for pyramidal neurons and BGI, granule cells in the dentate gyrus, Purkinje cells and granule cells in the cerebellum. It was also found that the ASM is the most appropriate for neurons in the basal nucleus.
Endogenous neuropeptide Y depresses the afferent signaling of gastric acid challenge to the mouse brainstem via neuropeptide Y type Y2 and Y4 receptors.

PubMed

Wultsch, T; Painsipp, E; Thoeringer, C K; Herzog, H; Sperk, G; Holzer, P

2005-01-01

Vagal afferents signal gastric acid challenge to the nucleus tractus solitarii of the rat brainstem. This study investigated whether nucleus tractus solitarii neurons in the mouse also respond to gastric acid challenge and whether this chemonociceptive input is modified by neuropeptide Y acting via neuropeptide Y receptors of type Y2 or Y4. The gastric mucosa of female mice was exposed to different concentrations of HCl or saline, excitation of neurons in the nucleus tractus solitarii visualized by c-Fos immunohistochemistry, gastric emptying deduced from the gastric volume recovery, and gastric lesion formation evaluated by planimetry. Relative to saline, intragastric HCl (0.15-0.35 M) increased the number of c-Fos-expressing cells in the nucleus tractus solitarii in a concentration-dependent manner, inhibited gastric emptying but failed to cause significant hemorrhagic injury in the stomach. Mice in which the Y2 or Y4 receptor gene had been deleted responded to gastric acid challenge with a significantly higher expression of c-Fos in the nucleus tractus solitarii, the increases amounting to 39 and 31%, respectively. The HCl-induced inhibition of gastric emptying was not altered by deletion of the Y2 or Y4 receptor gene. BIIE0246 ((S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)-oxodibenz[b,e] azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl] acetyl]-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamide; 0.03 mmol/kg s.c.), a Y2 receptor antagonist which does not cross the blood-brain barrier, did not modify the c-Fos response to gastric acid challenge. The Y2 receptor agonist peptide YY-(3-36) (0.1 mg/kg intraperitoneally) likewise failed to alter the gastric HCl-evoked expression of c-Fos in the nucleus tractus solitarii. BIIE0246, however, prevented the effect of peptide YY-(3-36) to inhibit gastric acid secretion as deduced from measurement of intragastric pH. The current data indicate that gastric challenge with acid concentrations that do not induce overt injury but inhibit gastric emptying is signaled to the mouse nucleus tractus solitarii. Endogenous neuropeptide Y acting via Y2 and Y4 receptors depresses the afferent input to the nucleus tractus solitarii by a presumably central site of action.
In vitro modifications of the scala tympani environment and the cochlear implant array surface.

PubMed

Kontorinis, Georgios; Scheper, Verena; Wissel, Kirsten; Stöver, Timo; Lenarz, Thomas; Paasche, Gerrit

2012-09-01

To investigate the influence of alterations of the scala tympani environment and modifications of the surface of cochlear implant electrode arrays on insertion forces in vitro. Research experimental study. Fibroblasts producing neurotrophic factors were cultivated on the surface of Nucleus 24 Contour Advance electrodes. Forces were recorded by an Instron 5542 Force Measurement System as three modified arrays were inserted into an artificial scala tympani model filled with phosphate-buffered saline (PBS). The recorded forces were compared to control groups including three unmodified electrodes inserted into a model filled with PBS (unmodified environment) or Healon (current practice). Fluorescence microscopy was used before and after the insertions to identify any remaining fibroblasts. Additionally, three Contour Advance electrodes were inserted into an artificial model, filled with alginate/barium chloride solution at different concentrations, while insertion forces were recorded. Modification of the scala tympani environment with 50% to 75% alginate gel resulted in a significant decrease in the insertion forces. The fibroblast-coated arrays also led to decreased forces comparable to those recorded with Healon. Fluorescence microscopy revealed fully cell-covered arrays before and partially covered arrays after the insertion; the fibroblasts on the arrays' modiolar surface remained intact. Modifications of the scala tympani's environment with 50% to 75% alginate/barium chloride and of the cochlear implant electrode surface with neurotrophic factor-producing fibroblasts drastically reduce the insertion forces. As both modifications may serve future intracochlear therapies, it is expected that these might additionally reduce possible insertion trauma. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
Determining electrically evoked compound action potential thresholds: a comparison of computer versus human analysis methods.

PubMed

Glassman, E Katelyn; Hughes, Michelle L

2013-01-01

Current cochlear implants (CIs) have telemetry capabilities for measuring the electrically evoked compound action potential (ECAP). Neural Response Telemetry (Cochlear) and Neural Response Imaging (Advanced Bionics [AB]) can measure ECAP responses across a range of stimulus levels to obtain an amplitude growth function. Software-specific algorithms automatically mark the leading negative peak, N1, and the following positive peak/plateau, P2, and apply linear regression to estimate ECAP threshold. Alternatively, clinicians may apply expert judgments to modify the peak markers placed by the software algorithms, or use visual detection to identify the lowest level yielding a measurable ECAP response. The goals of this study were to: (1) assess the variability between human and computer decisions for (a) marking N1 and P2 and (b) determining linear-regression threshold (LRT) and visual-detection threshold (VDT); and (2) compare LRT and VDT methods within and across human- and computer-decision methods. ECAP amplitude-growth functions were measured for three electrodes in each of 20 ears (10 Cochlear Nucleus® 24RE/CI512, and 10 AB CII/90K). LRT, defined as the current level yielding an ECAP with zero amplitude, was calculated for both computer- (C-LRT) and human-picked peaks (H-LRT). VDT, defined as the lowest level resulting in a measurable ECAP response, was also calculated for both computer- (C-VDT) and human-picked peaks (H-VDT). Because Neural Response Imaging assigns peak markers to all waveforms but does not include waveforms with amplitudes less than 20 μV in its regression calculation, C-VDT for AB subjects was defined as the lowest current level yielding an amplitude of 20 μV or more. Overall, there were significant correlations between human and computer decisions for peak-marker placement, LRT, and VDT for both manufacturers (r = 0.78-1.00, p < 0.001). For Cochlear devices, LRT and VDT correlated equally well for both computer- and human-picked peaks (r = 0.98-0.99, p < 0.001), which likely reflects the well-defined Neural Response Telemetry algorithm and the lower noise floor in the 24RE and CI512 devices. For AB devices, correlations between LRT and VDT for both peak-picker methods were weaker than for Cochlear devices (r = 0.69-0.85, p < 0.001), which likely reflect the higher noise floor of the system. Disagreement between computer and human decisions regarding the presence of an ECAP response occurred for 5 % of traces for Cochlear devices and 2.1 % of traces for AB devices. Results indicate that human and computer peak-picking methods can be used with similar accuracy for both Cochlear and AB devices. Either C-VDT or C-LRT can be used with equal confidence for Cochlear 24RE and CI512 recipients because both methods are strongly correlated with human decisions. However, for AB devices, greater variability exists between different threshold-determination methods. This finding should be considered in the context of using ECAP measures to assist with programming CIs.

The Peptide Near the C Terminus Regulates Receptor CAR Nuclear Translocation Induced by Xenochemicals in Mouse Liver

PubMed Central

Zelko, Igor; Sueyoshi, Tatsuya; Kawamoto, Takeshi; Moore, Rick; Negishi, Masahiko

2001-01-01

In response to phenobarbital (PB) and other PB-type inducers, the nuclear receptor CAR translocates to the mouse liver nucleus (T. Kawamoto et al., Mol. Cell. Biol. 19:6318–6322, 1999). To define the translocation mechanism, fluorescent protein-tagged human CAR (hCAR) was expressed in the mouse livers using the in situ DNA injection and gene delivery systems. As in the wild-type hCAR, the truncated receptor lacking the C-terminal 10 residues (i.e., AF2 domain) translocated to the nucleus, indicating that the PB-inducible translocation is AF2 independent. Deletion of the 30 C-terminal residues abolished the receptor translocation, and subsequent site-directed mutagenesis delineated the PB-inducible translocation activity of the receptor to the peptide L313GLL316AEL319. Ala mutations of Leu313, Leu316, or Leu319 abrogated the translocation of CAR in the livers, while those of Leu312 or Leu315 did not affect the nuclear translocation. The leucine-rich peptide dictates the nuclear translocation of hCAR in response to various PB-type inducers and appears to be conserved in the mouse and rat receptors. PMID:11283262
Hypoxia Induces a Metabolic Shift and Enhances the Stemness and Expansion of Cochlear Spiral Ganglion Stem/Progenitor Cells

PubMed Central

Chao, Ting-Ting; Sytwu, Huey-Kang; Li, Shiue-Li; Fang, Mei-Cho; Chen, Hang-Kang; Lin, Yi-Chun; Kuo, Chao-Yin

2015-01-01

Previously, we demonstrated that hypoxia (1% O2) enhances stemness markers and expands the cell numbers of cochlear stem/progenitor cells (SPCs). In this study, we further investigated the long-term effect of hypoxia on stemness and the bioenergetic status of cochlear spiral ganglion SPCs cultured at low oxygen tensions. Spiral ganglion SPCs were obtained from postnatal day 1 CBA/CaJ mouse pups. The measurement of oxygen consumption rate, extracellular acidification rate (ECAR), and intracellular adenosine triphosphate levels corresponding to 20% and 5% oxygen concentrations was determined using a Seahorse XF extracellular flux analyzer. After low oxygen tension cultivation for 21 days, the mean size of the hypoxia-expanded neurospheres was significantly increased at 5% O2; this correlated with high-level expression of hypoxia-inducible factor-1 alpha (Hif-1α), proliferating cell nuclear antigen (PCNA), cyclin D1, Abcg2, nestin, and Nanog proteins but downregulated expression of p27 compared to that in a normoxic condition. Low oxygen tension cultivation tended to increase the side population fraction, with a significant difference found at 5% O2 compared to that at 20% O2. In addition, hypoxia induced a metabolic energy shift of SPCs toward higher basal ECARs and higher maximum mitochondrial respiratory capacity but lower proton leak than under normoxia, where the SPC metabolism was switched toward glycolysis in long-term hypoxic cultivation. PMID:26236724
BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.

PubMed

Crispino, Giulia; Di Pasquale, Giovanni; Scimemi, Pietro; Rodriguez, Laura; Galindo Ramirez, Fabian; De Siati, Romolo Daniele; Santarelli, Rosa Maria; Arslan, Edoardo; Bortolozzi, Mario; Chiorini, John A; Mammano, Fabio

2011-01-01

The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans.
Low-resolution electromagnetic tomography (LORETA) in children with cochlear implants: a preliminary report.

PubMed

Henkin, Yael; Kishon-Rabin, Liat; Tatin-Schneider, Simona; Urbach, Doron; Hildesheimer, Minka; Kileny, Paul R

2004-12-01

The current preliminary report describes the utilization of low-resolution electromagnetic tomography (LORETA) in a small group of highly performing children using the Nucleus 22 cochlear implant (CI) and in normal-hearing (NH) adults. LORETA current density estimations were performed on an averaged target P3 component that was elicited by non-speech and speech oddball discrimination tasks. The results indicated that, when stimulated with tones, patients with right implants and NH adults (regardless of stimulated ear) showed enhanced activation in the right temporal lobe, whereas patients with left implants showed enhanced activation in the left temporal lobe. When stimulated with speech, patients with right implants showed bilateral activation of the temporal and frontal lobes, whereas patients with left implants showed only left temporal lobe activation. NH adults (regardless of stimulated ear) showed enhanced bilateral activation of the temporal and parietal lobes. The differences in activation patterns between patients with CI and NH subjects may be attributed to the long-term exposure to degraded input conditions which may have resulted in reorganization in terms of functional specialization. The difference between patients with right versus left implants, however, is intriguing and requires further investigation.
Fitting prelingually deafened adult cochlear implant users based on electrode discrimination performance.

PubMed

Debruyne, Joke A; Francart, Tom; Janssen, A Miranda L; Douma, Kim; Brokx, Jan P L

2017-03-01

This study investigated the hypotheses that (1) prelingually deafened CI users do not have perfect electrode discrimination ability and (2) the deactivation of non-discriminable electrodes can improve auditory performance. Electrode discrimination difference limens were determined for all electrodes of the array. The subjects' basic map was subsequently compared to an experimental map, which contained only discriminable electrodes, with respect to speech understanding in quiet and in noise, listening effort, spectral ripple discrimination and subjective appreciation. Subjects were six prelingually deafened, late implanted adults using the Nucleus cochlear implant. Electrode discrimination difference limens across all subjects and electrodes ranged from 0.5 to 7.125, with significantly larger limens for basal electrodes. No significant differences were found between the basic map and the experimental map on auditory tests. Subjective appreciation was found to be significantly poorer for the experimental map. Prelingually deafened CI users were unable to discriminate between all adjacent electrodes. There was no difference in auditory performance between the basic and experimental map. Potential factors contributing to the absence of improvement with the experimental map include the reduced number of maxima, incomplete adaptation to the new frequency allocation, and the mainly basal location of deactivated electrodes.
DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Hee Yoon; Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California; Raphael, Patrick D.

Cochlear amplification has been most commonly investigated by measuring the vibrations of the basilar membrane in animal models. Several different techniques have been used for measuring these vibrations such as laser Doppler vibrometry, miniature pressure sensors, low coherence interferometry, and spectral-domain optical coherence tomography (SD-OCT). We have built a swept-source OCT (SS-OCT) system, which is similar to SD-OCT in that it is capable of performing both imaging and vibration measurements within the mouse cochlea in vivo without having to open the bone. In vivo 3D images of a mouse cochlea were obtained, and the basilar membrane, tectorial membrane, Reissner’s membrane,more » tunnel of Corti, and reticular lamina could all be resolved. We measured vibrations of multiple structures within the mouse cochlea to sound stimuli. As well, we measured the radial deflections of the reticular lamina and tectorial membrane to estimate the displacement of the outer hair cell stereocilia. These measurements have the potential to more clearly define the mechanisms underlying the linear and non-linear processes within the mammalian cochlea.« less
Mechanisms of Hearing Loss after Blast Injury to the Ear

PubMed Central

Cho, Sung-Il; Gao, Simon S.; Xia, Anping; Wang, Rosalie; Salles, Felipe T.; Raphael, Patrick D.; Abaya, Homer; Wachtel, Jacqueline; Baek, Jongmin; Jacobs, David; Rasband, Matthew N.; Oghalai, John S.

2013-01-01

Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of increasing interest. The ear is the most common organ affected by blast injury because it is the body’s most sensitive pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes, indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory dysfunction. PMID:23840874
A thalamic input to the nucleus accumbens mediates opiate dependence.

PubMed

Zhu, Yingjie; Wienecke, Carl F R; Nachtrab, Gregory; Chen, Xiaoke

2016-02-11

Chronic opiate use induces opiate dependence, which is characterized by extremely unpleasant physical and emotional feelings after drug use is terminated. Both the rewarding effects of a drug and the desire to avoid withdrawal symptoms motivate continued drug use, and the nucleus accumbens is important for orchestrating both processes. While multiple inputs to the nucleus accumbens regulate reward, little is known about the nucleus accumbens circuitry underlying withdrawal. Here we identify the paraventricular nucleus of the thalamus as a prominent input to the nucleus accumbens mediating the expression of opiate-withdrawal-induced physical signs and aversive memory. Activity in the paraventricular nucleus of the thalamus to nucleus accumbens pathway is necessary and sufficient to mediate behavioural aversion. Selectively silencing this pathway abolishes aversive symptoms in two different mouse models of opiate withdrawal. Chronic morphine exposure selectively potentiates excitatory transmission between the paraventricular nucleus of the thalamus and D2-receptor-expressing medium spiny neurons via synaptic insertion of GluA2-lacking AMPA receptors. Notably, in vivo optogenetic depotentiation restores normal transmission at these synapses and robustly suppresses morphine withdrawal symptoms. This links morphine-evoked pathway- and cell-type-specific plasticity in the paraventricular nucleus of the thalamus to nucleus accumbens circuit to opiate dependence, and suggests that reprogramming this circuit holds promise for treating opiate addiction.
Brainstem Alzheimer’s-Like Pathology in the Triple Transgenic Mouse Model of Alzheimer’s Disease

PubMed Central

Overk, Cassia R.; Kelley, Christy M.; Mufson, Elliott J.

2011-01-01

The triple transgenic mouse (3xTgAD), harboring human APPSwe, PS1M146V and TauP301L genes, develops age-dependent forebrain intraneuronal Aβ and tau and extraneuronal plaques. We evaluated brainstem AD-like pathology using 6E10, AT8, and Alz50 antibodies and unbiased stereology in young and old 3xTgAD mice. Intraneuronal Aβ occurred in the tectum, periaqueductal gray, substantia nigra, red nucleus, tegmentum and mesencephalic V nucleus at all ages. Aβ-positive neuron numbers significantly decreased in the superior colliculus and substantia nigra while AT8-positive superior colliculus, red nucleus, principal sensory V, vestibular nuclei, and tegmental neurons significantly increased between 2 and 12 months. Alz50-positive neuron numbers increased only in the inferior colliculus between these ages. Dual labeling revealed a few Aβ- and tau- positive neurons. Plaques occurred only in the pons of female 3xTgAD mice starting at 9 months. 3xTgAD mice provide a platform to define in vivo mechanisms of Aβ and tau brainstem pathology. PMID:19524671
Nuclear Chk1 prevents premature mitotic entry.

PubMed

Matsuyama, Makoto; Goto, Hidemasa; Kasahara, Kousuke; Kawakami, Yoshitaka; Nakanishi, Makoto; Kiyono, Tohru; Goshima, Naoki; Inagaki, Masaki

2011-07-01

Chk1 inhibits the premature activation of the cyclin-B1-Cdk1. However, it remains controversial whether Chk1 inhibits Cdk1 in the centrosome or in the nucleus before the G2-M transition. In this study, we examined the specificity of the mouse monoclonal anti-Chk1 antibody DCS-310, with which the centrosome was stained. Conditional Chk1 knockout in mouse embryonic fibroblasts reduced nuclear but not centrosomal staining with DCS-310. In Chk1(+/myc) human colon adenocarcinoma (DLD-1) cells, Chk1 was detected in the nucleus but not in the centrosome using an anti-Myc antibody. Through the combination of protein array and RNAi technologies, we identified Ccdc-151 as a protein that crossreacted with DCS-310 on the centrosome. Mitotic entry was delayed by expression of the Chk1 mutant that localized in the nucleus, although forced immobilization of Chk1 to the centrosome had little impact on the timing of mitotic entry. These results suggest that nuclear but not centrosomal Chk1 contributes to correct timing of mitotic entry.
Effects of various antipsychotic drugs upon the striatal concentrations of para-hydroxyphenylacetic acid and meta-hydroxyphenylacetic acid in the mouse.

PubMed Central

Juorio, A. V.; McQuade, P. S.

1983-01-01

The endogenous concentrations of p- and m-hydroxyphenylacetic acid in the mouse caudate nucleus were determined by a gas chromatographic or a gas chromatographic-mass spectrometric technique and the concentrations were about 30 and 11 ng g-1 respectively. The subcutaneous administration of (+)-butaclamol (1 mg kg-1), haloperidol (5 mg kg-1), molindone (100 mg kg-1), sulpiride (50 mg kg-1) or chlorpromazine (20 mg kg-1) increased the concentration of mouse striatal p- and m-hydroxyphenylacetic acid; the effects were observed at 2 h after drug administration. Lower doses of chlorpromazine (2 mg kg-1), haloperidol (0.2 mg kg-1) and molindone (2 mg kg-1) did not affect p- or m-hydroxyphenylacetic acid concentrations. The time course for the concentration changes produced by chlorpromazine (20 mg kg-1) revealed that the formation of the metabolites occurred within 30 min after its administration and that their efflux from the caudate nucleus took at least 4 h for p-hydroxyphenylacetic acid and more than 8 h for m-hydroxyphenylacetic acid. Promethazine and (-)-butaclamol which have chemical structures related to chlorpromazine or (+)-butaclamol respectively but which lack antipsychotic activity, produced no effect on striatal p- or m-hydroxyphenylacetic acid concentrations. The results suggest that antipsychotic drugs increase the utilization of mouse striatal p- and m-tyramine and that after use the amines are metabolized by monoamine oxidase to form p- or m-hydroxyphenylacetic acid. The synthesis of the acid metabolites occurs within 30 min after chlorpromazine administration and their efflux from the caudate nucleus takes from 4-8 h. PMID:6196070
Relative roles of different mechanisms of depression at the mouse endbulb of Held

PubMed Central

Yang, Hua; Xu-Friedman, Matthew A.

2010-01-01

Several mechanisms can underlie short-term synaptic depression, including vesicle depletion, receptor desensitization, and changes in presynaptic release probability. To determine which mechanisms affect depression under physiological conditions, we studied the synapse formed by auditory nerve fibers onto bushy cells in the anteroventral cochlear nucleus (the “endbulb of Held”) using voltage-clamp recordings of brain slices from P15–21 mice near physiological temperatures. Depression of both AMPA and NMDA EPSCs showed two phases of recovery. The fast component of depression for the AMPA EPSC was eliminated by cyclothiazide and aniracetam, suggesting it results from desensitization. The fast component of depression for the NMDA EPSC was reduced by the low-affinity antagonist L-AP5, suggesting it results from saturation. The remaining depression in AMPA and NMDA components is identical and therefore presynaptic in origin. It is likely to result from presynaptic vesicle depletion. Recovery from depression after trains of activity was slowed by the application of EGTA-AM, suggesting that the endbulb has a residual-calcium-dependent form of recovery. We developed a model that incorporates depletion, desensitization, and calcium-dependent recovery. This model replicated experimental findings over a range of experimental conditions. The model further indicated that desensitization plays only a minor role during prolonged activity, in large part because presynaptic release is so depleted. Thus, depletion appears to be the dominant mechanism of depression at the endbulb during normal activity. Furthermore, calcium-dependent recovery at the endbulb is critical to prevent complete run-down during high activity and to preserve the reliability of information transmission. PMID:18367696
The Brainstem Tau Cytoskeletal Pathology of Alzheimer's Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance.

PubMed

Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Turco, Domenico Del; Seidel, Kay; Dunnen, Wilfred den; Korf, Horst-Werner

2016-01-01

The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the ascending dopaminergic, cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending serotonergic system. In contrast to the cerebral cortex the affection of the brainstem in Alzheimer's disease (AD) by the neurofibrillary or tau cytoskeletal pathology was recognized only approximately fourty years ago in initial brainstem studies. Detailed pathoanatomical investigations of silver stained or tau immunostained brainstem tissue sections revealed nerve cell loss and prominent ADrelated cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations, dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades, dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction and brain spread of the AD-related cytoskeletal pathology.
The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival

NASA Technical Reports Server (NTRS)

Wallis, Deeann; Hamblen, Melanie; Zhou, Yi; Venken, Koen J T.; Schumacher, Armin; Grimes, H. Leighton; Zoghbi, Huda Y.; Orkin, Stuart H.; Bellen, Hugo J.

2003-01-01

Gfi1 was first identified as causing interleukin 2-independent growth in T cells and lymphomagenesis in mice. Much work has shown that Gfi1 and Gfi1b, a second mouse homolog, play pivotal roles in blood cell lineage differentiation. However, neither Gfi1 nor Gfi1b has been implicated in nervous system development, even though their invertebrate homologues, senseless in Drosophila and pag-3 in C. elegans are expressed and required in the nervous system. We show that Gfi1 mRNA is expressed in many areas that give rise to neuronal cells during embryonic development in mouse, and that Gfi1 protein has a more restricted expression pattern. By E12.5 Gfi1 mRNA is expressed in both the CNS and PNS as well as in many sensory epithelia including the developing inner ear epithelia. At later developmental stages, Gfi1 expression in the ear is refined to the hair cells and neurons throughout the inner ear. Gfi1 protein is expressed in a more restricted pattern in specialized sensory cells of the PNS, including the eye, presumptive Merkel cells, the lung and hair cells of the inner ear. Gfi1 mutant mice display behavioral defects that are consistent with inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. They have a unique inner ear phenotype in that the vestibular and cochlear hair cells are differentially affected. Although Gfi1-deficient mice initially specify inner ear hair cells, these hair cells are disorganized in both the vestibule and cochlea. The outer hair cells of the cochlea are improperly innervated and express neuronal markers that are not normally expressed in these cells. Furthermore, Gfi1 mutant mice lose all cochlear hair cells just prior to and soon after birth through apoptosis. Finally, by five months of age there is also a dramatic reduction in the number of cochlear neurons. Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death.
The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

PubMed

Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

2015-12-01

Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of Biologists Ltd.
Dose-dependent effects of ouabain on spiral ganglion neurons and Schwann cells in mouse cochlea.

PubMed

Zhang, Zhi-Jian; Guan, Hong-Xia; Yang, Kun; Xiao, Bo-Kui; Liao, Hua; Jiang, Yang; Zhou, Tao; Hua, Qing-Quan

2017-10-01

This study aimed in fully investigating the toxicities of ouabain to mouse cochlea and the related cellular environment, and providing an optimal animal model system for cell transplantation in the treatment of auditory neuropathy (AN) and sensorineural hearing loss (SNHL). Different dosages of ouabain were applied to mouse round window. The auditory brainstem responses and distortion product otoacoustic emissions were used to evaluate the cochlear function. The immunohistochemical staining and cochlea surface preparation were performed to detect the spiral ganglion neurons (SGNs), Schwann cells and hair cells. Ouabain at the dosages of 0.5 mM, 1 mM and 3 mM selectively and permanently destroyed SGNs and their functions, while leaving the hair cells relatively intact. Ouabain at 3 mM resulted in the most severe SGNs loss and induced significant loss of Schwann cells started as early as 7 days and with further damages at 14 and 30 days after ouabain exposure. The application of ouabain to mouse round window induces damages of SGNs and Schwann cells in a dose- and time-dependent manner, this study established a reliable and accurate animal model system of AN and SNHL.
Reliability Measure of a Clinical Test: Appreciation of Music in Cochlear Implantees (AMICI)

PubMed Central

Cheng, Min-Yu; Spitzer, Jaclyn B.; Shafiro, Valeriy; Sheft, Stanley; Mancuso, Dean

2014-01-01

Purpose The goals of this study were (1) to investigate the reliability of a clinical music perception test, Appreciation of Music in Cochlear Implantees (AMICI), and (2) examine associations between the perception of music and speech. AMICI was developed as a clinical instrument for assessing music perception in persons with cochlear implants (CIs). The test consists of four subtests: (1) music versus environmental noise discrimination, (2) musical instrument identification (closed-set), (3) musical style identification (closed-set), and (4) identification of musical pieces (open-set). To be clinically useful, it is crucial for AMICI to demonstrate high test-retest reliability, so that CI users can be assessed and retested after changes in maps or programming strategies. Research Design Thirteen CI subjects were tested with AMICI for the initial visit and retested again 10–14 days later. Two speech perception tests (consonant-nucleus-consonant [CNC] and Bamford-Kowal-Bench Speech-in-Noise [BKB-SIN]) were also administered. Data Analysis Test-retest reliability and equivalence of the test’s three forms were analyzed using paired t-tests and correlation coefficients, respectively. Correlation analysis was also conducted between results from the music and speech perception tests. Results Results showed no significant difference between test and retest (p > 0.05) with adequate power (0.9) as well as high correlations between the three forms (Forms A and B, r = 0.91; Forms A and C, r = 0.91; Forms B and C, r = 0.95). Correlation analysis showed high correlation between AMICI and BKB-SIN (r = −0.71), and moderate correlation between AMICI and CNC (r = 0.4). Conclusions The study showed AMICI is highly reliable for assessing musical perception in CI users. PMID:24384082
Comparative analysis of cadherin expression and connectivity patterns in the cerebellar system of ferret and mouse.

PubMed

Neudert, Franziska; Nuernberger, Krishna-K Monique; Redies, Christoph

2008-12-20

The cerebellum shows remarkable variations in the relative size of its divisions among vertebrate species. In the present study, we compare the cerebella of two mammals (ferret and mouse) by mapping the expression of three cadherins (cadherin-8, protocadherin-7, and protocadherin-10) at similar postnatal stages. The three cadherins are expressed differentially in parasagittal stripes in the cerebellar cortex, in the portions of the deep cerebellar nuclei, in the divisions of the inferior olivary nucleus, and in the lateral vestibular nucleus. The expression profiles suggest that the cadherin-positive structures are interconnected. The expression patterns resemble each other in ferret and mouse, although some differences can be observed. The general resemblance indicates that cerebellar organization is based on a common set of embryonic divisions in the two species. Consequently, the large differences in cerebellar morphology between the two species are more likely caused by differential growth of these embryonic divisions than by differences in early embryonic patterning. Based on the cadherin expression patterns, a model of corticonuclear projection territories in ferret and mouse is proposed. In summary, our results indicate that the cerebellar systems of rodents and carnivores display a relatively large degree of similarity in their molecular and functional organization.
In Vivo Validation of Custom-Designed Silicon-Based Microelectrode Arrays for Long-Term Neural Recording and Stimulation

PubMed Central

Manoonkitiwongsa, Panya S.; Wang, Cindy X.; McCreery, Douglas B.

2012-01-01

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays’ insertion forces have been quantified in vitro. Five consecutive chronically-implanted devices were fully functional from 3 to 18 months. The microelectrode sites were electroplated with iridium oxide, and the charge injection capacity measurements were performed both in vitro and after implantation in the adult feline brain. The functionality of the chronic array was validated by stimulating in the cochlear nucleus and recording the evoked neuronal activity in the central nucleus of the inferior colliculus. The arrays’ recording quality has also been quantified in vivo with neuronal spike activity recorded up to 566 days after implantation. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation. PMID:22020666
Crypto-rhombomeres of the mouse medulla oblongata, defined by molecular and morphological features.

PubMed

Tomás-Roca, Laura; Corral-San-Miguel, Rubén; Aroca, Pilar; Puelles, Luis; Marín, Faustino

2016-03-01

The medulla oblongata is the caudal portion of the vertebrate hindbrain. It contains major ascending and descending fiber tracts as well as several motor and interneuron populations, including neural centers that regulate the visceral functions and the maintenance of bodily homeostasis. In the avian embryo, it has been proposed that the primordium of this region is subdivided into five segments or crypto-rhombomeres (r7-r11), which were defined according to either their parameric position relative to intersomitic boundaries (Cambronero and Puelles, in J Comp Neurol 427:522-545, 2000) or a stepped expression of Hox genes (Marín et al., in Dev Biol 323:230-247, 2008). In the present work, we examine the implied similar segmental organization of the mouse medulla oblongata. To this end, we analyze the expression pattern of Hox genes from groups 3 to 8, comparing them to the expression of given cytoarchitectonic and molecular markers, from mid-gestational to perinatal stages. As a result of this approach, we conclude that the mouse medulla oblongata is segmentally organized, similarly as in avian embryos. Longitudinal structures such as the nucleus of the solitary tract, the dorsal vagal motor nucleus, the hypoglossal motor nucleus, the descending trigeminal and vestibular columns, or the reticular formation appear subdivided into discrete segmental units. Additionally, our analysis identified an internal molecular organization of the migrated pontine nuclei that reflects a differential segmental origin of their neurons as assessed by Hox gene expression.

A physiological frequency-position map of the chinchilla cochlea.

PubMed

Müller, Marcus; Hoidis, Silvi; Smolders, Jean W T

2010-09-01

Accumulating evidence indicates that mammalian cochlear frequency-position maps (location of maximum vibration of the basilar membrane as a function of frequency) depend on the physiological condition of the inner ear. Cochlear damage desensitizes the ear, after the damage the original location of maximum vibration is tuned to a lower sound frequency. This suggests that frequency-position maps, derived from such desensitized ears, are shifted to lower frequencies, corresponding to a shift of the basilar membrane vibration pattern towards the base for a given stimulus frequency. To test this hypothesis, we re-mapped the cochlear frequency-position map in the chinchilla. We collected frequency-position data from chinchillas in normal physiological condition ("physiological map") and compared these to data previously established from sound overexposed ears ("anatomical map"). The characteristic frequency (CF) of neurons in the cochlear nucleus was determined. Horse-radish peroxidase (HRP) or biocytin (BCT) were injected iontophoretically to trace auditory nerve fibers towards their innervation site in the organ of Corti. The relationship between distance from the base (d, percent) and frequency (f, kHz) was described best by a simple exponential function: d = 61.2 - 42.2 x log(f). The slope of the function was 2.55 mm/octave. Compared to the "anatomical map", the "physiological map" was shifted by about 0.3 octaves to higher frequencies corresponding to a shift of the basilar membrane vibration pattern of 0.8 mm towards the apex for a given stimulus frequency. Our findings affirm that frequency-position maps in the mammalian cochlea depend on the condition of the inner ear. Damage-induced desensitization in mammalian inner ears results in similar shifts of CF (about 0.5 octaves) but different shifts of the maximum of the vibration pattern towards the base at given frequencies, dependent on the mapping constant of the species, longer basilar membranes showing a larger basal shift. Furthermore, the results substantiate the notion that "crowding" at lower frequencies appears to be a specialization rather than a general feature. Copyright (c) 2010 Elsevier B.V. All rights reserved.
Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier

PubMed Central

Gao, Jiangang; Wang, Xiang; Wu, Xudong; Aguinaga, Sal; Huynh, Kristin; Jia, Shuping; Matsuda, Keiji; Patel, Manish; Zheng, Jing; Cheatham, MaryAnn; He, David Z.; Dallos, Peter; Zuo, Jian

2007-01-01

The remarkable sensitivity and frequency selectivity of the mammalian cochlea is attributed to a unique amplification process that resides in outer hair cells (OHCs). Although the mammalian-specific somatic motility is considered a substrate of cochlear amplification, it has also been proposed that somatic motility in mammals simply acts as an operating-point adjustment for the ubiquitous stereocilia-based amplifier. To address this issue, we created a mouse model in which a mutation (C1) was introduced into the OHC motor protein prestin, based on previous results in transfected cells. In C1/C1 knockin mice, localization of C1-prestin, as well as the length and number of OHCs, were all normal. In OHCs isolated from C1/C1 mice, nonlinear capacitance and somatic motility were both shifted toward hyperpolarization, so that, compared with WT controls, the amplitude of cycle-by-cycle (alternating, or AC) somatic motility remained the same, but the unidirectional (DC) component reversed polarity near the OHC's presumed in vivo resting membrane potential. No physiological defects in cochlear sensitivity or frequency selectivity were detected in C1/C1 or C1/+ mice. Hence, our results do not support the idea that OHC somatic motility adjusts the operating point of a stereocilia-based amplifier. However, they are consistent with the notion that the AC component of OHC somatic motility plays a dominant role in mammalian cochlear amplification. PMID:17640919
The timecourse of apoptotic cell death during postnatal remodeling of the mouse cochlea and its premature onset by triiodothyronine (T3).

PubMed

Peeters, R P; Ng, L; Ma, M; Forrest, D

2015-05-15

Apoptosis underlies various forms of tissue remodeling during development. Prior to the onset of hearing, thyroid hormone (T3) promotes cochlear remodeling, which involves regression of the greater epithelial ridge (GER), a transient structure of columnar cells adjacent to the mechanosensory hair cells. We investigated the timecourse of apoptosis in the GER and the influence of ectopic T3 on apoptosis. In saline-treated mice, activated caspase 3-positive cells were detected in the GER between postnatal days 7 and 13 and appeared progressively along the cochlear duct from base to apex over developmental time. T3 given on P0 and P1 advanced the overall program of apoptosis and remodeling by ~4 days. Thyroid hormone receptor β was required for these actions, suggesting a receptor-mediated process of initiation of apoptosis. Finally, T3 given only at P0 or P1 resulted in deafness in adult mice, thus revealing a transient period of susceptibility to long-term damage in the neonatal auditory system. Published by Elsevier Ireland Ltd.
Cell migration, intercalation and growth regulate mammalian cochlear extension.

PubMed

Driver, Elizabeth Carroll; Northrop, Amy; Kelley, Matthew W

2017-10-15

Developmental remodeling of the sensory epithelium of the cochlea is required for the formation of an elongated, tonotopically organized auditory organ, but the cellular processes that mediate these events are largely unknown. We used both morphological assessments of cellular rearrangements and time-lapse imaging to visualize cochlear remodeling in mouse. Analysis of cell redistribution showed that the cochlea extends through a combination of radial intercalation and cell growth. Live imaging demonstrated that concomitant cellular intercalation results in a brief period of epithelial convergence, although subsequent changes in cell size lead to medial-lateral spreading. Supporting cells, which retain contact with the basement membrane, exhibit biased protrusive activity and directed movement along the axis of extension. By contrast, hair cells lose contact with the basement membrane, but contribute to continued outgrowth through increased cell size. Regulation of cellular protrusions, movement and intercalation within the cochlea all require myosin II. These results establish, for the first time, many of the cellular processes that drive the distribution of sensory cells along the tonotopic axis of the cochlea. © 2017. Published by The Company of Biologists Ltd.
Mode-Locked Spike Trains in Responses of Ventral Cochlear Nucleus Chopper and Onset Neurons to Periodic Stimuli

PubMed Central

Laudanski, Jonathan; Coombes, Stephen; Palmer, Alan R.

2010-01-01

We report evidence of mode-locking to the envelope of a periodic stimulus in chopper units of the ventral cochlear nucleus (VCN). Mode-locking is a generalized description of how responses in periodically forced nonlinear systems can be closely linked to the input envelope, while showing temporal patterns of higher order than seen during pure phase-locking. Re-analyzing a previously unpublished dataset in response to amplitude modulated tones, we find that of 55% of cells (6/11) demonstrated stochastic mode-locking in response to sinusoidally amplitude modulated (SAM) pure tones at 50% modulation depth. At 100% modulation depth SAM, most units (3/4) showed mode-locking. We use interspike interval (ISI) scattergrams to unravel the temporal structure present in chopper mode-locked responses. These responses compared well to a leaky integrate-and-fire model (LIF) model of chopper units. Thus the timing of spikes in chopper unit responses to periodic stimuli can be understood in terms of the complex dynamics of periodically forced nonlinear systems. A larger set of onset (33) and chopper units (24) of the VCN also shows mode-locked responses to steady-state vowels and cosine-phase harmonic complexes. However, while 80% of chopper responses to complex stimuli meet our criterion for the presence of mode-locking, only 40% of onset cells show similar complex-modes of spike patterns. We found a correlation between a unit's regularity and its tendency to display mode-locked spike trains as well as a correlation in the number of spikes per cycle and the presence of complex-modes of spike patterns. These spiking patterns are sensitive to the envelope as well as the fundamental frequency of complex sounds, suggesting that complex cell dynamics may play a role in encoding periodic stimuli and envelopes in the VCN. PMID:20042702
An Independent Construct for Conditional Expression of Atonal Homolog-1

PubMed Central

Cheng, Yen-fu; Kinouchi, Hikaru; Bieber, Rebecca; Edge, Albert S.B.

2014-01-01

Abstract The mammalian homolog of the basic helix-loop-helix transcription factor atonal-1 (Atoh1 or Math1) is required for development of cochlear hair cells that function as the mechanosensory cells required for audition. Forced expression of Atoh1 in cochlear-supporting cells may provide a way to regenerate hair cells and provide for a therapy for hearing loss. Additionally, Atoh1 is an inhibitor of proliferation and has further clinical applications in anticancer therapies. The goal of these experiments was to improve the method for Atoh1 expression by engineering a genetic construct that may be used in future translational applications. To address the poor control of Atoh1 expression in standard gene expression systems where Atoh1 is expressed constitutively at abnormally elevated levels, our aim was to engineer an inducible system whereby Atoh1 was upregulated by an inducer and downregulated once the inducer was removed. A further aim was to engineer a single genetic construct that allowed for conditional expression of Atoh1 independent of secondary regulatory elements. Here we describe a stand-alone genetic construct that utilizes the tamoxifen sensitivity of a mutated estrogen receptor (ER) ligand-binding domain for the conditional expression of Atoh1. The Atoh1-ER-DsRed construct is translated into an ATOH1-ER-DSRED fusion protein that remains sequestered in the cytoplasm and therefore rendered inactive because it cannot enter the nucleus to activate Atoh1 signaling pathways. However, application of 4-hydroxytamoxifen results in translocation of the fusion protein to the nucleus, where it binds to the Atoh1 enhancer, upregulates transcription and translation of endogenous ATOH1 and activates downstream Atoh1 signaling such as upregulation of the hair cell protein MYOSIN 7A. Removal of tamoxifen reverses the upregulation of endogenous Atoh1 signaling. This construct serves as an independent genetic construct that allows for the conditional upregulation and downregulation of Atoh1, and may prove useful for manipulating Atoh1 expression in vivo. PMID:24066662
Partial tripolar cochlear implant stimulation: Spread of excitation and forward masking in the inferior colliculus.

PubMed

Bierer, Julie Arenberg; Bierer, Steven M; Middlebrooks, John C

2010-12-01

This study examines patterns of neural activity in response to single biphasic electrical pulses, presented alone or following a forward masking pulse train, delivered by a cochlear implant. Recordings were made along the tonotopic axis of the central nucleus of the inferior colliculus (ICC) in ketamine/xylazine anesthetized guinea pigs. The partial tripolar electrode configuration was used, which provided a systematic way to vary the tonotopic extent of ICC activation between monopolar (broad) and tripolar (narrow) extremes while maintaining the same peak of activation. The forward masking paradigm consisted of a 200 ms masker pulse train (1017 pulses per second) followed 10 ms later by a single-pulse probe stimulus; the current fraction of the probe was set to 0 (monopolar), 1 (tripolar), or 0.5 (hybrid), and the fraction of the masker was fixed at 0.5. Forward masking tuning profiles were derived from the amount of masking current required to just suppress the activity produced by a fixed-level probe. These profiles were sharper for more focused probe configurations, approximating the pattern of neural activity elicited by single (non-masked) pulses. The result helps to bridge the gap between previous findings in animals and recent psychophysical data. Copyright © 2010 Elsevier B.V. All rights reserved.
Partial tripolar cochlear implant stimulation: Spread of excitation and forward masking in the inferior colliculus

PubMed Central

Bierer, Julie Arenberg; Bierer, Steven M.; Middlebrooks, John C.

2010-01-01

This study examines patterns of neural activity in response to single biphasic electrical pulses, presented alone or following a forward masking pulse train, delivered by a cochlear implant. Recordings were made along the tonotopic axis of the central nucleus of the inferior colliculus (ICC) in ketamine/xylazine anesthetized guinea pigs. The partial tripolar electrode configuration was used, which provided a systematic way to vary the tonotopic extent of ICC activation between monopolar (broad) and tripolar (narrow) extremes while maintaining the same peak of activation. The forward masking paradigm consisted of a 200-ms masker pulse train (1017 pulses per second) followed 10 ms later by a single-pulse probe stimulus; the current fraction of the probe was set to 0 (monopolar), 1 (tripolar), or 0.5 (hybrid), and the fraction of the masker was fixed at 0.5. Forward masking tuning profiles were derived from the amount of masking current required to just suppress the activity produced by a fixed-level probe. These profiles were sharper for more focused probe configurations, approximating the pattern of neural activity elicited by single (non-masked) pulses. The result helps to bridge the gap between previous findings in animals and recent psychophysical data. PMID:20727397
Effects of stimulation configurations on place pitch discrimination in cochlear implants.

PubMed

Kwon, Bomjun J; Perry, Trevor T; Olmstead, Vauna L

2011-06-01

The present study aimed to examine the effect of electrode configuration, specifically monopolar (MP) or bipolar (BP) stimulation, on place pitch discrimination in cochlear implants (CIs). Twelve subjects implanted with the Nucleus Freedom device were presented with various pairs of stimulation across the electrode array, with varying degrees of distance between stimulation sites, and asked to judge the higher of the two in pitch. Each pair was presented either in the same mode or in different modes of stimulation for the within-mode or across-mode condition, respectively, at least 20 times. The result of the within-mode condition revealed that subjects, on average, were able to discriminate pitches significantly better in MP than in BP, with the sensitivity index (d') for adjacent channels of 1.2 for MP and 0.8 for BP. The result of the across-mode condition revealed that while individual variability existed, there was a strong tendency for CI subjects to perceive a higher pitch in BP stimulation than in MP for a similar site of stimulation. In other words, an MP channel needed to be shifted in a basal direction by as much as two electrodes on average to elicit a pitch comparable to that of a BP channel. © 2011 Acoustical Society of America
Environmental Sound Training in Cochlear Implant Users

PubMed Central

Sheft, Stanley; Kuvadia, Sejal; Gygi, Brian

2015-01-01

Purpose The study investigated the effect of a short computer-based environmental sound training regimen on the perception of environmental sounds and speech in experienced cochlear implant (CI) patients. Method Fourteen CI patients with the average of 5 years of CI experience participated. The protocol consisted of 2 pretests, 1 week apart, followed by 4 environmental sound training sessions conducted on separate days in 1 week, and concluded with 2 posttest sessions, separated by another week without training. Each testing session included an environmental sound test, which consisted of 40 familiar everyday sounds, each represented by 4 different tokens, as well as the Consonant Nucleus Consonant (CNC) word test, and Revised Speech Perception in Noise (SPIN-R) sentence test. Results Environmental sounds scores were lower than for either of the speech tests. Following training, there was a significant average improvement of 15.8 points in environmental sound perception, which persisted 1 week later after training was discontinued. No significant improvements were observed for either speech test. Conclusions The findings demonstrate that environmental sound perception, which remains problematic even for experienced CI patients, can be improved with a home-based computer training regimen. Such computer-based training may thus provide an effective low-cost approach to rehabilitation for CI users, and potentially, other hearing impaired populations. PMID:25633579
Effects of chronic exposure to electromagnetic waves on the auditory system.

PubMed

Özgür, Abdulkadir; Tümkaya, Levent; Terzi, Suat; Kalkan, Yıldıray; Erdivanlı, Özlem Çelebi; Dursun, Engin

2015-08-01

The results support that chronic electromagnetic field exposure may cause damage by leading to neuronal degeneration of the auditory system. Numerous researches have been done about the risks of exposure to the electromagnetic fields that occur during the use of these devices, especially the effects on hearing. The aim of this study is to evaluate the effects of the electromagnetic waves emitted by the mobile phones through the electrophysiological and histological methods. Twelve adult Wistar albino rats were included in the study. The rats were divided into two groups of six rats. The study group was exposed to the electromagnetic waves over a period of 30 days. The control group was not given any exposure to the electromagnetic fields. After the completion of the electromagnetic wave application, the auditory brainstem responses of both groups were recorded under anesthesia. The degeneration of cochlear nuclei was graded by two different histologists, both of whom were blinded to group information. The histopathologic and immunohistochemical analysis showed neuronal degeneration signs, such as increased vacuolization in the cochlear nucleus, pyknotic cell appearance, and edema in the group exposed to the electromagnetic fields compared to the control group. The average latency of wave in the ABR was similar in both groups (p > 0.05).
Relationships among vocabulary size, nonverbal cognition, and spoken word recognition in adults with cochlear implants

NASA Astrophysics Data System (ADS)

Collison, Elizabeth A.; Munson, Benjamin; Carney, Arlene E.

2002-05-01

Recent research has attempted to identify the factors that predict speech perception performance among users of cochlear implants (CIs). Studies have found that approximately 20%-60% of the variance in speech perception scores can be accounted for by factors including duration of deafness, etiology, type of device, and length of implant use, leaving approximately 50% of the variance unaccounted for. The current study examines the extent to which vocabulary size and nonverbal cognitive ability predict CI listeners' spoken word recognition. Fifteen postlingually deafened adults with nucleus or clarion CIs were given standardized assessments of nonverbal cognitive ability and expressive vocabulary size: the Expressive Vocabulary Test, the Test of Nonverbal Intelligence-III, and the Woodcock-Johnson-III Test of Cognitive Ability, Verbal Comprehension subtest. Two spoken word recognition tasks were administered. In the first, listeners identified isophonemic CVC words. In the second, listeners identified gated words varying in lexical frequency and neighborhood density. Analyses will examine the influence of lexical frequency and neighborhood density on the uniqueness point in the gating task, as well as relationships among nonverbal cognitive ability, vocabulary size, and the two spoken word recognition measures. [Work supported by NIH Grant P01 DC00110 and by the Lions 3M Hearing Foundation.
The effect of presentation level and stimulation rate on speech perception and modulation detection for cochlear implant users.

PubMed

Brochier, Tim; McDermott, Hugh J; McKay, Colette M

2017-06-01

In order to improve speech understanding for cochlear implant users, it is important to maximize the transmission of temporal information. The combined effects of stimulation rate and presentation level on temporal information transfer and speech understanding remain unclear. The present study systematically varied presentation level (60, 50, and 40 dBA) and stimulation rate [500 and 2400 pulses per second per electrode (pps)] in order to observe how the effect of rate on speech understanding changes for different presentation levels. Speech recognition in quiet and noise, and acoustic amplitude modulation detection thresholds (AMDTs) were measured with acoustic stimuli presented to speech processors via direct audio input (DAI). With the 500 pps processor, results showed significantly better performance for consonant-vowel nucleus-consonant words in quiet, and a reduced effect of noise on sentence recognition. However, no rate or level effect was found for AMDTs, perhaps partly because of amplitude compression in the sound processor. AMDTs were found to be strongly correlated with the effect of noise on sentence perception at low levels. These results indicate that AMDTs, at least when measured with the CP910 Freedom speech processor via DAI, explain between-subject variance of speech understanding, but do not explain within-subject variance for different rates and levels.
L-baclofen-sensitive GABAB binding sites in the medial vestibular nucleus localized by immunocytochemistry

NASA Technical Reports Server (NTRS)

Holstein, G. R.; Martinelli, G. P.; Cohen, B.

1992-01-01

L-Baclofen-sensitive GABAB binding sites in the medial vestibular nucleus (MVN) were identified immunocytochemically and visualized ultrastructurally in L-baclofen-preinjected rats and monkeys, using a mouse monoclonal antibody with specificity for the p-chlorophenyl moiety of baclofen. Saline-preinjected animals showed no immunostain. In drug-injected animals, there was evidence for both pre- and postsynaptic GABAergic inhibition in MVN mediated by GABAB receptors. These neural elements could be utilized in control of velocity storage in the vestibulo-ocular reflex.
Stem/progenitor cells derived from the cochlear sensory epithelium give rise to spheres with distinct morphologies and features.

PubMed

Diensthuber, Marc; Oshima, Kazuo; Heller, Stefan

2009-06-01

Nonmammalian vertebrates regenerate lost sensory hair cells by means of asymmetric division of supporting cells. Inner ear or lateral line supporting cells in birds, amphibians, and fish consequently serve as bona fide stem cells resulting in high regenerative capacity of hair cell-bearing organs. Hair cell regeneration does not happen in the mammalian cochlea, but cells with proliferative capacity can be isolated from the neonatal cochlea. These cells have the ability to form clonal floating colonies, so-called spheres, when cultured in nonadherent conditions. We noticed that the sphere population derived from mouse cochlear sensory epithelium cells was heterogeneous, consisting of morphologically distinct sphere types, hereby classified as solid, transitional, and hollow. Cochlear sensory epithelium-derived stem/progenitor cells initially give rise to small solid spheres, which subsequently transition into hollow spheres, a change that is accompanied by epithelial differentiation of the majority of sphere cells. Only solid spheres, and to a lesser extent, transitional spheres, appeared to harbor self-renewing stem cells, whereas hollow spheres could not be consistently propagated. Solid spheres contained significantly more rapidly cycling Pax-2-expressing presumptive otic progenitor cells than hollow spheres. Islet-1, which becomes upregulated in nascent sensory patches, was also more abundant in solid than in hollow spheres. Likewise, hair cell-like cells, characterized by the expression of multiple hair cell markers, differentiated in significantly higher numbers in cell populations derived from solid spheres. We conclude that cochlear sensory epithelium cell populations initially give rise to small solid spheres that have self-renewing capacity before they subsequently convert into hollow spheres, a process that is accompanied by loss of stemness and reduced ability to spontaneously give rise to hair cell-like cells. Solid spheres might, therefore, represent the most suitable sphere type for cell-based assays or animal model transplantation studies aimed at development of cell replacement therapies.
Electromagnetic versus electrical coupling of personal frequency modulation (FM) receivers to cochlear implant sound processors.

PubMed

Schafer, Erin C; Romine, Denise; Musgrave, Elizabeth; Momin, Sadaf; Huynh, Christy

2013-01-01

Previous research has suggested that electrically coupled frequency modulation (FM) systems substantially improved speech-recognition performance in noise in individuals with cochlear implants (CIs). However, there is limited evidence to support the use of electromagnetically coupled (neck loop) FM receivers with contemporary CI sound processors containing telecoils. The primary goal of this study was to compare speech-recognition performance in noise and subjective ratings of adolescents and adults using one of three contemporary CI sound processors coupled to electromagnetically and electrically coupled FM receivers from Oticon. A repeated-measures design was used to compare speech-recognition performance in noise and subjective ratings without and with the FM systems across three test sessions (Experiment 1) and to compare performance at different FM-gain settings (Experiment 2). Descriptive statistics were used in Experiment 3 to describe output differences measured through a CI sound processor. Experiment 1 included nine adolescents or adults with unilateral or bilateral Advanced Bionics Harmony (n = 3), Cochlear Nucleus 5 (n = 3), and MED-EL OPUS 2 (n = 3) CI sound processors. In Experiment 2, seven of the original nine participants were tested. In Experiment 3, electroacoustic output was measured from a Nucleus 5 sound processor when coupled to the electromagnetically coupled Oticon Arc neck loop and electrically coupled Oticon R2. In Experiment 1, participants completed a field trial with each FM receiver and three test sessions that included speech-recognition performance in noise and a subjective rating scale. In Experiment 2, participants were tested in three receiver-gain conditions. Results in both experiments were analyzed using repeated-measures analysis of variance. Experiment 3 involved electroacoustic-test measures to determine the monitor-earphone output of the CI alone and CI coupled to the two FM receivers. The results in Experiment 1 suggested that both FM receivers provided significantly better speech-recognition performance in noise than the CI alone; however, the electromagnetically coupled receiver provided significantly better speech-recognition performance in noise and better ratings in some situations than the electrically coupled receiver when set to the same gain. In Experiment 2, the primary analysis suggested significantly better speech-recognition performance in noise for the neck-loop versus electrically coupled receiver, but a second analysis, using the best performance across gain settings for each device, revealed no significant differences between the two FM receivers. Experiment 3 revealed monitor-earphone output differences in the Nucleus 5 sound processor for the two FM receivers when set to the +8 setting used in Experiment 1 but equal output when the electrically coupled device was set to a +16 gain setting and the electromagnetically coupled device was set to the +8 gain setting. Individuals with contemporary sound processors may show more favorable speech-recognition performance in noise electromagnetically coupled FM systems (i.e., Oticon Arc), which is most likely related to the input processing and signal processing pathway within the CI sound processor for direct input versus telecoil input. Further research is warranted to replicate these findings with a larger sample size and to develop and validate a more objective approach to fitting FM systems to CI sound processors. American Academy of Audiology.
On the intracellular trafficking of mouse S5 ribosomal protein from cytoplasm to nucleoli.

PubMed

Matragkou, Ch; Papachristou, H; Karetsou, Z; Papadopoulos, G; Papamarcaki, T; Vizirianakis, I S; Tsiftsoglou, A S; Choli-Papadopoulou, T

2009-10-09

The non-ribosomal functions of mammalian ribosomal proteins have recently attracted worldwide attention. The mouse ribosomal protein S5 (rpS5) derived from ribosomal material is an assembled non-phosphorylated protein. The free form of rpS5 protein, however, undergoes phosphorylation. In this study, we have (a) investigated the potential role of phosphorylation in rpS5 protein transport into the nucleus and then into nucleoli and (b) determined which of the domains of rpS5 are involved in this intracellular trafficking. In vitro PCR mutagenesis of mouse rpS5 cDNA, complemented by subsequent cloning and expression of rpS5 truncated recombinant forms, produced in fusion with green fluorescent protein, permitted the investigation of rpS5 intracellular trafficking in HeLa cells using confocal microscopy complemented by Western blot analysis. Our results indicate the following: (a) rpS5 protein enters the nucleus via the region 38-50 aa that forms a random coil as revealed by molecular dynamic simulation. (b) Immunoprecipitation of rpS5 with casein kinase II and immobilized metal affinity chromatography analysis complemented by in vitro kinase assay revealed that phosphorylation of rpS5 seems to be indispensable for its transport from nucleus to nucleoli; upon entering the nucleus, Thr-133 phosphorylation triggers Ser-24 phosphorylation by casein kinase II, thus promoting entrance of rpS5 into the nucleoli. Another important role of rpS5 N-terminal region is proposed to be the regulation of protein's cellular level. The repetitively co-appearance of a satellite C-terminal band below the entire rpS5 at the late stationary phase, and not at the early logarithmic phase, of cell growth suggests a specific degradation balancing probably the unassembled ribosomal protein molecules with those that are efficiently assembled to ribosomal subunits. Overall, these data provide new insights on the structural and functional domains within the rpS5 molecule that contribute to its cellular functions.
Mouse Nuclear Myosin I Knock-Out Shows Interchangeability and Redundancy of Myosin Isoforms in the Cell Nucleus

PubMed Central

Venit, Tomáš; Dzijak, Rastislav; Kalendová, Alžběta; Kahle, Michal; Rohožková, Jana; Schmidt, Volker; Rülicke, Thomas; Rathkolb, Birgit; Hans, Wolfgang; Bohla, Alexander; Eickelberg, Oliver; Stoeger, Tobias; Wolf, Eckhard; Yildirim, Ali Önder; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabě; Hozák, Pavel

2013-01-01

Background Nuclear myosin I (NM1) is a nuclear isoform of the well-known “cytoplasmic” Myosin 1c protein (Myo1c). Located on the 11th chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. Methodology/Principal Findings In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. Conclusion/Significance We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes. PMID:23593477
Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

PubMed

Venit, Tomáš; Dzijak, Rastislav; Kalendová, Alžběta; Kahle, Michal; Rohožková, Jana; Schmidt, Volker; Rülicke, Thomas; Rathkolb, Birgit; Hans, Wolfgang; Bohla, Alexander; Eickelberg, Oliver; Stoeger, Tobias; Wolf, Eckhard; Yildirim, Ali Önder; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabě; Hozák, Pavel

2013-01-01

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes.
Computer-aided detection and quantification of endolymphatic hydrops within the mouse cochlea in vivo using optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, George S.; Kim, Jinkyung; Applegate, Brian E.; Oghalai, John S.

2017-07-01

Diseases that cause hearing loss and/or vertigo in humans such as Meniere's disease are often studied using animal models. The volume of endolymph within the inner ear varies with these diseases. Here, we used a mouse model of increased endolymph volume, endolymphatic hydrops, to develop a computer-aided objective approach to measure endolymph volume from images collected in vivo using optical coherence tomography. The displacement of Reissner's membrane from its normal position was measured in cochlear cross sections. We validated our computer-aided measurements with manual measurements and with trained observer labels. This approach allows for computer-aided detection of endolymphatic hydrops in mice, with test performance showing sensitivity of 91% and specificity of 87% using a running average of five measurements. These findings indicate that this approach is accurate and reliable for classifying endolymphatic hydrops and quantifying endolymph volume.

Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

PubMed

Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

2015-04-01

Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. Copyright © 2015 Elsevier Ltd. All rights reserved.
Peripheral and central auditory specialization in a gliding marsupial, the feathertail glider, Acrobates pygmaeus.

PubMed

Aitkin, L M; Nelson, J E

1989-01-01

Two specialized features are described in the auditory system of Acrobates pygmaeus, a small gliding marsupial. Firstly, the ear canal includes a transverse disk of bone that partly occludes the canal near the eardrum. The resultant narrow-necked chamber above the eardrum appears to attenuate sound across a broad frequency range, except at 27-29 kHz at which a net gain of sound pressure occurs. Secondly, the lateral medulla is hypertrophied at the level of the cochlear nucleus, forming a massive lateral lobe comprised of multipolar cells and granule cells. This lobe has connections with the auditory nerve and the cerebellum. Speculations are advanced about the functions of these structures in gliding behaviour and predator avoidance.
Vasopressin Innervation of the Mouse (Mus musculus) Brain and Spinal Cord

PubMed Central

Rood, Benjamin D.; De Vries, Geert J.

2014-01-01

The neuropeptide vasopressin (AVP) has been implicated in the regulation of numerous physiological and behavioral processes. Although mice have become an important model for studying this regulation, there is no comprehensive description of AVP distribution in the mouse brain and spinal cord. With C57BL/6 mice, we used immunohistochemistry to corroborate the location of AVP-containing cells and to define the location of AVP-containing fibers throughout the mouse central nervous system. We describe AVP-immunoreactive (-ir) fibers in midbrain, hindbrain, and spinal cord areas, which have not previously been reported in mice, including innervation of the ventral tegmental area, dorsal and median raphe, lateral and medial parabrachial, solitary, ventrolateral periaqueductal gray, and interfascicular nuclei. We also provide a detailed description of AVP-ir innervation in heterogenous regions such as the amygdala, bed nucleus of the stria terminalis, and ventral forebrain. In general, our results suggest that, compared with other species, the mouse has a particularly robust and widespread distribution of AVP-ir fibers, which, as in other species, originates from a number of different cell groups in the telencephalon and diencephalon. Our data also highlight the robust nature of AVP innervation in specific regulatory nuclei, such as the ventral tegmental area and dorsal raphe nucleus among others, that are implicated in the regulation of many behaviors. PMID:21456024
A conserved function for pericentromeric satellite DNA

PubMed Central

Jagannathan, Madhav; Cummings, Ryan

2018-01-01

A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here, we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus. We show that the multi-AT-hook satellite DNA-binding proteins, Drosophila melanogaster D1 and mouse HMGA1, play an evolutionarily conserved role in bundling pericentromeric satellite DNA from heterologous chromosomes into ‘chromocenters’, a cytological association of pericentromeric heterochromatin. Defective chromocenter formation leads to micronuclei formation due to budding from the interphase nucleus, DNA damage and cell death. We propose that chromocenter and satellite DNA serve a fundamental role in encapsulating the full complement of the genome within a single nucleus, the universal characteristic of eukaryotic cells. PMID:29578410
Apoptotic mechanisms after repeated noise trauma in the mouse medial geniculate body and primary auditory cortex.

PubMed

Fröhlich, Felix; Ernst, Arne; Strübing, Ira; Basta, Dietmar; Gröschel, Moritz

2017-12-01

A correlation between noise-induced apoptosis and cell loss has previously been shown after a single noise exposure in the cochlear nucleus, inferior colliculus, medial geniculate body (MGB) and primary auditory cortex (AI). However, repeated noise exposure is the most common situation in humans and a major risk factor for the induction of noise-induced hearing loss (NIHL). The present investigation measured cell death pathways using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the dorsal, medial and ventral MGB (dMGB, mMGB and vMGB) and six layers of the AI (AI-1 to AI-6) in mice (NMRI strain) after a second noise exposure (double-exposure group). Therefore, a single noise exposure group has been investigated 7 (7-day-group-single) or 14 days (14-day-group-single) after noise exposure (3 h, 5-20 kHz, 115 dB SPL peak-to-peak). The double-exposure group received the same noise trauma for a second time 7 days after the initial exposure and was either TUNEL-stained immediately (7-day-group-double) or 1 week later (14-day-group-double) and data were compared to the corresponding single-trauma group as well as to an unexposed control group. It was shown that TUNEL increased immediately after the second noise exposure in AI-3 and stayed upregulated in the 14-day-group-double. A significant increase in TUNEL was also seen in the 14-day-group-double in vMGB, mMGB and AI-1. The present results show for the first time the influence of a repeated noise trauma on cell death mechanisms in thalamic and cortical structures and might contribute to the understanding of pathophysiological findings and psychoacoustic phenomena accompanying NIHL.
Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

PubMed

Sengul, Gulgun; Puchalski, Ralph B; Watson, Charles

2012-05-01

Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord. Copyright © 2012 Wiley Periodicals, Inc.
Cochlear fluid space dimensions for six species derived from reconstructions of three-dimensional magnetic resonance images.

PubMed

Thorne, M; Salt, A N; DeMott, J E; Henson, M M; Henson, O W; Gewalt, S L

1999-10-01

To establish the dimensions and volumes of the cochlear fluid spaces. Fluid space volumes, lengths, and cross-sectional areas were derived for the cochleas from six species: human, guinea pig, bat, rat, mouse, and gerbil. Three-dimensional reconstructions of the fluid spaces were made from magnetic resonance microscopy (MRM) images. Consecutive serial slices composed of isotropic voxels (25 microm3) representing the entire volume of fixed, isolated cochleas were obtained. The boundaries delineating the fluid spaces, including Reissner's membrane, were resolved for all specimens, except for the human, in which Reissner's membrane was not consistently resolved. Three-dimensional reconstructions of the endolymphatic and perilymphatic fluid spaces were generated. Fluid space length and variation of cross-sectional area with distance were derived by an algorithm that followed the midpoint of the space along the length of the spiral. The total volume of each fluid space was derived from a voxel count for each specimen. Length, volume, and cross-sectional areas are provided for six species. In all cases, the length of the endolymphatic fluid space was consistently longer than that of either perilymphatic scala, primarily as a result of a greater radius of curvature. For guinea pig specimens, the measured volumes of the fluid spaces were considerably lower than those suggested by previous reports based on histological data. The quantification of cochlear fluid spaces provided by this study will enable the more accurate calculation of drug and other solute movements in fluids of the inner ear during experimental or clinical manipulations.
Scatter sensitive microscopic techniques to identify contrasting mucosal structures in ultrahigh-resolution optical coherence tomograms of mouse colon

NASA Astrophysics Data System (ADS)

Tumlinson, Alexandre R.; Hariri, Lida P.; Drexler, Wolfgang; Barton, Jennifer K.

2008-02-01

Optical coherence tomography, optical coherence microscopy, reflectance confocal microscopy, and darkfield microscopy all derive contrast from the intensity of endogenous tissue scatter. We have imaged excised mouse colon tissue with these complimentary technologies to make conclusions about structural origins of scatter in the mouse colonic mucosa observed with endoscopic OCT. We find hyperintense scattering both from the cytoplasm of epithelial cells and from the boundary between epithelia and the lamina propria. We find almost no scatter from the portion of epithelial cells containing the nucleus. These observations substantiate explanations for the appearance of colonic crypts and the luminal surface.
New Criteria of Indication and Selection of Patients to Cochlear Implant

PubMed Central

Sampaio, André L. L.; Araújo, Mercêdes F. S.; Oliveira, Carlos A. C. P.

2011-01-01

Numerous changes continue to occur in cochlear implant candidacy. In general, these have been accompanied by concomitant and satisfactory changes in surgical techniques. Together, this has advanced the utility and safety of cochlear implantation. Most devices are now approved for use in patients with severe to profound unilateral hearing loss rather then the prior requirement of a bilateral profound loss. Furthermore, studies have begun utilizing short electrode arrays for shallow insertion in patients with considerable low-frequency residual hearing. This technique will allow the recipient to continue to use acoustically amplified hearing for the low frequencies simultaneously with a cochlear implant for the high frequencies. The advances in design of, and indications for, cochlear implants have been matched by improvements in surgical techniques and decrease in complications. The resulting improvements in safety and efficacy have further encouraged the use of these devices. This paper will review the new concepts in the candidacy of cochlear implant. Medline data base was used to search articles dealing with the following topics: cochlear implant in younger children, cochlear implant and hearing preservation, cochlear implant for unilateral deafness and tinnitus, genetic hearing loss and cochlear implant, bilateral cochlear implant, neuropathy and cochlear implant and neural plasticity, and the selection of patients for cochlear implant. PMID:22013448
Hyperthermia combined with ethanol administration induces c-fos expression in the central amygdaloid nucleus of the mouse brain. A possible mechanism of heatstroke under the influence of ethanol intake.

PubMed

Kibayashi, Kazuhiko; Nakao, Ken-ichiro; Shojo, Hideki

2009-09-01

Heatstroke is defined as a core body temperature that rises above 40.6 degrees C and is accompanied by mental status abnormalities such as delirium, convulsions, or coma resulting from exposure to environmental heat. There is fairly wide agreement that ethanol intake is a predisposing factor in heatstroke. This study was performed to identify the brain changes induced by heatstroke, using a mouse hyperthermia model with and without preceding ethanol administration. Exposure to heat of 42 degrees C until the core temperature reached to 43 degrees C followed by exposure to 37 degrees C for 15 min decreased the levels of partial pressures of O(2) in blood. Preceding ethanol administration and heat exposure induced hypotension, severe metabolic acidosis and respiratory failure, and, accordingly, produced heatstroke. Immunohistochemistry of the brains showed that preceding ethanol administration increased the number of c-fos-immunoreactive neurons, as a marker of neuronal activation, in the central amygdaloid nucleus, which is involved in thermoregulation. These results indicate that combined effects of ethanol and heat exposure induce heatstroke that is associated with activation of the central amygdaloid nucleus, implicating the pathophysiology and mechanisms of heatstroke under the influence of ethanol intake.
ACF7 is a hair-bundle antecedent, positioned to integrate cuticular plate actin and somatic tubulin.

PubMed

Antonellis, Patrick J; Pollock, Lana M; Chou, Shih-Wei; Hassan, Ahmed; Geng, Ruishuang; Chen, Xi; Fuchs, Elaine; Alagramam, Kumar N; Auer, Manfred; McDermott, Brian M

2014-01-01

The precise morphology of the mechanosensitive hair bundle requires seamless integration of actin and microtubule networks. Here, we identify Acf7a (actin crosslinking family protein 7a) as a protein positioned to bridge these distinct cytoskeletal networks in hair cells. By imaging Acf7a-Citrine fusion protein in zebrafish and immunolabeling of vestibular and cochlear mouse hair cells, we show that Acf7a and ACF7 circumscribe, underlie, and are interwoven into the cuticular plate (CP), and they also encircle the basal body of the kinocilium. In cochlear hair cells, ACF7 localization is graded, with the highest concentration near each fonticulus--an area free of F-actin in the region of the CP that contains the basal body. During hair-cell development and regeneration, Acf7a precedes formation of the hair bundle and CP. Finally, electron tomography demonstrates that the ends of microtubules insert into the CP and are decorated with filamentous linkers connecting microtubules to the CP. These observations are consistent with ACF7 being a linker protein, which may shape the cytoskeleton of the hair cell early during hair-bundle genesis.
ACF7 Is a Hair-Bundle Antecedent, Positioned to Integrate Cuticular Plate Actin and Somatic Tubulin

PubMed Central

Antonellis, Patrick J.; Pollock, Lana M.; Chou, Shih-Wei; Hassan, Ahmed; Geng, Ruishuang; Chen, Xi; Fuchs, Elaine; Alagramam, Kumar N.; Auer, Manfred

2014-01-01

The precise morphology of the mechanosensitive hair bundle requires seamless integration of actin and microtubule networks. Here, we identify Acf7a (actin crosslinking family protein 7a) as a protein positioned to bridge these distinct cytoskeletal networks in hair cells. By imaging Acf7a–Citrine fusion protein in zebrafish and immunolabeling of vestibular and cochlear mouse hair cells, we show that Acf7a and ACF7 circumscribe, underlie, and are interwoven into the cuticular plate (CP), and they also encircle the basal body of the kinocilium. In cochlear hair cells, ACF7 localization is graded, with the highest concentration near each fonticulus—an area free of F-actin in the region of the CP that contains the basal body. During hair-cell development and regeneration, Acf7a precedes formation of the hair bundle and CP. Finally, electron tomography demonstrates that the ends of microtubules insert into the CP and are decorated with filamentous linkers connecting microtubules to the CP. These observations are consistent with ACF7 being a linker protein, which may shape the cytoskeleton of the hair cell early during hair-bundle genesis. PMID:24381291
Deletion of SLC19A2, the high affinity thiamine transporter, causes selective inner hair cell loss and an auditory neuropathy phenotype.

PubMed

Liberman, M C; Tartaglini, E; Fleming, J C; Neufeld, E J

2006-09-01

Mutations in the gene coding for the high-affinity thiamine transporter Slc19a2 underlie the clinical syndrome known as thiamine-responsive megaloblastic anemia (TRMA) characterized by anemia, diabetes, and sensorineural hearing loss. To create a mouse model of this disease, a mutant line was created with targeted disruption of the gene. Cochlear function is normal in these mutants when maintained on a high-thiamine diet. When challenged with a low-thiamine diet, Slc19a2-null mice showed 40-60 dB threshold elevations by auditory brainstem response (ABR), but only 10-20 dB elevation by otoacoustic emission (OAE) measures. Wild-type mice retain normal hearing on either diet. Cochlear histological analysis showed a pattern uncommon for sensorineural hearing loss: selective loss of inner hair cells after 1-2 weeks on low thiamine and significantly greater inner than outer hair cell loss after longer low-thiamine challenges. Such a pattern is consistent with the observed discrepancy between ABR and OAE threshold shifts. The possible role of thiamine transport in other reported cases of selective inner hair cell loss is considered.
Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death

PubMed Central

Kenyon, Emma J.; Kirkwood, Nerissa K.; Kitcher, Siân R.; O’Reilly, Molly; Cantillon, Daire M.; Goodyear, Richard J.; Secker, Abigail; Baxendale, Sarah; Bull, James C.; Waddell, Simon J.; Whitfield, Tanya T.; Ward, Simon E.; Kros, Corné J.; Richardson, Guy P.

2017-01-01

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red–conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem. PMID:29263311
Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

PubMed Central

McLean, Will J.; McLean, Dalton T.; Eatock, Ruth Anne

2016-01-01

Disorders of hearing and balance are most commonly associated with damage to cochlear and vestibular hair cells or neurons. Although these cells are not capable of spontaneous regeneration, progenitor cells in the hearing and balance organs of the neonatal mammalian inner ear have the capacity to generate new hair cells after damage. To investigate whether these cells are restricted in their differentiation capacity, we assessed the phenotypes of differentiated progenitor cells isolated from three compartments of the mouse inner ear – the vestibular and cochlear sensory epithelia and the spiral ganglion – by measuring electrophysiological properties and gene expression. Lgr5+ progenitor cells from the sensory epithelia gave rise to hair cell-like cells, but not neurons or glial cells. Newly created hair cell-like cells had hair bundle proteins, synaptic proteins and membrane proteins characteristic of the compartment of origin. PLP1+ glial cells from the spiral ganglion were identified as neural progenitors, which gave rise to neurons, astrocytes and oligodendrocytes, but not hair cells. Thus, distinct progenitor populations from the neonatal inner ear differentiate to cell types associated with their organ of origin. PMID:27789624
The expression of PTEN in the development of mouse cochlear lateral wall.

PubMed

Dong, Y; Sui, L; Yamaguchi, F; Kamitori, K; Hirata, Y; Hossain, A; Noguchi, C; Katagi, A; Nishio, M; Suzuki, A; Lou, X; Tokuda, M

2014-01-31

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that regulates various cell processes including proliferation, growth, synaptogenesis, neural and glioma stem/progenitor cell renewal. In addition, PTEN can regulate sensory cell proliferation and differentiation of hair bundles in the mammalian cochlea. In this study we use immunofluorescence, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) to reveal the expression of PTEN in the developing cochlear lateral wall, which is crucial for regulating K(+) homeostasis. Relatively high levels of PTEN are initially expressed in the marginal cells (MCs) of the lateral wall at embryonic day (E) 17.5 when they start to differentiate. Similarly high levels are subsequently expressed in differentiating root cells (RCs) at postnatal day (P) 3 and then in spiral ligament fibrocytes (SLFs) at P 10. In the mature cochlea, PTEN expression is low or undetectable in MCs and SLFs but it remains high in RCs and their processes. The expression pattern for PTEN in the developing lateral wall suggests that it plays a critical role in the differentiation of the cellular pathways that regulate K(+) homeostasis in the cochlea. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing.

PubMed

Vogl, Christian; Butola, Tanvi; Haag, Natja; Hausrat, Torben J; Leitner, Michael G; Moutschen, Michel; Lefèbvre, Philippe P; Speckmann, Carsten; Garrett, Lillian; Becker, Lore; Fuchs, Helmut; Hrabe de Angelis, Martin; Nietzsche, Sandor; Kessels, Michael M; Oliver, Dominik; Kneussel, Matthias; Kilimann, Manfred W; Strenzke, Nicola

2017-11-01

Lipopolysaccharide-responsive beige-like anchor protein (LRBA) belongs to the enigmatic class of BEACH domain-containing proteins, which have been attributed various cellular functions, typically involving intracellular protein and membrane transport processes. Here, we show that LRBA deficiency in mice leads to progressive sensorineural hearing loss. In LRBA knockout mice, inner and outer hair cell stereociliary bundles initially develop normally, but then partially degenerate during the second postnatal week. LRBA deficiency is associated with a reduced abundance of radixin and Nherf2, two adaptor proteins, which are important for the mechanical stability of the basal taper region of stereocilia. Our data suggest that due to the loss of structural integrity of the central parts of the hair bundle, the hair cell receptor potential is reduced, resulting in a loss of cochlear sensitivity and functional loss of the fraction of spiral ganglion neurons with low spontaneous firing rates. Clinical data obtained from two human patients with protein-truncating nonsense or frameshift mutations suggest that LRBA deficiency may likewise cause syndromic sensorineural hearing impairment in humans, albeit less severe than in our mouse model. © 2017 The Authors.
Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death.

PubMed

Kenyon, Emma J; Kirkwood, Nerissa K; Kitcher, Siân R; O'Reilly, Molly; Derudas, Marco; Cantillon, Daire M; Goodyear, Richard J; Secker, Abigail; Baxendale, Sarah; Bull, James C; Waddell, Simon J; Whitfield, Tanya T; Ward, Simon E; Kros, Corné J; Richardson, Guy P

2017-12-21

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red-conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem.
Silent Damage of Noise on Cochlear Afferent Innervation in Guinea Pigs and the Impact on Temporal Processing

PubMed Central

He, Tingting; Aiken, Steve; Bance, Manohar; Yin, Shankai; Wang, Jian

2012-01-01

Noise-exposure at levels low enough to avoid a permanent threshold shift has been found to cause a massive, delayed degeneration of spiral ganglion neurons (SGNs) in mouse cochleae. Damage to the afferent innervation was initiated by a loss of synaptic ribbons, which is largely irreversible in mice. A similar delayed loss of SGNs has been found in guinea pig cochleae, but at a reduced level, suggesting a cross-species difference in SGN sensitivity to noise. Ribbon synapse damage occurs “silently” in that it does not affect hearing thresholds as conventionally measured, and the functional consequence of this damage is not clear. In the present study, we further explored the effect of noise on cochlear afferent innervation in guinea pigs by focusing on the dynamic changes in ribbon counts over time, and resultant changes in temporal processing. It was found that (1) contrary to reports in mice, the initial loss of ribbons largely recovered within a month after the noise exposure, although a significant amount of residual damage existed; (2) while the response threshold fully recovered in a month, the temporal processing continued to be deteriorated during this period. PMID:23185359
Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

PubMed

Carter, D A; Choong, Y-T; Connelly, A A; Bassi, J K; Hunter, N O; Thongsepee, N; Llewellyn-Smith, I J; Fong, A Y; McDougall, S J; Allen, A M

2017-10-01

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT 1A R) most widely expressed in adult neurons. Activation of the AT 1 R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT 1 R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT 1A R-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT 1A R promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT 1A R-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT 1A R-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT 1A R-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT 1A R-GFP neurons and TH-GFP neurons showed similar AT 1A R-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT 1A R-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing. Copyright © 2017 the American Physiological Society.

Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) but not PPAR-interacting protein (PRIP) is required for nuclear translocation of constitutive androstane receptor in mouse liver.

PubMed

Guo, Dongsheng; Sarkar, Joy; Ahmed, Mohamed R; Viswakarma, Navin; Jia, Yuzhi; Yu, Songtao; Sambasiva Rao, M; Reddy, Janardan K

2006-08-25

The constitutive androstane receptor (CAR) regulates transcription of phenobarbital-inducible genes that encode xenobiotic-metabolizing enzymes in liver. CAR is localized to the hepatocyte cytoplasm but to be functional, it translocates into the nucleus in the presence of phenobarbital-like CAR ligands. We now demonstrate that adenovirally driven EGFP-CAR, as expected, translocates into the nucleus of normal wild-type hepatocytes following phenobarbital treatment under both in vivo and in vitro conditions. Using this approach we investigated the role of transcription coactivators PBP and PRIP in the translocation of EGFP-CAR into the nucleus of PBP and PRIP liver conditional null mouse hepatocytes. We show that coactivator PBP is essential for nuclear translocation of CAR but not PRIP. Adenoviral expression of both PBP and EGFP-CAR restored phenobarbital-mediated nuclear translocation of exogenously expressed CAR in PBP null livers in vivo and in PBP null primary hepatocytes in vitro. CAR translocation into the nucleus of PRIP null livers resulted in the induction of CAR target genes such as CYP2B10, necessary for the conversion of acetaminophen to its hepatotoxic intermediate metabolite, N-acetyl-p-benzoquinone imine. As a consequence, PRIP-deficiency in liver did not protect from acetaminophen-induced hepatic necrosis, unlike that exerted by PBP deficiency. These results establish that transcription coactivator PBP plays a pivotal role in nuclear localization of CAR, that it is likely that PBP either enhances nuclear import or nuclear retention of CAR in hepatocytes, and that PRIP is redundant for CAR function.
Pharmacological and immunochemical characterization of α2* nicotinic acetylcholine receptors (nAChRs) in mouse brain

PubMed Central

Whiteaker, Paul; Wilking, Jennifer A; Brown, Robert WB; Brennan, Robert J; Collins, Allan C; Lindstrom, Jon M; Boulter, Jim

2009-01-01

Aim: α2 nAChR subunit mRNA expression in mice is most intense in the olfactory bulbs and interpeduncular nucleus. We aimed to investigate the properties of α2* nAChRs in these mouse brain regions. Methods: α2 nAChR subunit-null mutant mice were engineered. Pharmacological and immunoprecipitation studies were used to determine the composition of α2 subunit-containing (α2*) nAChRs in these two regions. Results: [125I]Epibatidine (200 pmol/L) autoradiography and saturation binding demonstrated that α2 deletion reduces nAChR expression in both olfactory bulbs and interpeduncular nucleus (by 4.8±1.7 and 92±26 fmol̇mg-1 protein, respectively). Pharmacological characterization using the β2-selective drug A85380 to inhibit [125I]epibatidine binding proved inconclusive, so immunoprecipitation methods were used to further characterize α2* nAChRs. Protocols were established to immunoprecipitate β2 and β4 nAChRs. Immunoprecipitation specificity was ascertained using tissue from β2- and β4-null mutant mice, and efficacy was good (>90% of β2* and >80% of β4* nAChRs were routinely recovered). Conclusion: Immunoprecipitation experiments indicated that interpeduncular nucleus α2* nAChRs predominantly contain β2 subunits, while those in olfactory bulbs contain mainly β4 subunits. In addition, the immunoprecipitation evidence indicated that both nuclei, but especially the interpeduncular nucleus, express nAChR complexes containing both β2 and β4 subunits. PMID:19498420
Fitting recommendations and clinical benefit associated with use of the NAL-NL2 hearing-aid prescription in Nucleus cochlear implant recipients.

PubMed

English, Ruth; Plant, Kerrie; Maciejczyk, Michael; Cowan, Robert

2016-01-01

For a group of cochlear implant recipients, who use hearing aids in the contralateral ear, the benefit of NAL-NL2 relative to a recipients' own prescription was assessed. Whether there was a preferred frequency response and/or gain deviation from NAL-NL2 was then investigated. Speech recognition and self-reported ratings of benefit were examined for the recipients' own prescription compared to the NAL-NL2 prescription, in the bimodal and hearing-aid alone conditions. Paired-comparison of hearing-aid frequency response was conducted with default NAL-NL2 and two variants, a low frequency boost or cut. Using a loudness balancing procedure, the hearing-aid gain required to achieve equal loudness between the devices was measured. Sixteen adults with post-lingual hearing loss. A 22% increase in group median word score in quiet with use of NAL-NL2 in the hearing-aid alone condition. In the bimodal condition there was no improvement with NAL-NL2. Default NAL-NL2 frequency response was preferred by 67% of participants. For 56% of participants, the preferred gain to achieve loudness balance across bimodal devices was within 5-dB of prescribed values. The NAL-NL2 prescription provides a high level of clinical performance, and an acceptable frequency response and gain for most participants.
MRI evidence of endolymphatic impermeability to the gadolinium molecule in the in vivo mouse inner ear at 9.4 tesla.

PubMed

Counter, S Allen; Nikkhou, Sahar; Brené, Stefan; Damberg, Peter; Sierakowiak, Adam; Klason, Tomas; Berglin, Cecilia Engmér; Laurell, Göran

2013-01-01

Previous in vivo experimental magnetic resonance imaging (MRI) investigations of the mammalian inner ear at 4.7 Tesla have indicated that intravenously injected gadolinium (Gd) penetrates the perilymphatic labyrinth, but not the endolymphatic membranous labyrinth. In the present study, high field MRI at 9.4T was used to visualize the in vivo mouse vestibulo-cochlea system, and to determine whether the endolymphatic system is permeable to a Gd complex. A 9.4 T Varian magnet equipped with a 12 cm inner diameter gradient system with maximum gradient strength of 600 mT/m, a millipede coil (Varian design) and a Gd contrast agent were used for image acquisition in the normal C57 BL-6 mouse. High-resolution 2D and 3D images of the mouse cochlea were acquired within 80 minutes following intravenous injection of Gd. Gd initially permeated the perilymphatic scala tympani and scala vestibuli, and permitted visualization of both cochlear turns from base to apex. The superior, inferior and lateral semicircular canals were subsequently visualized in 3 planes. The membranous endolymphatic labyrinth was impermeable to intravenously injected Gd, and thus showed no apparent uptake of Gd at 9.4T. The 9.4T field strength MRI permitted acquisition of high resolution images of anatomical and physiological features of the normal, wild type mouse perilymphatic inner ear in vivo, and provided further evidence that the endolymphatic system is impermeable to intravenously injected Gd.
Characterization of a novel binding partner of the melanocortin-4 receptor: attractin-like protein.

PubMed Central

Haqq, Andrea M; René, Patricia; Kishi, Toshiro; Khong, Kathy; Lee, Charlotte E; Liu, Hongyan; Friedman, Jeffrey M; Elmquist, Joel K; Cone, Roger D

2003-01-01

The gene dosage effect of the MC4-R (melanocortin 4 receptor) on obesity suggests that regulation of MC4-R expression and function is critically important to the central control of energy homoeostasis. In order to identify putative MC4-R regulatory proteins, we performed a yeast two-hybrid screen of a mouse brain cDNA library using the mouse MC4-R intracellular tail (residues 303-332) as bait. We report here on one positive clone that shares 63% amino acid identity with the C-terminal part of the mouse attractin gene product, a single-transmembrane-domain protein characterized as being required for agouti signalling through the melanocortin 1 receptor. We confirmed a direct interaction between this ALP (attractin-like protein) and the C-terminus of the mouse MC4-R by glutathione S-transferase pulldown experiments, and mapped the regions involved in this interaction using N- and C-terminal truncation constructs; residues 303-313 in MC4-R and residues 1280-1317 in ALP are required for binding. ALP is highly expressed in brain, but also in heart, lung, kidney and liver. Furthermore, co-localization analyses in mice showed co-expression of ALP in cells expressing MC4-R in a number of regions known to be important in the regulation of energy homoeostasis by melanocortins, such as the paraventricular nucleus of hypothalamus and the dorsal motor nucleus of the vagus. PMID:14531729
Circadian Timing in the Lung; A Specific Role for Bronchiolar Epithelial Cells

PubMed Central

Gibbs, J. E.; Beesley, S.; Plumb, J.; Singh, D.; Farrow, S.; Ray, D. W.; Loudon, A. S. I.

2015-01-01

In addition to the core circadian oscillator, located within the suprachiasmatic nucleus, numerous peripheral tissues possess self-sustaining circadian timers. In vivo these are entrained and temporally synchronized by signals conveyed from the core oscillator. In the present study, we examine circadian timing in the lung, determine the cellular localization of core clock proteins in both mouse and human lung tissue, and establish the effects of glucocorticoids (widely used in the treatment of asthma) on the pulmonary clock. Using organotypic lung slices prepared from transgenic mPER2::Luc mice, luciferase levels, which report PER2 expression, were measured over a number of days. We demonstrate a robust circadian rhythm in the mouse lung that is responsive to glucocorticoids. Immunohistochemical techniques were used to localize specific expression of core clock proteins, and the glucocorticoid receptor, to the epithelial cells lining the bronchioles in both mouse and human lung. In the mouse, these were established to be Clara cells. Murine Clara cells retained circadian rhythmicity when grown as a pure population in culture. Furthermore, selective ablation of Clara cells resulted in the loss of circadian rhythm in lung slices, demonstrating the importance of this cell type in maintaining overall pulmonary circadian rhythmicity. In summary, we demonstrate that Clara cells are critical for maintaining coherent circadian oscillations in lung tissue. Their coexpression of the glucocorticoid receptor and core clock components establishes them as a likely interface between humoral suprachiasmatic nucleus output and circadian lung physiology. PMID:18787022
fMRI as a Preimplant Objective Tool to Predict Children's Postimplant Auditory and Language Outcomes as Measured by Parental Observations.

PubMed

Deshpande, Aniruddha K; Tan, Lirong; Lu, Long J; Altaye, Mekibib; Holland, Scott K

2018-05-01

The trends in cochlear implantation candidacy and benefit have changed rapidly in the last two decades. It is now widely accepted that early implantation leads to better postimplant outcomes. Although some generalizations can be made about postimplant auditory and language performance, neural mechanisms need to be studied to predict individual prognosis. The aim of this study was to use functional magnetic resonance imaging (fMRI) to identify preimplant neuroimaging biomarkers that predict children's postimplant auditory and language outcomes as measured by parental observation/reports. This is a pre-post correlational measures study. Twelve possible cochlear implant candidates with bilateral severe to profound hearing loss were recruited via referrals for a clinical magnetic resonance imaging to ensure structural integrity of the auditory nerve for implantation. Participants underwent cochlear implantation at a mean age of 19.4 mo. All children used the advanced combination encoder strategy (ACE, Cochlear Corporation™, Nucleus ® Freedom cochlear implants). Three participants received an implant in the right ear; one in the left ear whereas eight participants received bilateral implants. Participants' preimplant neuronal activation in response to two auditory stimuli was studied using an event-related fMRI method. Blood oxygen level dependent contrast maps were calculated for speech and noise stimuli. The general linear model was used to create z-maps. The Auditory Skills Checklist (ASC) and the SKI-HI Language Development Scale (SKI-HI LDS) were administered to the parents 2 yr after implantation. A nonparametric correlation analysis was implemented between preimplant fMRI activation and postimplant auditory and language outcomes based on ASC and SKI-HI LDS. Statistical Parametric Mapping software was used to create regression maps between fMRI activation and scores on the aforementioned tests. Regression maps were overlaid on the Imaging Research Center infant template and visualized in MRIcro. Regression maps revealed two clusters of brain activation for the speech versus silence contrast and five clusters for the noise versus silence contrast that were significantly correlated with the parental reports. These clusters included auditory and extra-auditory regions such as the middle temporal gyrus, supramarginal gyrus, precuneus, cingulate gyrus, middle frontal gyrus, subgyral, and middle occipital gyrus. Both positive and negative correlations were observed. Correlation values for the different clusters ranged from -0.90 to 0.95 and were significant at a corrected p value of <0.05. Correlations suggest that postimplant performance may be predicted by activation in specific brain regions. The results of the present study suggest that (1) fMRI can be used to identify neuroimaging biomarkers of auditory and language performance before implantation and (2) activation in certain brain regions may be predictive of postimplant auditory and language performance as measured by parental observation/reports. American Academy of Audiology.
Cardioprotection induced in a mouse model of neuropathic pain via anterior nucleus of paraventricular thalamus.

PubMed

Cheng, Yi-Fen; Chang, Ya-Ting; Chen, Wei-Hsin; Shih, Hsi-Chien; Chen, Yen-Hui; Shyu, Bai-Chuang; Chen, Chien-Chang

2017-10-10

Myocardial infarction is the leading cause of death worldwide. Restoration of blood flow rescues myocardium but also causes ischemia-reperfusion injury. Here, we show that in a mouse model of chronic neuropathic pain, ischemia-reperfusion injury following myocardial infarction is reduced, and this cardioprotection is induced via an anterior nucleus of paraventricular thalamus (PVA)-dependent parasympathetic pathway. Pharmacological inhibition of extracellular signal-regulated kinase activation in the PVA abolishes neuropathic pain-induced cardioprotection, whereas activation of PVA neurons pharmacologically, or optogenetic stimulation, is sufficient to induce cardioprotection. Furthermore, neuropathic injury and optogenetic stimulation of PVA neurons reduce the heart rate. These results suggest that the parasympathetic nerve is responsible for this unexpected cardioprotective effect of chronic neuropathic pain in mice.Various forms of preconditioning can prevent ischemic-reperfusion injury after myocardial infarction. Here, the authors show that in mice, the presence of chronic neuropathic pain can have a cardioprotective effect, and that this is dependent on neural activation in the paraventricular thalamus.
Cochlear Implants.

ERIC Educational Resources Information Center

Clark, Catherine; Scott, Larry

This brochure explains what a cochlear implant is, lists the types of individuals with deafness who may be helped by a cochlear implant, describes the process of evaluating people for cochlear implants, discusses the surgical process for implanting the aid, traces the path of sound through the cochlear implant to the brain, notes the costs of…
Terminations of reticulospinal fibers originating from the gigantocellular reticular formation in the mouse spinal cord.

PubMed

Liang, Huazheng; Watson, Charles; Paxinos, George

2016-04-01

The present study investigated the projections of the gigantocellular reticular nucleus (Gi) and its neighbors--the dorsal paragigantocellular reticular nucleus (DPGi), the alpha/ventral part of the gigantocellular reticular nucleus (GiA/V), and the lateral paragigantocellular reticular nucleus (LPGi)--to the mouse spinal cord by injecting the anterograde tracer biotinylated dextran amine (BDA) into the Gi, DPGi, GiA/GiV, and LPGi. The Gi projected to the entire spinal cord bilaterally with an ipsilateral predominance. Its fibers traveled in both the ventral and lateral funiculi with a greater presence in the ventral funiculus. As the fibers descended in the spinal cord, their density in the lateral funiculus increased. The terminals were present mainly in laminae 7-10 with a dorsolateral expansion caudally. In the lumbar and sacral cord, a considerable number of terminals were also present in laminae 5 and 6. Contralateral fibers shared a similar pattern to their ipsilateral counterparts and some fibers were seen to cross the midline. Fibers arising from the DPGi were similarly distributed in the spinal cord except that there was no dorsolateral expansion in the lumbar and sacral segments and there were fewer fiber terminals. Fibers arising from GiA/V predominantly traveled in the ventral and lateral funiculi ipsilaterally. Ipsilaterally, the density of fibers in the ventral funiculus decreased along the rostrocaudal axis, whereas the density of fibers in the lateral funiculus increased. They terminate mainly in the medial ventral horn and lamina 10 with a smaller number of fibers in the dorsal horn. Fibers arising from the LPGi traveled in both the ventral and lateral funiculi and the density of these fibers in the ventral and lateral funiculi decreased dramatically in the lumbar and sacral segments. Their terminals were present in the ventral horn with a large portion of them terminating in the motor neuron columns. The present study is the first demonstration of the termination pattern of fibers arising from the Gi, DPGi, GiA/GiV, and LPGi in the mouse spinal cord. It provides an anatomical foundation for those who are conducting spinal cord injury and locomotion related research.
Optimization of programming parameters in children with the advanced bionics cochlear implant.

PubMed

Baudhuin, Jacquelyn; Cadieux, Jamie; Firszt, Jill B; Reeder, Ruth M; Maxson, Jerrica L

2012-05-01

Cochlear implants provide access to soft intensity sounds and therefore improved audibility for children with severe-to-profound hearing loss. Speech processor programming parameters, such as threshold (or T-level), input dynamic range (IDR), and microphone sensitivity, contribute to the recipient's program and influence audibility. When soundfield thresholds obtained through the speech processor are elevated, programming parameters can be modified to improve soft sound detection. Adult recipients show improved detection for low-level sounds when T-levels are set at raised levels and show better speech understanding in quiet when wider IDRs are used. Little is known about the effects of parameter settings on detection and speech recognition in children using today's cochlear implant technology. The overall study aim was to assess optimal T-level, IDR, and sensitivity settings in pediatric recipients of the Advanced Bionics cochlear implant. Two experiments were conducted. Experiment 1 examined the effects of two T-level settings on soundfield thresholds and detection of the Ling 6 sounds. One program set T-levels at 10% of most comfortable levels (M-levels) and another at 10 current units (CUs) below the level judged as "soft." Experiment 2 examined the effects of IDR and sensitivity settings on speech recognition in quiet and noise. Participants were 11 children 7-17 yr of age (mean 11.3) implanted with the Advanced Bionics High Resolution 90K or CII cochlear implant system who had speech recognition scores of 20% or greater on a monosyllabic word test. Two T-level programs were compared for detection of the Ling sounds and frequency modulated (FM) tones. Differing IDR/sensitivity programs (50/0, 50/10, 70/0, 70/10) were compared using Ling and FM tone detection thresholds, CNC (consonant-vowel nucleus-consonant) words at 50 dB SPL, and Hearing in Noise Test for Children (HINT-C) sentences at 65 dB SPL in the presence of four-talker babble (+8 signal-to-noise ratio). Outcomes were analyzed using a paired t-test and a mixed-model repeated measures analysis of variance (ANOVA). T-levels set 10 CUs below "soft" resulted in significantly lower detection thresholds for all six Ling sounds and FM tones at 250, 1000, 3000, 4000, and 6000 Hz. When comparing programs differing by IDR and sensitivity, a 50 dB IDR with a 0 sensitivity setting showed significantly poorer thresholds for low frequency FM tones and voiced Ling sounds. Analysis of group mean scores for CNC words in quiet or HINT-C sentences in noise indicated no significant differences across IDR/sensitivity settings. Individual data, however, showed significant differences between IDR/sensitivity programs in noise; the optimal program differed across participants. In pediatric recipients of the Advanced Bionics cochlear implant device, manually setting T-levels with ascending loudness judgments should be considered when possible or when low-level sounds are inaudible. Study findings confirm the need to determine program settings on an individual basis as well as the importance of speech recognition verification measures in both quiet and noise. Clinical guidelines are suggested for selection of programming parameters in both young and older children. American Academy of Audiology.
Early postnatal virus inoculation into the scala media achieved extensive expression of exogenous green fluorescent protein in the inner ear and preserved auditory brainstem response thresholds.

PubMed

Wang, Yunfeng; Sun, Yu; Chang, Qing; Ahmad, Shoeb; Zhou, Binfei; Kim, Yeunjung; Li, Huawei; Lin, Xi

2013-01-01

Gene transfer into the inner ear is a promising approach for treating sensorineural hearing loss. The special electrochemical environment of the scala media raises a formidable challenge for effective gene delivery at the same time as keeping normal cochlear function intact. The present study aimed to define a suitable strategy for preserving hearing after viral inoculation directly into the scala media performed at various postnatal developmental stages. We assessed transgene expression of green fluorescent protein (GFP) mediated by various types of adeno-associated virus (AAV) and lentivirus (LV) in the mouse cochlea. Auditory brainstem responses were measured 30 days after inoculation to assess effects on hearing. Patterns of GFP expression confirmed extensive exogenous gene expression in various types of cells lining the endolymphatic space. The use of different viral vectors and promoters resulted in specific cellular GFP expression patterns. AAV2/1 with cytomegalovirus promoter apparently gave the best results for GFP expression in the supporting cells. Histological examination showed normal cochlear morphology and no hair cell loss after either AAV or LV injections. We found that hearing thresholds were not significantly changed when the injections were performed in mice younger than postnatal day 5, regardless of the type of virus tested. Viral inoculation and expression in the inner ear for the restoration of hearing must not damage cochlear function. Using normal hearing mice as a model, we have achieved this necessary step, which is required for the treatment of many types of congenital deafness that require early intervention. Copyright © 2013 John Wiley & Sons, Ltd.
Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.

PubMed

Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni

2017-09-01

CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [ 3 H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal levels of DOPET. At the same concentration, 0.1μM, CART (55-102) peptide did not have any effect on the release of noradrenaline. In the presence of CART (55-102) peptide, 0.1μM, the effect of cocaine, 30μM, on the basal dopamine release was inhibited and the effect on the basal DOPAC release substantially increased. To our knowledge, our findings are the first to show direct neurochemical evidence that CART (55-102) peptide plays a neuromodulatory role on the dopaminergic reward system by decreasing dopamine in the mouse nucleus accumbens and by attenuating cocaine-induced effects on dopamine release. Copyright © 2017 Elsevier Inc. All rights reserved.
[Inspecting the cochlear scala tympanic with flexible and semi-flexible micro-endoscope].

PubMed

Zhang, Daoxcing; Zhang, Yankun

2006-02-01

Flexible and semi-flexible micro-endoscopes were used in cochlear scala tympani inspection , to explore their application in inner ear examination. Fifteen profound hearing loss patients preparing for cochlear implant were included in this study. During the operation, micro-endoscopy was performed after opening the cochlear scala tympani. And 1 mm diameter semi-flexible micro-endoscope could go as deep as 9 mm into the cochlear scala tympani, while 0. 5 mm diameter flexible micro-endoscope could go as deep as 25 mm. The inspecting results were compared with video recording. Using 0.5 mm flexible micro-endoscope, we canould check cochlear scala tympani with depth range of 15-25 mm, but the video imaging was not clear enough to examine the microstructure in the cochlear. With 1 mm diameter semi-flexible micro-endoscope, we could reach 9 mm deep into the cochlear. During the examination, we found 3 cases with calcification deposit in osseous spiral lamina, l case with granulation tissue in the lateral wall of scala tympani, no abnormal findings in the other 11 cases. Inspecting the cochlear scala tympani with 0.5 mm flexible micro-endoscope, even though we can reach the second circuit of the cochlear, it is difficult to find the pathology in the cochlear because of the poor video imaging. With 1 mm semi-flexible micro-endoscope, we can identify the microstructure of the cochlear clearly and find the pathologic changes, but the inserting depth was limited to 9 mm with limitation to examine the whole cochlear.
What Does Music Sound Like for a Cochlear Implant User?

PubMed

Jiam, Nicole T; Caldwell, Meredith T; Limb, Charles J

2017-09-01

Cochlear implant research and product development over the past 40 years have been heavily focused on speech comprehension with little emphasis on music listening and enjoyment. The relatively little understanding of how music sounds in a cochlear implant user stands in stark contrast to the overall degree of importance the public places on music and quality of life. The purpose of this article is to describe what music sounds like to cochlear implant users, using a combination of existing research studies and listener descriptions. We examined the published literature on music perception in cochlear implant users, particularly postlingual cochlear implant users, with an emphasis on the primary elements of music and recorded music. Additionally, we administered an informal survey to cochlear implant users to gather first-hand descriptions of music listening experience and satisfaction from the cochlear implant population. Limitations in cochlear implant technology lead to a music listening experience that is significantly distorted compared with that of normal hearing listeners. On the basis of many studies and sources, we describe how music is frequently perceived as out-of-tune, dissonant, indistinct, emotionless, and weak in bass frequencies, especially for postlingual cochlear implant users-which may in part explain why music enjoyment and participation levels are lower after implantation. Additionally, cochlear implant users report difficulty in specific musical contexts based on factors including but not limited to genre, presence of lyrics, timbres (woodwinds, brass, instrument families), and complexity of the perceived music. Future research and cochlear implant development should target these areas as parameters for improvement in cochlear implant-mediated music perception.
Differentiation of Mouse Induced Pluripotent Stem Cells (iPSCs) into Nucleus Pulposus-Like Cells In Vitro

PubMed Central

Chen, Jun; Lee, Esther J.; Jing, Liufang; Christoforou, Nicolas; Leong, Kam W.; Setton, Lori A.

2013-01-01

A large percentage of the population may be expected to experience painful symptoms or disability associated with intervertebral disc (IVD) degeneration – a condition characterized by diminished integrity of tissue components. Great interest exists in the use of autologous or allogeneic cells delivered to the degenerated IVD to promote matrix regeneration. Induced pluripotent stem cells (iPSCs), derived from a patient’s own somatic cells, have demonstrated their capacity to differentiate into various cell types although their potential to differentiate into an IVD cell has not yet been demonstrated. The overall objective of this study was to assess the possibility of generating iPSC-derived nucleus pulposus (NP) cells in a mouse model, a cell population that is entirely derived from notochord. This study employed magnetic activated cell sorting (MACS) to isolate a CD24+ iPSC subpopulation. Notochordal cell-related gene expression was analyzed in this CD24+ cell fraction via real time RT-PCR. CD24+ iPSCs were then cultured in a laminin-rich culture system for up to 28 days, and the mouse NP phenotype was assessed by immunostaining. This study also focused on producing a more conducive environment for NP differentiation of mouse iPSCs with addition of low oxygen tension and notochordal cell conditioned medium (NCCM) to the culture platform. iPSCs were evaluated for an ability to adopt an NP-like phenotype through a combination of immunostaining and biochemical assays. Results demonstrated that a CD24+ fraction of mouse iPSCs could be retrieved and differentiated into a population that could synthesize matrix components similar to that in native NP. Likewise, the addition of a hypoxic environment and NCCM induced a similar phenotypic result. In conclusion, this study suggests that mouse iPSCs have the potential to differentiate into NP-like cells and suggests the possibility that they may be used as a novel cell source for cellular therapy in the IVD. PMID:24086564
Functional Fast Scan Cyclic Voltammetry Assay to Characterize Dopamine D2 and D3 Autoreceptors in the Mouse Striatum

PubMed Central

2010-01-01

Dopamine D2 and D3 autoreceptors are located on presynaptic terminals and are known to control the release and synthesis of dopamine. Dopamine D3 receptors have a fairly restricted pattern of expression in the mammalian brain. Their localization in the nucleus accumbens core and shell is of particular interest because of their association with the rewarding properties of drugs of abuse. Using background subtracted fast scan cyclic voltammetry, we investigated the effects of dopamine D2 and D3 agonists on electrically stimulated dopamine release and uptake rates in the mouse caudate putamen and nucleus accumbens core and shell. The dopamine D2 agonists (−)-quinpirole hydrochloride and 5,6,7,8-tetrahydro-6-(2-propen-1-yl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (B-HT 920) had the same dopamine release inhibition effects on caudate putamen and nucleus accumbens (core and shell) on the basis of their EC50 values and efficacies. This suggests that the dopamine D2 autoreceptor functionality is comparable in all three striatal regions investigated. The dopamine D3 agonists (4aR,10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride ((+)-PD 128907) and (±)-7-Hydroxy-2-dipropylaminotetralin hydrobromide (7-OH-DPAT) had a significantly greater effect on dopamine release inhibition in the nucleus accumbens shell than in the caudate putamen. This study confirms that, the dopamine D3 autoreceptor functionality is greater in the nucleus accumbens shell followed by the nucleus accumbens core, with the caudate putamen having the least. Neither dopamine D2 nor D3 agonists affected the uptake rates in nucleus accumbens but concentrations greater than 0.1 μM lowered the uptake rate in caudate putamen. To validate our method of evaluating dopamine D2 and D3 autoreceptors, sulpiride (D2 antagonist) and nafadotride (D3 antagonist) were used to reverse the effects of the dopamine agonists to approximately 100% of the preagonist dopamine release concentration. Finally, these results demonstrate a functional voltammetric assay that characterizes dopamine D2-like agonists as either D2- or D3-preferring agonists by taking advantage of the unique receptor density within the striatum. PMID:20567609
Progress in Cochlear Physiology after Békésy

PubMed Central

Guinan, John J.; Salt, Alec; Cheatham, Mary Ann

2012-01-01

In the fifty years since Békésy was awarded the Nobel Prize, cochlear physiology has blossomed. Many topics that are now current are things Békésy could not have imagined. In this review we start by describing progress in understanding the origin of cochlear gross potentials, particularly the cochlear microphonic, an area in which Békésy had extensive experience. We then review progress in areas of cochlear physiology that were mostly unknown to Békésy, including: (1) stereocilia mechano-electrical transduction, force production, and response amplification, (2) outer hair cell (OHC) somatic motility and its molecular basis in prestin, (3) cochlear amplification and related micromechanics, including the evidence that prestin is the main motor for cochlear amplification, (4) the influence of the tectorial membrane, (5) cochlear micromechanics and the mechanical drives to inner hair cell stereocilia, (6) otoacoustic emissions, and (7) olivocochlear efferents and their influence on cochlear physiology. We then return to a subject that Békésy knew well: cochlear fluids and standing currents, as well as our present understanding of energy dependence on the lateral wall of the cochlea. Finally, we touch on cochlear pathologies including noise damage and aging, with an emphasis on where the field might go in the future. PMID:22633944
Genetic Perturbations Suggest a Role of the Resting Potential in Regulating the Expression of the Ion Channels of the KCNA and HCN families in Octopus Cells of the Ventral Cochlear Nucleus

PubMed Central

Cao, Xiao-Jie; Oertel, Donata

2017-01-01

Low-voltage-activated K+ (gKL) and hyperpolarization-activated mixed cation conductances (gh) mediate currents, IKL and Ih, through channels of the Kv1 (KCNA) and HCN families respectively and give auditory neurons the temporal precision required for signaling information about the onset, fine structure, and time of arrival of sounds. Being partially activated at rest, gKL and gh contribute to the resting potential and shape responses to even small subthreshold synaptic currents. Resting gKL and gh also affect the coupling of somatic depolarization with the generation of action potentials. To learn how these important conductances are regulated we have investigated how genetic perturbations affect their expression in octopus cells of the ventral cochlear nucleus (VCN). We report five new findings: First, the magnitude of gh and gKL varied over more than two-fold between wild type strains of mice. Second, average resting potentials are not different in different strains of mice even in the face of large differences in average gKL and gh. Third, IKL has two components, one being α-dendrotoxin (α-DTX)-sensitive and partially inactivating and the other being α-DTX-insensitive, tetraethylammonium (TEA)-sensitive, and non-inactivating. Fourth, the loss of Kv1.1 results in diminution of the α-DTX-sensitive IKL, and compensatory increased expression of an α-DTX-insensitive, tetraethylammonium (TEA)-sensitive IKL. Fifth, Ih and IKL are balanced at the resting potential in all wild type and mutant octopus cells even when resting potentials vary in individual cells over nearly 10 mV, indicating that the resting potential influences the expression of gh and gKL. The independence of resting potentials on gKL and gh shows that gKL and gh do not, over days or weeks, determine the resting potential but rather that the resting potential plays a role in regulating the magnitude of either or both gKL and gh. PMID:28065805
Graded and discontinuous EphA-ephrinB expression patterns in the developing auditory brainstem

PubMed Central

Wallace, Matthew M.; Harris, J. Aaron; Brubaker, Donald Q.; Klotz, Caitlyn A.; Gabriele, Mark L.

2016-01-01

Eph-ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the assembly of central auditory circuits remains poorly understood. The auditory midbrain, or inferior colliculus (IC) is an intriguing structure for exploring guidance of patterned projections as adjacent subdivisions exhibit distinct organizational features. The central nucleus of the IC (CNIC) and deep aspects of its neighboring lateral cortex (LCIC, Layer 3) are tonotopically-organized and receive layered inputs from primarily downstream auditory sources. While less is known about more superficial aspects of the LCIC, its inputs are multimodal, lack a clear tonotopic order, and appear discontinuous, terminating in modular, patch/matrix-like distributions. Here we utilize X-Gal staining approaches in lacZ mutant mice (ephrin-B2, -B3, and EphA4) to reveal EphA-ephrinB expression patterns in the nascent IC during the period of projection shaping that precedes hearing onset. We also report early postnatal protein expression in the cochlear nuclei, the superior olivary complex, the nuclei of the lateral lemniscus, and relevant midline structures. Continuous ephrin-B2 and EphA4 expression gradients exist along frequency axes of the CNIC and LCIC Layer 3. In contrast, more superficial LCIC localization is not graded, but confined to a series of discrete ephrin-B2 and EphA4-positive Layer 2 modules. While heavily expressed in the midline, much of the auditory brainstem is devoid of ephrin-B3, including the CNIC, LCIC Layer 2 modular fields, the dorsal nucleus of the lateral lemniscus (DNLL), as well as much of the superior olivary complex and cochlear nuclei. Ephrin-B3 LCIC expression appears complementary to that of ephrin-B2 and EphA4, with protein most concentrated in presumptive extramodular zones. Described tonotopic gradients and seemingly complementary modular/extramodular patterns suggest Eph-ephrin guidance in establishing juxtaposed continuous and discrete neural maps in the developing IC prior to experience. PMID:26906676

Graded and discontinuous EphA-ephrinB expression patterns in the developing auditory brainstem.

PubMed

Wallace, Matthew M; Harris, J Aaron; Brubaker, Donald Q; Klotz, Caitlyn A; Gabriele, Mark L

2016-05-01

Eph-ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the assembly of central auditory circuits remains poorly understood. The auditory midbrain, or inferior colliculus (IC) is an intriguing structure for exploring guidance of patterned projections as adjacent subdivisions exhibit distinct organizational features. The central nucleus of the IC (CNIC) and deep aspects of its neighboring lateral cortex (LCIC, Layer 3) are tonotopically-organized and receive layered inputs from primarily downstream auditory sources. While less is known about more superficial aspects of the LCIC, its inputs are multimodal, lack a clear tonotopic order, and appear discontinuous, terminating in modular, patch/matrix-like distributions. Here we utilize X-Gal staining approaches in lacZ mutant mice (ephrin-B2, -B3, and EphA4) to reveal EphA-ephrinB expression patterns in the nascent IC during the period of projection shaping that precedes hearing onset. We also report early postnatal protein expression in the cochlear nuclei, the superior olivary complex, the nuclei of the lateral lemniscus, and relevant midline structures. Continuous ephrin-B2 and EphA4 expression gradients exist along frequency axes of the CNIC and LCIC Layer 3. In contrast, more superficial LCIC localization is not graded, but confined to a series of discrete ephrin-B2 and EphA4-positive Layer 2 modules. While heavily expressed in the midline, much of the auditory brainstem is devoid of ephrin-B3, including the CNIC, LCIC Layer 2 modular fields, the dorsal nucleus of the lateral lemniscus (DNLL), as well as much of the superior olivary complex and cochlear nuclei. Ephrin-B3 LCIC expression appears complementary to that of ephrin-B2 and EphA4, with protein most concentrated in presumptive extramodular zones. Described tonotopic gradients and seemingly complementary modular/extramodular patterns suggest Eph-ephrin guidance in establishing juxtaposed continuous and discrete neural maps in the developing IC prior to experience. Copyright © 2016 Elsevier B.V. All rights reserved.
Music Perception of Cochlear Implant Recipients with Implications for Music Instruction: A Review of Literature

PubMed Central

Hsiao, Feilin; Gfeller, Kate

2013-01-01

This review of literature presents a systematic analysis of the capabilities and limitations of cochlear implant recipients regarding music perception. Specifically, it a) analyzes individual components of music (e.g., rhythm, timbre, and pitch) as they interface with the technical characteristics of cochlear implants and the perceptual abilities of cochlear implant recipients; and b) describes accommodations for music instruction that support successful participation of children with cochlear implants. This article consolidates research studies from various disciplines (audiology, hearing science, speech-language pathology, cochlear implants, and music therapy) to provide practical recommendations for educators in fostering the musical growth of children with cochlear implants. PMID:23469365
Author Correction: Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation.

PubMed

Preissl, Sebastian; Fang, Rongxin; Huang, Hui; Zhao, Yuan; Raviram, Ramya; Gorkin, David U; Zhang, Yanxiao; Sos, Brandon C; Afzal, Veena; Dickel, Diane E; Kuan, Samantha; Visel, Axel; Pennacchio, Len A; Zhang, Kun; Ren, Bing

2018-03-01

In the version of this article initially published online, the accession code was given as GSE1000333. The correct code is GSE100033. The error has been corrected in the print, HTML and PDF versions of the article.
Outcomes of cochlear implantation in deaf children of deaf parents: comparative study.

PubMed

Hassanzadeh, S

2012-10-01

This retrospective study compared the cochlear implantation outcomes of first- and second-generation deaf children. The study group consisted of seven deaf, cochlear-implanted children with deaf parents. An equal number of deaf children with normal-hearing parents were selected by matched sampling as a reference group. Participants were matched based on onset and severity of deafness, duration of deafness, age at cochlear implantation, duration of cochlear implantation, gender, and cochlear implant model. We used the Persian Auditory Perception Test for the Hearing Impaired, the Speech Intelligibility Rating scale, and the Sentence Imitation Test, in order to measure participants' speech perception, speech production and language development, respectively. Both groups of children showed auditory and speech development. However, the second-generation deaf children (i.e. deaf children of deaf parents) exceeded the cochlear implantation performance of the deaf children with hearing parents. This study confirms that second-generation deaf children exceed deaf children of hearing parents in terms of cochlear implantation performance. Encouraging deaf children to communicate in sign language from a very early age, before cochlear implantation, appears to improve their ability to learn spoken language after cochlear implantation.
Cochlear implant revision surgeries in children.

PubMed

Amaral, Maria Stella Arantes do; Reis, Ana Cláudia Mirândola B; Massuda, Eduardo T; Hyppolito, Miguel Angelo

2018-02-16

The surgery during which the cochlear implant internal device is implanted is not entirely free of risks and may produce problems that will require revision surgeries. To verify the indications for cochlear implantation revision surgery for the cochlear implant internal device, its effectiveness and its correlation with certain variables related to language and hearing. A retrospective study of patients under 18 years submitted to cochlear implant Surgery from 2004 to 2015 in a public hospital in Brazil. Data collected were: age at the time of implantation, gender, etiology of the hearing loss, audiological and oral language characteristics of each patient before and after Cochlear Implant surgery and any need for surgical revision and the reason for it. Two hundred and sixty-five surgeries were performed in 236 patients. Eight patients received a bilateral cochlear implant and 10 patients required revision surgery. Thirty-two surgeries were necessary for these 10 children (1 bilateral cochlear implant), of which 21 were revision surgeries. In 2 children, cochlear implant removal was necessary, without reimplantation, one with cochlear malformation due to incomplete partition type I and another due to trauma. With respect to the cause for revision surgery, of the 8 children who were successfully reimplanted, four had cochlear calcification following meningitis, one followed trauma, one exhibited a facial nerve malformation, one experienced a failure of the cochlear implant internal device and one revision surgery was necessary because the electrode was twisted. The incidence of the cochlear implant revision surgery was 4.23%. The period following the revision surgeries revealed an improvement in the subject's hearing and language performance, indicating that these surgeries are valid in most cases. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.
Parental expectations and outcomes of pediatric cochlear implantation.

PubMed

Piazza, Elizabeth; Kandathil, Cherian; Carron, Jeffrey D

2009-10-01

Cochlear implants have been used with increasing frequency over the past twenty years, including very young patients. To determine if parents are satisfied with their children's performance after cochlear implantation. Survey mailed to parents of children receiving cochlear implants. 31 questionnaires were returned out of 69 mailed (45 %). The vast majority of responding parents felt that their children benefited substantially from cochlear implant surgery. Cochlear implantation is effective in helping children develop auditory-oral communication skills. Access to auditory/oral communication programs in this state remains an obstacle in postoperative habilitation.
Distribution of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys.

PubMed

Ito, T; Inoue, K; Takada, M

2015-12-03

Macaque monkeys use complex communication calls and are regarded as a model for studying the coding and decoding of complex sound in the auditory system. However, little is known about the distribution of excitatory and inhibitory neurons in the auditory system of macaque monkeys. In this study, we examined the overall distribution of cell bodies that expressed mRNAs for VGLUT1, and VGLUT2 (markers for glutamatergic neurons), GAD67 (a marker for GABAergic neurons), and GLYT2 (a marker for glycinergic neurons) in the auditory system of the Japanese macaque. In addition, we performed immunohistochemistry for VGLUT1, VGLUT2, and GAD67 in order to compare the distribution of proteins and mRNAs. We found that most of the excitatory neurons in the auditory brainstem expressed VGLUT2. In contrast, the expression of VGLUT1 mRNA was restricted to the auditory cortex (AC), periolivary nuclei, and cochlear nuclei (CN). The co-expression of GAD67 and GLYT2 mRNAs was common in the ventral nucleus of the lateral lemniscus (VNLL), CN, and superior olivary complex except for the medial nucleus of the trapezoid body, which expressed GLYT2 alone. In contrast, the dorsal nucleus of the lateral lemniscus, inferior colliculus, thalamus, and AC expressed GAD67 alone. The absence of co-expression of VGLUT1 and VGLUT2 in the medial geniculate, medial superior olive, and VNLL suggests that synaptic responses in the target neurons of these nuclei may be different between rodents and macaque monkeys. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber).

PubMed

Gessele, Nikodemus; Garcia-Pino, Elisabet; Omerbašić, Damir; Park, Thomas J; Koch, Ursula

2016-01-01

Naked mole-rats (Heterocephalus glaber) live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.
Expanded RNA-binding activities of mammalian Argonaute 2

PubMed Central

Tan, Grace S.; Garchow, Barry G.; Liu, Xuhang; Yeung, Jennifer; Morris, John P.; Cuellar, Trinna L.; McManus, Michael T.; Kiriakidou, Marianthi

2009-01-01

Mammalian Argonaute 2 (Ago2) protein associates with microRNAs (miRNAs) or small interfering RNAs (siRNAs) forming RNA-induced silencing complexes (RISCs/miRNPs). In the present work, we characterize the RNA-binding and nucleolytic activity of recombinant mouse Ago2. Our studies show that recombinant mouse Ago2 binds efficiently to miRNAs forming active RISC. Surprisingly, we find that recombinant mouse Ago2 forms active RISC using pre-miRNAs or long unstructured single stranded RNAs as guides. Furthermore, we demonstrate that, in vivo, endogenous human Ago2 binds directly to pre-miRNAs independently of Dicer, and that Ago2:pre-miRNA complexes are found both in the cytoplasm and in the nucleus of human cells. PMID:19808937
Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral.

PubMed

Lichtenhan, J T; Hartsock, J; Dornhoffer, J R; Donovan, K M; Salt, A N

2016-11-01

Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears. Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate. Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time. Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined. Copyright © 2016 Elsevier B.V. All rights reserved.
Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral

PubMed Central

Lichtenhan, JT; Hartsock, J; Dornhoffer, JR; Donovan, KM; Salt, AN

2016-01-01

Background Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears. New method Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate. Results Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time. Conclusions Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined. PMID:27506463
MRI Evidence of Endolymphatic Impermeability to the Gadolinium Molecule in the In Vivo Mouse Inner Ear at 9.4 Tesla

PubMed Central

Counter, S Allen; Nikkhou, Sahar; Brené, Stefan; Damberg, Peter; Sierakowiak, Adam; Klason, Tomas; Berglin, Cecilia Engmér; Laurell, Göran

2013-01-01

Objective: Previous in vivo experimental magnetic resonance imaging (MRI) investigations of the mammalian inner ear at 4.7 Tesla have indicated that intravenously injected gadolinium (Gd) penetrates the perilymphatic labyrinth, but not the endolymphatic membranous labyrinth. In the present study, high field MRI at 9.4T was used to visualize the in vivo mouse vestibulo-cochlea system, and to determine whether the endolymphatic system is permeable to a Gd complex. Methods: A 9.4 T Varian magnet equipped with a 12 cm inner diameter gradient system with maximum gradient strength of 600 mT/m, a millipede coil (Varian design) and a Gd contrast agent were used for image acquisition in the normal C57 BL-6 mouse. Results: High-resolution 2D and 3D images of the mouse cochlea were acquired within 80 minutes following intravenous injection of Gd. Gd initially permeated the perilymphatic scala tympani and scala vestibuli, and permitted visualization of both cochlear turns from base to apex. The superior, inferior and lateral semicircular canals were subsequently visualized in 3 planes. The membranous endolymphatic labyrinth was impermeable to intravenously injected Gd, and thus showed no apparent uptake of Gd at 9.4T. Conclusion: The 9.4T field strength MRI permitted acquisition of high resolution images of anatomical and physiological features of the normal, wild type mouse perilymphatic inner ear in vivo, and provided further evidence that the endolymphatic system is impermeable to intravenously injected Gd. PMID:23894262
Cortical contributions to the auditory frequency-following response revealed by MEG

PubMed Central

Coffey, Emily B. J.; Herholz, Sibylle C.; Chepesiuk, Alexander M. P.; Baillet, Sylvain; Zatorre, Robert J.

2016-01-01

The auditory frequency-following response (FFR) to complex periodic sounds is used to study the subcortical auditory system, and has been proposed as a biomarker for disorders that feature abnormal sound processing. Despite its value in fundamental and clinical research, the neural origins of the FFR are unclear. Using magnetoencephalography, we observe a strong, right-asymmetric contribution to the FFR from the human auditory cortex at the fundamental frequency of the stimulus, in addition to signal from cochlear nucleus, inferior colliculus and medial geniculate. This finding is highly relevant for our understanding of plasticity and pathology in the auditory system, as well as higher-level cognition such as speech and music processing. It suggests that previous interpretations of the FFR may need re-examination using methods that allow for source separation. PMID:27009409
Cochlear implantation in patients with bilateral cochlear trauma.

PubMed

Serin, Gediz Murat; Derinsu, Ufuk; Sari, Murat; Gergin, Ozgül; Ciprut, Ayça; Akdaş, Ferda; Batman, Cağlar

2010-01-01

Temporal bone fracture, which involves the otic capsule, can lead to complete loss of auditory and vestibular functions, whereas the patients without fractures may experience profound sensorineural hearing loss due to cochlear concussion. Cochlear implant is indicated in profound sensorineural hearing loss due to cochlear trauma but who still have an intact auditory nerve. This is a retrospective review study. We report 5 cases of postlingually deafened patients caused by cochlear trauma, who underwent cochlear implantation. Preoperative and postoperative hearing performance will be presented. These patients are cochlear implanted after the cochlear trauma in our department between 2001 and 2006. All patients performed very well with their implants, obtained open-set speech understanding. They all became good telephone users after implantation. Their performance in speech understanding was comparable to standard postlingual adult patients implanted. Cochlear implantation is an effective aural rehabilitation in profound sensorineural hearing loss caused by temporal bone trauma. Preoperative temporal bone computed tomography, magnetic resonance imaging, and promontorium stimulation testing are necessary to make decision for the surgery and to determine the side to be implanted. Surgery could be challenging and complicated because of anatomical irregularity. Moreover, fibrosis and partial or total ossification within the cochlea must be expected. Copyright 2010. Published by Elsevier Inc.
Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy

PubMed Central

Noda, Teppei; Meas, Steven J.; Nogami, Jumpei; Amemiya, Yutaka; Uchi, Ryutaro; Ohkawa, Yasuyuki; Nishimura, Koji; Dabdoub, Alain

2018-01-01

Primary auditory neurons (PANs) play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs), comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs). The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs. PMID:29492404
Vesicular Glutamate Transporters: Spatio-Temporal Plasticity following Hearing Loss

PubMed Central

Fyk-Kolodziej, Bozena; Shimano, Takashi; Gong, Tzy-Wen; Holt, Avril Genene

2011-01-01

An immunocytochemical comparison of vGluT1 and vGluT3 in the cochlear nucleus (CN) of deafened versus normal hearing rats showed the first example of vGluT3 immunostaining in the dorsal and ventral CN and revealed temporal and spatial changes in vGluT1 localization in the CN after cochlear injury. In normal hearing rats vGluT1 immunostaining was restricted to terminals on CN neurons while vGluT3 immunolabeled the somata of the neurons. This changed in the VCN three days following deafness, where vGluT1 immunostaining was no longer seen in large auditory nerve terminals but was instead found in somata of VCN neurons. In the DCN, while vGluT1 labeling of terminals decreased, there was no labeling of neuronal somata. Therefore, loss of peripheral excitatory input results in co-localization of vGluT1 and vGluT3 in VCN neuronal somata. Postsynaptic glutamatergic neurons can use retrograde signaling to control their presynaptic inputs and these results suggest vGluTs could play a role in regulating retrograde signaling in the CN under different conditions of excitatory input. Changes in vGluT gene expression in CN neurons were found three weeks following deafness using qRT-PCR with significant increases in vGluT1 gene expression in both ventral and dorsal CN while vGluT3 gene expression decreased in VCN but increased in DCN. PMID:21211553
The representation of sound localization cues in the barn owl's inferior colliculus

PubMed Central

Singheiser, Martin; Gutfreund, Yoram; Wagner, Hermann

2012-01-01

The barn owl is a well-known model system for studying auditory processing and sound localization. This article reviews the morphological and functional organization, as well as the role of the underlying microcircuits, of the barn owl's inferior colliculus (IC). We focus on the processing of frequency and interaural time (ITD) and level differences (ILD). We first summarize the morphology of the sub-nuclei belonging to the IC and their differentiation by antero- and retrograde labeling and by staining with various antibodies. We then focus on the response properties of neurons in the three major sub-nuclei of IC [core of the central nucleus of the IC (ICCc), lateral shell of the central nucleus of the IC (ICCls), and the external nucleus of the IC (ICX)]. ICCc projects to ICCls, which in turn sends its information to ICX. The responses of neurons in ICCc are sensitive to changes in ITD but not to changes in ILD. The distribution of ITD sensitivity with frequency in ICCc can only partly be explained by optimal coding. We continue with the tuning properties of ICCls neurons, the first station in the midbrain where the ITD and ILD pathways merge after they have split at the level of the cochlear nucleus. The ICCc and ICCls share similar ITD and frequency tuning. By contrast, ICCls shows sigmoidal ILD tuning which is absent in ICCc. Both ICCc and ICCls project to the forebrain, and ICCls also projects to ICX, where space-specific neurons are found. Space-specific neurons exhibit side peak suppression in ITD tuning, bell-shaped ILD tuning, and are broadly tuned to frequency. These neurons respond only to restricted positions of auditory space and form a map of two-dimensional auditory space. Finally, we briefly review major IC features, including multiplication-like computations, correlates of echo suppression, plasticity, and adaptation. PMID:22798945
The effect of instantaneous input dynamic range setting on the speech perception of children with the nucleus 24 implant.

PubMed

Davidson, Lisa S; Skinner, Margaret W; Holstad, Beth A; Fears, Beverly T; Richter, Marie K; Matusofsky, Margaret; Brenner, Christine; Holden, Timothy; Birath, Amy; Kettel, Jerrica L; Scollie, Susan

2009-06-01

The purpose of this study was to examine the effects of a wider instantaneous input dynamic range (IIDR) setting on speech perception and comfort in quiet and noise for children wearing the Nucleus 24 implant system and the Freedom speech processor. In addition, children's ability to understand soft and conversational level speech in relation to aided sound-field thresholds was examined. Thirty children (age, 7 to 17 years) with the Nucleus 24 cochlear implant system and the Freedom speech processor with two different IIDR settings (30 versus 40 dB) were tested on the Consonant Nucleus Consonant (CNC) word test at 50 and 60 dB SPL, the Bamford-Kowal-Bench Speech in Noise Test, and a loudness rating task for four-talker speech noise. Aided thresholds for frequency-modulated tones, narrowband noise, and recorded Ling sounds were obtained with the two IIDRs and examined in relation to CNC scores at 50 dB SPL. Speech Intelligibility Indices were calculated using the long-term average speech spectrum of the CNC words at 50 dB SPL measured at each test site and aided thresholds. Group mean CNC scores at 50 dB SPL with the 40 IIDR were significantly higher (p < 0.001) than with the 30 IIDR. Group mean CNC scores at 60 dB SPL, loudness ratings, and the signal to noise ratios-50 for Bamford-Kowal-Bench Speech in Noise Test were not significantly different for the two IIDRs. Significantly improved aided thresholds at 250 to 6000 Hz as well as higher Speech Intelligibility Indices afforded improved audibility for speech presented at soft levels (50 dB SPL). These results indicate that an increased IIDR provides improved word recognition for soft levels of speech without compromising comfort of higher levels of speech sounds or sentence recognition in noise.
Abnormalities in whisking behaviour are associated with lesions in brain stem nuclei in a mouse model of amyotrophic lateral sclerosis.

PubMed

Grant, Robyn A; Sharp, Paul S; Kennerley, Aneurin J; Berwick, Jason; Grierson, Andrew; Ramesh, Tennore; Prescott, Tony J

2014-02-01

The transgenic SOD1(G93A) mouse is a model of human amyotrophic lateral sclerosis (ALS) and recapitulates many of the pathological hallmarks observed in humans, including motor neuron degeneration in the brain and the spinal cord. In mice, neurodegeneration particularly impacts on the facial nuclei in the brainstem. Motor neurons innervating the whisker pad muscles originate in the facial nucleus of the brain stem, with contractions of these muscles giving rise to "whisking" one of the fastest movements performed by mammals. A longitudinal study was conducted on SOD1(G93A) mice and wild-type litter mate controls, comparing: (i) whisker movements using high-speed video recordings and automated whisker tracking, and (ii) facial nucleus degeneration using MRI. Results indicate that while whisking still occurs in SOD1(G93A) mice and is relatively resistant to neurodegeneration, there are significant disruptions to certain whisking behaviours, which correlate with facial nuclei lesions, and may be as a result of specific facial muscle degeneration. We propose that measures of mouse whisker movement could potentially be used in tandem with measures of limb dysfunction as biomarkers of disease onset and progression in ALS mice and offers a novel method for testing the efficacy of novel therapeutic compounds. Copyright © 2013 Elsevier B.V. All rights reserved.
Orientation-selective Responses in the Mouse Lateral Geniculate Nucleus

PubMed Central

Zhao, Xinyu; Chen, Hui; Liu, Xiaorong

2013-01-01

The dorsal lateral geniculate nucleus (dLGN) receives visual information from the retina and transmits it to the cortex. In this study, we made extracellular recordings in the dLGN of both anesthetized and awake mice, and found that a surprisingly high proportion of cells were selective for stimulus orientation. The orientation selectivity of dLGN cells was unchanged after silencing the visual cortex pharmacologically, indicating that it is not due to cortical feedback. The orientation tuning of some dLGN cells correlated with their elongated receptive fields, while in others orientation selectivity was observed despite the fact that their receptive fields were circular, suggesting that their retinal input might already be orientation selective. Consistently, we revealed orientation/axis-selective ganglion cells in the mouse retina using multielectrode arrays in an in vitro preparation. Furthermore, the orientation tuning of dLGN cells was largely maintained at different stimulus contrasts, which could be sufficiently explained by a simple linear feedforward model. We also compared the degree of orientation selectivity in different visual structures under the same recording condition. Compared with the dLGN, orientation selectivity is greatly improved in the visual cortex, but is similar in the superior colliculus, another major retinal target. Together, our results demonstrate prominent orientation selectivity in the mouse dLGN, which may potentially contribute to visual processing in the cortex. PMID:23904611

Subcellular localization and cytoplasmic complex status of endogenous Keap1.

PubMed

Watai, Yoriko; Kobayashi, Akira; Nagase, Hiroko; Mizukami, Mio; McEvoy, Justina; Singer, Jeffrey D; Itoh, Ken; Yamamoto, Masayuki

2007-10-01

Keap1 acts as a sensor for oxidative/electrophilic stress, an adaptor for Cullin-3-based ubiquitin ligase, and a regulator of Nrf2 activity through the interaction with Nrf2 Neh2 domain. However, the mechanism(s) of Nrf2 migration into the nucleus in response to stress remains largely unknown due to the lack of a reliable antibody for the detection of endogenous Keap1 molecule. Here, we report the generation of a new monoclonal antibody for the detection of endogenous Keap1 molecules. Immunocytochemical analysis of mouse embryonic fibroblasts with the antibody revealed that under normal, unstressed condition, Keap1 is localized primarily in the cytoplasm with minimal amount in the nucleus and endoplasmic reticulum. This subcellular localization profile of Keap1 appears unchanged after treatment of cells with diethyl maleate, an electrophile, and/or Leptomycin B, a nuclear export inhibitor. Subcellular fractionation analysis of mouse liver cells showed similar results. No substantial change in the subcellular distribution profile could be observed in cells isolated from butylated hydroxyanisole-treated mice. Analyses of sucrose density gradient centrifugation of mouse liver cells indicated that Keap1 appears to form multiprotein complexes in the cytoplasm. These results demonstrate that endogenous Keap1 remains mostly in the cytoplasm, and electrophiles promote nuclear accumulation of Nrf2 without altering the subcellular localization of Keap1.
Neuronal calcium sensor-1 deletion in the mouse decreases motivation and dopamine release in the nucleus accumbens.

PubMed

Ng, Enoch; Varaschin, Rafael K; Su, Ping; Browne, Caleb J; Hermainski, Joanna; Le Foll, Bernard; Pongs, Olaf; Liu, Fang; Trudeau, Louis-Eric; Roder, John C; Wong, Albert H C

2016-03-15

Calcium sensors detect intracellular calcium changes and interact with downstream targets to regulate many functions. Neuronal Calcium Sensor-1 (NCS-1) or Frequenin is widely expressed in the nervous system, and involved in neurotransmission, synaptic plasticity and learning. NCS-1 interacts with and regulates dopamine D2 receptor (D2R) internalization and is implicated in disorders like schizophrenia and substance abuse. However, the role of NCS-1 in behaviors dependent on dopamine signaling in the striatum, where D2R is most highly expressed, is unknown. We show that Ncs-1 deletion in the mouse decreases willingness to work for food. Moreover, Ncs-1 knockout mice have significantly lower activity-dependent dopamine release in the nucleus accumbens core in acute slice recordings. In contrast, food preference, responding for conditioned reinforcement, ability to represent changes in reward value, and locomotor response to amphetamine are not impaired. These studies identify novel roles for NCS-1 in regulating activity-dependent striatal dopamine release and aspects of motivated behavior. Copyright © 2015 Elsevier B.V. All rights reserved.
Cochlear implant in Hong Kong Cantonese.

PubMed

Tang, S O; Luk, W S; Lau, C C; So, K W; Wong, C M; Yiu, M L; Kwok, C L

1990-11-01

Cochlear implant surgery was performed in four Cantonese-speaking postlingually deaf Chinese adults, using the House/3M single channel device. This article outlines the methodology, including preoperative assessment and postoperative rehabilitation; and explains the necessary modifications in speech and audiologic work-up in Cantonese-speaking patients. Salient features of Cantonese phonetics, especially its tonal characteristics, are described. The findings of the study are presented. The results of the cochlear implant would suggest a performance superior to that of the hearing aid. Furthermore, the cochlear implant is able to detect tonal cues. This quality of the cochlear implant may prove to be a valuable asset to a tonal language-speaking cochlear implantee.
Visualization and contractile activity of cochlear pericytes in the capillaries of the spiral ligament.

PubMed

Dai, Min; Nuttall, Alfred; Yang, Yue; Shi, Xiaorui

2009-08-01

Pericytes, mural cells located on microvessels, are considered to play an important role in the formation of the vasculature and the regulation of local blood flow in some organs. Little is known about the physiology of cochlear pericytes. In order to investigate the function of cochlear pericytes, we developed a method to visualize cochlear pericytes using diaminofluorescein-2 diacetate (DAF-2DA) and intravital fluorescence microscopy. This method can permit the study of the effect of vasoactive agents on pericytes under the in vivo and normal physiological condition. The specificity of the labeling method was verified by the immunofluorescence labeling of pericyte maker proteins such as desmin, neural proteoglycan (NG2), and thymocyte differentiation antigen 1 (Thy-1). Superfused K(+) and Ca(2+) to the cochlear lateral wall resulted in localized constriction of capillaries at pericyte locations both in vivo and in vitro, while there was no obvious change in cochlear capillary diameters with application of the adrenergic neurotransmitter noradrenaline. The method could be an effective way to visualize cochlear pericytes and microvessels and study lateral wall vascular physiology. Moreover, we demonstrate for the first time that cochlear pericytes have contractility, which may be important for regulation of cochlear blood flow.
Cochlear implants: system design, integration, and evaluation.

PubMed

Zeng, Fan-Gang; Rebscher, Stephen; Harrison, William; Sun, Xiaoan; Feng, Haihong

2008-01-01

As the most successful neural prosthesis, cochlear implants have provided partial hearing to more than 120000 persons worldwide; half of which being pediatric users who are able to develop nearly normal language. Biomedical engineers have played a central role in the design, integration and evaluation of the cochlear implant system, but the overall success is a result of collaborative work with physiologists, psychologists, physicians, educators, and entrepreneurs. This review presents broad yet in-depth academic and industrial perspectives on the underlying research and ongoing development of cochlear implants. The introduction accounts for major events and advances in cochlear implants, including dynamic interplays among engineers, scientists, physicians, and policy makers. The review takes a system approach to address critical issues in cochlear implant research and development. First, the cochlear implant system design and specifications are laid out. Second, the design goals, principles, and methods of the subsystem components are identified from the external speech processor and radio frequency transmission link to the internal receiver, stimulator and electrode arrays. Third, system integration and functional evaluation are presented with respect to safety, reliability, and challenges facing the present and future cochlear implant designers and users. Finally, issues beyond cochlear implants are discussed to address treatment options for the entire spectrum of hearing impairment as well as to use the cochlear implant as a model to design and evaluate other similar neural prostheses such as vestibular and retinal implants.
Cochlear Implants Special Issue Article: Vocal Emotion Recognition by Normal-Hearing Listeners and Cochlear Implant Users

PubMed Central

Luo, Xin; Fu, Qian-Jie; Galvin, John J.

2007-01-01

The present study investigated the ability of normal-hearing listeners and cochlear implant users to recognize vocal emotions. Sentences were produced by 1 male and 1 female talker according to 5 target emotions: angry, anxious, happy, sad, and neutral. Overall amplitude differences between the stimuli were either preserved or normalized. In experiment 1, vocal emotion recognition was measured in normal-hearing and cochlear implant listeners; cochlear implant subjects were tested using their clinically assigned processors. When overall amplitude cues were preserved, normal-hearing listeners achieved near-perfect performance, whereas listeners with cochlear implant recognized less than half of the target emotions. Removing the overall amplitude cues significantly worsened mean normal-hearing and cochlear implant performance. In experiment 2, vocal emotion recognition was measured in listeners with cochlear implant as a function of the number of channels (from 1 to 8) and envelope filter cutoff frequency (50 vs 400 Hz) in experimental speech processors. In experiment 3, vocal emotion recognition was measured in normal-hearing listeners as a function of the number of channels (from 1 to 16) and envelope filter cutoff frequency (50 vs 500 Hz) in acoustic cochlear implant simulations. Results from experiments 2 and 3 showed that both cochlear implant and normal-hearing performance significantly improved as the number of channels or the envelope filter cutoff frequency was increased. The results suggest that spectral, temporal, and overall amplitude cues each contribute to vocal emotion recognition. The poorer cochlear implant performance is most likely attributable to the lack of salient pitch cues and the limited functional spectral resolution. PMID:18003871
The Impact of Entropy on the Spatial Organization of Synaptonemal Complexes within the Cell Nucleus

PubMed Central

Fritsche, Miriam; Reinholdt, Laura G.; Lessard, Mark; Handel, Mary Ann; Bewersdorf, Jörg; Heermann, Dieter W.

2012-01-01

We employ 4Pi-microscopy to study SC organization in mouse spermatocyte nuclei allowing for the three-dimensional reconstruction of the SC's backbone arrangement. Additionally, we model the SCs in the cell nucleus by confined, self-avoiding polymers, whose chain ends are attached to the envelope of the confining cavity and diffuse along it. This work helps to elucidate the role of entropy in shaping pachytene SC organization. The framework provided by the complex interplay between SC polymer rigidity, tethering and confinement is able to qualitatively explain features of SC organization, such as mean squared end-to-end distances, mean squared center-of-mass distances, or SC density distributions. However, it fails in correctly assessing SC entanglement within the nucleus. In fact, our analysis of the 4Pi-microscopy images reveals a higher ordering of SCs within the nuclear volume than what is expected by our numerical model. This suggests that while effects of entropy impact SC organization, the dedicated action of proteins or actin cables is required to fine-tune the spatial ordering of SCs within the cell nucleus. PMID:22574147
Multi-color fluorescence imaging of sub-cellular dynamics of cancer cells in live mice

NASA Astrophysics Data System (ADS)

Hoffman, Robert M.

2006-02-01

We have genetically engineered dual-color fluorescent cells with one color in the nucleus and the other in the cytoplasm that enables real-time nuclear-cytoplasmic dynamics to be visualized in living cells in the cytoplasm in vivo as well as in vitro. To obtain the dual-color cells, red fluorescent protein (RFP) was expressed of the cancer cells, and green fluorescent protein (GFP) linked to histone H2B was expressed in the nucleus. Mitotic cells were visualized by whole-body imaging after injection in the mouse ear. Common carotid artery or heart injection of dual-color cells and a reversible skin flap enabled the external visualization of the dual-color cells in microvessels in the mouse where extreme elongation of the cell body as well as the nucleus occurred. The migration velocities of the dual-color cancer cells in the capillaries were measured by capturing individual images of the dual-color fluorescent cells over time. Human HCT-116-GFP-RFP colon cancer and mouse mammary tumor (MMT)-GFP-RFP cells were injected in the portal vein of nude mice. Extensive clasmocytosis (destruction of the cytoplasm) of the HCT-116-GFP-RFP cells occurred within 6 hours. The data suggest rapid death of HCT-116-GFP-RFP cells in the portal vein. In contrast, MMT-GFP-RFP cells injected into the portal vein mostly survived and formed colonies in the liver. However, when the host mice were pretreated with cyclophosphamide, the HCT-116-GFP-RFP cells also survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the HCT-116-GFP-RFP cells but could not effectively kill the MMT-GFP-RFP cells. With the ability to continuously image cancer cells at the subcellular level in the live animal, our understanding of the complex steps of metastasis will significantly increase. In addition, new drugs can be developed to target these newly visible steps of metastasis.
Processing of speech temporal and spectral information by users of auditory brainstem implants and cochlear implants.

PubMed

Azadpour, Mahan; McKay, Colette M

2014-01-01

Auditory brainstem implants (ABI) use the same processing strategy as was developed for cochlear implants (CI). However, the cochlear nucleus (CN), the stimulation site of ABIs, is anatomically and physiologically more complex than the auditory nerve and consists of neurons with differing roles in auditory processing. The aim of this study was to evaluate the hypotheses that ABI users are less able than CI users to access speech spectro-temporal information delivered by the existing strategies and that the sites stimulated by different locations of CI and ABI electrode arrays differ in encoding of temporal patterns in the stimulation. Six CI users and four ABI users of Nucleus implants with ACE processing strategy participated in this study. Closed-set perception of aCa syllables (16 consonants) and bVd words (11 vowels) was evaluated via experimental processing strategies that activated one, two, or four of the electrodes of the array in a CIS manner as well as subjects' clinical strategies. Three single-channel strategies presented the overall temporal envelope variations of the signal on a single-implant electrode located at the high-, medium-, and low-frequency regions of the array. Implantees' ability to discriminate within electrode temporal patterns of stimulation for phoneme perception and their ability to make use of spectral information presented by increased number of active electrodes were assessed in the single- and multiple-channel strategies, respectively. Overall percentages and information transmission of phonetic features were obtained for each experimental program. Phoneme perception performance of three ABI users was within the range of CI users in most of the experimental strategies and improved as the number of active electrodes increased. One ABI user performed close to chance with all the single and multiple electrode strategies. There was no significant difference between apical, basal, and middle CI electrodes in transmitting speech temporal information, except a trend that the voicing feature was the least transmitted by the basal electrode. A similar electrode-location pattern could be observed in most ABI subjects. Although the number of tested ABI subjects was small, their wide range of phoneme perception performance was consistent with previous reports of overall speech perception in ABI patients. The better-performing ABI user participants had access to speech temporal and spectral information that was comparable to that of average CI user. The poor-performing ABI user did not have access to within-channel speech temporal information and did not benefit from an increased number of spectral channels. The within-subject variability between different ABI electrodes was less than the variability across users in transmission of speech temporal information. The difference in the performance of ABI users could be related to the location of their electrode array on the CN, anatomy, and physiology of their CN or the damage to their auditory brainstem due to tumor or surgery.
Changes in neuropeptide Y receptors and pro-opiomelanocortin in the anorexia (anx/anx) mouse hypothalamus.

PubMed

Broberger, C; Johansen, J; Brismar, H; Johansson, C; Schalling, M; Hökfelt, T

1999-08-15

The pro-opiomelanocortinergic (POMCergic) system originating in the hypothalamic arcuate nucleus extends projections widely over the brain and has been shown to be intricately linked and parallel to the arcuate neuropeptide Y (NPY) system. Both NPY and POMC-derived peptides (melanocortins) have been strongly implicated in the control of feeding behavior, with the former exerting orexigenic effects and the latter having anorexigenic properties. Mice homozygous for the lethal anorexia (anx) mutation are hypophagic, emaciated, and exhibit anomalous processing of NPY exclusively in the arcuate nucleus, providing an interesting model to study NPY-POMC interactions. In the present study, several morphological markers were used to investigate the histochemistry and morphology of the POMC system in anx/anx mice. In situ hybridization demonstrated decreased numbers of POMC mRNA-expressing neurons in the anx/anx arcuate nucleus. In parallel, mRNA levels for both the NPY Y1 and Y5 receptors, which are expressed in POMC neurons, were decreased. Also, expression of the NPY Y2 autoreceptor was attenuated. Immunohistochemistry using antibodies against adrenocorticotropic hormone to demonstrate POMC cell bodies, against alpha-melanocyte-stimulating hormone to demonstrate axonal projections and against the NPY Y1 receptor to demonstrate dendritic arborizations, showed strikingly decreased immunoreactivities for all these markers. The present data suggest that degeneration of the arcuate POMC system is a feature characteristic of the anx/anx mouse. The possible relationship to the NPYergic phenotype of this animal is discussed.
Cellular dosimetry calculations for Strontium-90 using Monte Carlo code PENELOPE.

PubMed

Hocine, Nora; Farlay, Delphine; Boivin, Georges; Franck, Didier; Agarande, Michelle

2014-11-01

To improve risk assessments associated with chronic exposure to Strontium-90 (Sr-90), for both the environment and human health, it is necessary to know the energy distribution in specific cells or tissue. Monte Carlo (MC) simulation codes are extremely useful tools for calculating deposition energy. The present work was focused on the validation of the MC code PENetration and Energy LOss of Positrons and Electrons (PENELOPE) and the assessment of dose distribution to bone marrow cells from punctual Sr-90 source localized within the cortical bone part. S-values (absorbed dose per unit cumulated activity) calculations using Monte Carlo simulations were performed by using PENELOPE and Monte Carlo N-Particle eXtended (MCNPX). Cytoplasm, nucleus, cell surface, mouse femur bone and Sr-90 radiation source were simulated. Cells are assumed to be spherical with the radii of the cell and cell nucleus ranging from 2-10 μm. The Sr-90 source is assumed to be uniformly distributed in cell nucleus, cytoplasm and cell surface. The comparison of S-values calculated with PENELOPE to MCNPX results and the Medical Internal Radiation Dose (MIRD) values agreed very well since the relative deviations were less than 4.5%. The dose distribution to mouse bone marrow cells showed that the cells localized near the cortical part received the maximum dose. The MC code PENELOPE may prove useful for cellular dosimetry involving radiation transport through materials other than water, or for complex distributions of radionuclides and geometries.
Visualization of spiral ganglion neurites within the scala tympani with a cochlear implant in situ

PubMed Central

Chikar, Jennifer A.; Batts, Shelley A.; Pfingst, Bryan E.; Raphael, Yehoash

2009-01-01

Current cochlear histology methods do not allow in situ processing of cochlear implants. The metal components of the implant preclude standard embedding and mid-modiolar sectioning, and whole mounts do not have the spatial resolution needed to view the implant within the scala tympani. One focus of recent auditory research is the regeneration of structures within the cochlea, particularly the ganglion cells and their processes, and there are multiple potential benefits to cochlear implant users from this work. To facilitate experimental investigations of auditory nerve regeneration performed in conjunction with cochlear implantation, it is critical to visualize the cochlear tissue and the implant together to determine if the nerve has made contact with the implant. This paper presents a novel histological technique that enables simultaneous visualization of the in situ cochlear implant and neurofilament – labeled nerve processes within the scala tympani, and the spatial relationship between them. PMID:19428528
Visualization of spiral ganglion neurites within the scala tympani with a cochlear implant in situ.

PubMed

Chikar, Jennifer A; Batts, Shelley A; Pfingst, Bryan E; Raphael, Yehoash

2009-05-15

Current cochlear histology methods do not allow in situ processing of cochlear implants. The metal components of the implant preclude standard embedding and mid-modiolar sectioning, and whole mounts do not have the spatial resolution needed to view the implant within the scala tympani. One focus of recent auditory research is the regeneration of structures within the cochlea, particularly the ganglion cells and their processes, and there are multiple potential benefits to cochlear implant users from this work. To facilitate experimental investigations of auditory nerve regeneration performed in conjunction with cochlear implantation, it is critical to visualize the cochlear tissue and the implant together to determine if the nerve has made contact with the implant. This paper presents a novel histological technique that enables simultaneous visualization of the in situ cochlear implant and neurofilament-labeled nerve processes within the scala tympani, and the spatial relationship between them.
[Emotional response to music by postlingually-deafened adult cochlear implant users].

PubMed

Wang, Shuo; Dong, Ruijuan; Zhou, Yun; Li, Jing; Qi, Beier; Liu, Bo

2012-10-01

To assess the emotional response to music by postlingually-deafened adult cochlear implant users. Munich music questionnaire (MUMU) was used to match the music experience and the motivation of use of music between 12 normal-hearing and 12 cochlear implant subjects. Emotion rating test in Musical Sounds in Cochlear Implants (MuSIC) test battery was used to assess the emotion perception ability for both normal-hearing and cochlear implant subjects. A total of 15 pieces of music phases were used. Responses were given by selecting the rating scales from 1 to 10. "1" represents "very sad" feeling, and "10" represents "very happy feeling. In comparison with normal-hearing subjects, 12 cochlear implant subjects made less active use of music for emotional purpose. The emotion ratings for cochlear implant subjects were similar to normal-hearing subjects, but with large variability. Post-lingually deafened cochlear implant subjects on average performed similarly in emotion rating tasks relative to normal-hearing subjects, but their active use of music for emotional purpose was obviously less than normal-hearing subjects.
The cochlear size of bats and rodents derived from MRI images and histology.

PubMed

Hsiao, Chun Jen; Jen, Philip Hung-Sun; Wu, Chung Hsin

2015-05-27

From the evolutionary perspective, the ear of each animal species is built for effective processing of the biologically relevant signals used for communication and acoustically guided orientation. Because the sound pulses used by echolocating bats for orientation and rodents for communication are quite different, the basic design of the mammalian auditory system commonly shared by echolocating bats must be specialized in some manner to effectively process their species-specific sounds. The present study examines the difference in the cochlea of these animal species using MRI images and histological techniques. We report here that, although all these animal species share a similar cochlear structure, they vary in their cochlear size and turns. Bats using constant frequency-frequency-modulated pulses (CF-FM bats) and frequency-modulated pulses (FM bats) for echolocation have a larger cochlear size and more cochlear turns than rodents (mice and rats). However, CF-FM bats have the largest cochlear size and most cochlear turns. This difference in cochlear size and turns of these animal species is discussed in relation to their biologically relevant sounds and acoustic behavior.
Guideline on cochlear implants.

PubMed

Manrique, Manuel; Ramos, Ángel; de Paula Vernetta, Carlos; Gil-Carcedo, Elisa; Lassaleta, Luis; Sanchez-Cuadrado, Isabel; Espinosa, Juan Manuel; Batuecas, Ángel; Cenjor, Carlos; Lavilla, María José; Núñez, Faustino; Cavalle, Laura; Huarte, Alicia

2018-03-26

In the last decade numerous hospitals have started to work with patients who are candidates for a cochlear implant (CI) and there have been numerous and relevant advances in the treatment of sensorineural hearing loss that extended the indications for cochlear implants. To provide a guideline on cochlear implants to specialists in otorhinolaryngology, other medical specialities, health authorities and society in general. The Scientific Committees of Otology, Otoneurology and Audiology from the Spanish Society of Otolaryngology and Head and Neck Surgery (SEORL-CCC), in a coordinated and agreed way, performed a review of the current state of CI based on the existing regulations and in the scientific publications referenced in the bibliography of the document drafted. The clinical guideline on cochlear implants provides information on: a) Definition and description of Cochlear Implant; b) Indications for cochlear implants; c) Organizational requirements for a cochlear implant programme. A clinical guideline on cochlear implants has been developed by a Committee of Experts of the SEORL-CCC, to help and guide all the health professionals involved in this field of CI in decision-making to treathearing impairment. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.
Isolating LacZ-expressing cells from mouse inner ear tissues using flow cytometry.

PubMed

Jan, Taha A; Chai, Renjie; Sayyid, Zahra N; Cheng, Alan G

2011-12-23

Isolation of specific cell types allows one to analyze rare cell populations such as stem/progenitor cells. Such an approach to studying inner ear tissues presents a unique challenge because of the paucity of cells of interest and few transgenic reporter mouse models. Here, we describe a protocol using fluorescence-conjugated probes to selectively label LacZ-positive cells from the neonatal cochleae. The most common underlying pathology of sensorineural hearing loss is the irreversible damage and loss of cochlear sensory hair cells, which are required to transduce sound waves to neural impulses. Recent evidence suggests that the murine auditory and vestibular organs harbor stem/progenitor cells that may have regenerative potential. These findings warrant further investigation, including identifying specific cell types with stem/progenitor cell characteristics. The Wnt signaling pathway has been demonstrated to play a critical role in maintaining stem/progenitor cell populations in several organ systems. We have recently identified Wnt-responsive Axin2-expressing cells in the neonatal cochlea, but their function is largely unknown. To better understand the behavior of these Wnt-responsive cells in vitro, we have developed a method of isolating Axin2-expressing cells from cochleae of Axin2-LacZ reporter mice. Using flow cytometry to isolate Axin2-LacZ positive cells from the neonatal cochleae, we could in turn execute a variety of experiments on live cells to interrogate their behavior as stem/progenitor cells. Here, we describe in detail the steps for the microdissection of neonatal cochlea, dissociation of these tissues, labeling of the LacZ-positive cells using a fluorogenic substrate, and cell sorting. Techniques for dissociating cochleae into single cells and isolating cochlear cells via flow cytometry have been described. We have made modifications to these techniques to establish a novel protocol to isolate LacZ-expressing cells from the neonatal cochlea.
Solvent effects on differentiation of mouse brain tissue using laser microdissection ‘cut and drop’ sampling with direct mass spectral analysis

DOE PAGES

Cahill, John F.; Kertesz, Vilmos; Porta, Tiffany; ...

2018-02-08

Rationale: Laser microdissection-liquid vortex capture/electrospray ionization mass spectrometry (LMD-LVC/ESI-MS) has potential for on-line classification of tissue but an investigation into what analytical conditions provide best spectral differentiation has not been conducted. The effects of solvent, ionization polarity, and spectral acquisition parameters on differentiation of mouse brain tissue regions are described.Methods: Individual 40 × 40 μm microdissections from cortex, white, grey, granular, and nucleus regions of mouse brain tissue were analyzed using different capture/ESI solvents, in positive and negative ion mode ESI, using time-of-flight (TOF)-MS and sequential window acquisitions of all theoretical spectra (SWATH)-MS (a permutation of tandem-MS), and combinations thereof.more » Principal component analysis-linear discriminant analysis (PCA-LDA), applied to each mass spectral dataset, was used to determine the accuracy of differentiation of mouse brain tissue regions. Results: Mass spectral differences associated with capture/ESI solvent composition manifested as altered relative distributions of ions rather than the presence or absence of unique ions. In negative ion mode ESI, 80/20 (v/v) methanol/water yielded spectra with low signal/noise ratios relative to other solvents. PCA-LDA models acquired using 90/10 (v/v) methanol/chloroform differentiated tissue regions with 100% accuracy while data collected using methanol misclassified some samples. The combination of SWATH-MS and TOF-MS data improved differentiation accuracy.Conclusions: Combined TOF-MS and SWATH-MS data differentiated white, grey, granular, and nucleus mouse tissue regions with greater accuracy than when solely using TOF-MS data. Using 90/10 (v/v) methanol/chloroform, tissue regions were perfectly differentiated. Lastly, these results will guide future studies looking to utilize the potential of LMD-LVC/ESI-MS for tissue and disease differentiation.« less
Solvent effects on differentiation of mouse brain tissue using laser microdissection ‘cut and drop’ sampling with direct mass spectral analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cahill, John F.; Kertesz, Vilmos; Porta, Tiffany

Rationale: Laser microdissection-liquid vortex capture/electrospray ionization mass spectrometry (LMD-LVC/ESI-MS) has potential for on-line classification of tissue but an investigation into what analytical conditions provide best spectral differentiation has not been conducted. The effects of solvent, ionization polarity, and spectral acquisition parameters on differentiation of mouse brain tissue regions are described.Methods: Individual 40 × 40 μm microdissections from cortex, white, grey, granular, and nucleus regions of mouse brain tissue were analyzed using different capture/ESI solvents, in positive and negative ion mode ESI, using time-of-flight (TOF)-MS and sequential window acquisitions of all theoretical spectra (SWATH)-MS (a permutation of tandem-MS), and combinations thereof.more » Principal component analysis-linear discriminant analysis (PCA-LDA), applied to each mass spectral dataset, was used to determine the accuracy of differentiation of mouse brain tissue regions. Results: Mass spectral differences associated with capture/ESI solvent composition manifested as altered relative distributions of ions rather than the presence or absence of unique ions. In negative ion mode ESI, 80/20 (v/v) methanol/water yielded spectra with low signal/noise ratios relative to other solvents. PCA-LDA models acquired using 90/10 (v/v) methanol/chloroform differentiated tissue regions with 100% accuracy while data collected using methanol misclassified some samples. The combination of SWATH-MS and TOF-MS data improved differentiation accuracy.Conclusions: Combined TOF-MS and SWATH-MS data differentiated white, grey, granular, and nucleus mouse tissue regions with greater accuracy than when solely using TOF-MS data. Using 90/10 (v/v) methanol/chloroform, tissue regions were perfectly differentiated. Lastly, these results will guide future studies looking to utilize the potential of LMD-LVC/ESI-MS for tissue and disease differentiation.« less
Cochlear implants in children implanted in Jordan: A parental overview.

PubMed

Alkhamra, Rana A

2015-07-01

Exploring the perspective of parents on the cochlear implant process in Jordan. Sixty parents of deaf children were surveyed on the information gathering process prior to cochlear implant surgery, and their implant outcome expectations post-surgery. Whether child or parent characteristics may impact parents' post-surgical expectations was explored. Although parents used a variety of information sources when considering a cochlear implant, the ear, nose and throat doctor comprised their major source of information (60%). Parents received a range of information prior to cochlear implant but agreed (93.3%) on the need for a multidisciplinary team approach. Post-surgically, parents' expected major developments in the areas of spoken language (97%), and auditory skills (100%). Receiving education in mainstream schools (92%) was expected too. Parents perceived the cochlear implant decision as the best decision they can make for their child (98.3%). A significant correlation was found between parents contentment with the cochlear implant decision and expecting developments in the area of reading and writing (r=0.7). Child's age at implantation and age at hearing loss diagnosis significantly affected parents' post-implant outcome expectations (p<0.05). Despite the general satisfaction from the information quantity and quality prior to cochlear implant, parents agree on the need for a comprehensive multidisciplinary team approach during the different stages of the cochlear implant process. Parents' education about cochlear implants prior to the surgery can affect their post-surgical outcome expectations. The parental perspective presented in this study can help professionals develop better understanding of parents' needs and expectations and henceforth improve their services and support during the different stages of the cochlear implant process. Copyright © 2015. Published by Elsevier Ireland Ltd.

In vivo imaging of mammalian cochlear blood flow using fluorescence microendoscopy.

PubMed

Monfared, Ashkan; Blevins, Nikolas H; Cheung, Eunice L M; Jung, Juergen C; Popelka, Gerald; Schnitzer, Mark J

2006-02-01

We sought to develop techniques for visualizing cochlear blood flow in live mammalian subjects using fluorescence microendoscopy. Inner ear microcirculation appears to be intimately involved in cochlear function. Blood velocity measurements suggest that intense sounds can alter cochlear blood flow. Disruption of cochlear blood flow may be a significant cause of hearing impairment, including sudden sensorineural hearing loss. However, inability to image cochlear blood flow in a nondestructive manner has limited investigation of the role of inner ear microcirculation in hearing function. Present techniques for imaging cochlear microcirculation using intravital light microscopy involve extensive perturbations to cochlear structure, precluding application in human patients. The few previous endoscopy studies of the cochlea have suffered from optical resolution insufficient for visualizing cochlear microvasculature. Fluorescence microendoscopy is an emerging minimally invasive imaging modality that provides micron-scale resolution in tissues inaccessible to light microscopy. In this article, we describe the use of fluorescence microendoscopy in live guinea pigs to image capillary blood flow and movements of individual red blood cells within the basal turn of the cochlea. We anesthetized eight adult guinea pigs and accessed the inner ear through the mastoid bulla. After intravenous injection of fluorescein dye, we made a limited cochleostomy and introduced a compound doublet gradient refractive index endoscope probe 1 mm in diameter into the inner ear. We then imaged cochlear blood flow within individual vessels in an epifluorescence configuration using one-photon fluorescence microendoscopy. We observed single red blood cells passing through individual capillaries in several cochlear structures, including the round window membrane, spiral ligament, osseous spiral lamina, and basilar membrane. Blood flow velocities within inner ear capillaries varied widely, with observed speeds reaching up to approximately 500 microm/s. Fluorescence microendoscopy permits visualization of cochlear microcirculation with micron-scale optical resolution and determination of blood flow velocities through analysis of video sequences.
Sertad1 encodes a novel transcriptional co-activator of SMAD1 in mouse embryonic hearts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, Yin; Zhao, Shaomin; School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069

2013-11-29

Highlights: •SERTAD1 interacts with SMAD1. •Sertad1 is expressed in mouse embryonic hearts. •SERTAD1 is localized in both cytoplasm and nucleus of cardiomyocytes. •SERTAD1 enhances expression of BMP target cardiogenic genes as a SMAD1 co-activator. -- Abstract: Despite considerable advances in surgical repairing procedures, congenital heart diseases (CHDs) remain the leading noninfectious cause of infant morbidity and mortality. Understanding the molecular/genetic mechanisms underlying normal cardiogenesis will provide essential information for the development of novel diagnostic and therapeutic strategies against CHDs. BMP signaling plays complex roles in multiple cardiogenic processes in mammals. SMAD1 is a canonical nuclear mediator of BMP signaling, themore » activity of which is critically regulated through its interaction partners. We screened a mouse embryonic heart yeast two-hybrid library using Smad1 as bait and identified SERTAD1 as a novel interaction partner of SMAD1. SERTAD1 contains multiple potential functional domains, including two partially overlapping transactivation domains at the C terminus. The SERTAD1-SMAD1 interaction in vitro and in mammalian cells was further confirmed through biochemical assays. The expression of Sertad1 in developing hearts was demonstrated using RT-PCR, western blotting and in situ hybridization analyses. We also showed that SERTAD1 was localized in both the cytoplasm and nucleus of immortalized cardiomyocytes and primary embryonic cardiomyocyte cultures. The overexpression of SERTAD1 in cardiomyocytes not only enhanced the activity of two BMP reporters in a dose-dependent manner but also increased the expression of several known BMP/SMAD regulatory targets. Therefore, these data suggest that SERTAD1 acts as a SMAD1 transcriptional co-activator to promote the expression of BMP target genes during mouse cardiogenesis.« less
A Cre Mouse Line for Probing Irradiance- and Direction-Encoding Retinal Networks

PubMed Central

Sabbah, Shai

2017-01-01

Abstract Cell type-specific Cre driver lines have revolutionized the analysis of retinal cell types and circuits. We show that the transgenic mouse Rbp4-Cre selectively labels several retinal neuronal types relevant to the encoding of absolute light intensity (irradiance) and visual motion. In the ganglion cell layer (GCL), most marked cells are wide-field spiking polyaxonal amacrine cells (ACs) with sustained irradiance-encoding ON responses that persist during chemical synaptic blockade. Their arbors spread about 1 mm across the retina and are restricted to the inner half of the ON sublamina of the inner plexiform layer (IPL). There, they costratify with dendrites of M2 intrinsically photosensitive retinal ganglion cells (ipRGCs), to which they are tracer coupled. We propose that synaptically driven and intrinsic photocurrents of M2 cells pass through gap junctions to drive AC light responses. Also marked in this mouse are two types of RGCs. R-cells have a bistratified dendritic arbor, weak directional tuning, and irradiance-encoding ON responses. However, they also receive excitatory OFF input, revealed during ON-channel blockade. Serial blockface electron microscopic (SBEM) reconstruction confirms OFF bipolar input, and reveals that some OFF input derives from a novel type of OFF bipolar cell (BC). R-cells innervate specific layers of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). The other marked RGC type (RDS) is bistratified, transient, and ON-OFF direction selective (DS). It apparently innervates the nucleus of the optic tract (NOT). The Rbp4-Cre mouse will be valuable for targeting these cell types for further study and for selectively manipulating them for circuit analysis. PMID:28466070
Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments

PubMed Central

Meng, Fanchi; Na, Insung; Kurgan, Lukasz; Uversky, Vladimir N.

2015-01-01

The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions. PMID:26712748
Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area

PubMed Central

Cui, Huxing; Sohn, Jong-Woo; Gautron, Laurent; Funahashi, Hisayuki; Williams, Kevin W.; Elmquist, Joel K.; Lutter, Michael

2013-01-01

The central melanocortin system regulates body energy homeostasis including the melanocortin-4 receptor (MC4R). The lateral hypothalamic area (LHA) receives dense melanocortinergic inputs from the arcuate nucleus of hypothalamus and regulates multiple processes including food intake, reward behaviors and autonomic function. Using a mouse line in which green fluorescent protein (GFP) is expressed under control of MC4R gene promoter, we systemically investigated MC4R signaling in the LHA by combining double immunohistochemistry, electrophysiology and retrograde tracing techniques. We found that LHA MC4R-GFP neurons co-express neurotensin as well as the leptin receptor but not with other peptide neurotransmitters found in the LHA including orexin, melanin concentrating hormone and nesfatin-1. Furthermore, electrophysiological recording demonstrated that leptin, but not the MC4R agonist melanotan II, hyperpolarizes the majority of LHA MC4R-GFP neurons in an ATP-sensitive potassium channel-dependent manner. Retrograde tracing revealed that LHA MC4R-GFP neurons do not project to the ventral tegmental area, dorsal raphe nucleus, nucleus accumbens and spinal cord, and only limited number of neurons project to the nucleus of solitary tract and parabrachial nucleus. Our findings provide new insight into MC4R signaling in the LHA and its potential implication in homeostatic regulation of body energy balance. PMID:22605619
Bilateral cochlear implantation in a patient with bilateral temporal bone fractures.

PubMed

Chung, Jae Ho; Shin, Myung Chul; Min, Hyun Jung; Park, Chul Won; Lee, Seung Hwan

2011-01-01

With the emphasis on bilateral hearing nowadays, bilateral cochlear implantation has been tried out for bilateral aural rehabilitation. Bilateral sensorineural hearing loss caused by head trauma can get help from cochlear implantation. We present the case of a 44-year-old man with bilateral otic capsule violating temporal bone fractures due to head trauma. The patient demonstrated much improved audiometric and psychoacoustic performance after bilateral cochlear implantation. We believe bilateral cochlear implantation in such patient can be a very effective tool for rehabilitation. Copyright © 2011 Elsevier Inc. All rights reserved.
The basic circuit of the IC: tectothalamic neurons with different patterns of synaptic organization send different messages to the thalamus

PubMed Central

Ito, Tetsufumi; Oliver, Douglas L.

2012-01-01

The inferior colliculus (IC) in the midbrain of the auditory system uses a unique basic circuit to organize the inputs from virtually all of the lower auditory brainstem and transmit this information to the medial geniculate body (MGB) in the thalamus. Here, we review the basic circuit of the IC, the neuronal types, the organization of their inputs and outputs. We specifically discuss the large GABAergic (LG) neurons and how they differ from the small GABAergic (SG) and the more numerous glutamatergic neurons. The somata and dendrites of LG neurons are identified by axosomatic glutamatergic synapses that are lacking in the other cell types and exclusively contain the glutamate transporter VGLUT2. Although LG neurons are most numerous in the central nucleus of the IC (ICC), an analysis of their distribution suggests that they are not specifically associated with one set of ascending inputs. The inputs to ICC may be organized into functional zones with different subsets of brainstem inputs, but each zone may contain the same three neuron types. However, the sources of VGLUT2 axosomatic terminals on the LG neuron are not known. Neurons in the dorsal cochlear nucleus, superior olivary complex, intermediate nucleus of the lateral lemniscus, and IC itself that express the gene for VGLUT2 only are the likely origin of the dense VGLUT2 axosomatic terminals on LG tectothalamic neurons. The IC is unique since LG neurons are GABAergic tectothalamic neurons in addition to the numerous glutamatergic tectothalamic neurons. SG neurons evidently target other auditory structures. The basic circuit of the IC and the LG neurons in particular, has implications for the transmission of information about sound through the midbrain to the MGB. PMID:22855671
Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G.

PubMed

Emptoz, Alice; Michel, Vincent; Lelli, Andrea; Akil, Omar; Boutet de Monvel, Jacques; Lahlou, Ghizlene; Meyer, Anaïs; Dupont, Typhaine; Nouaille, Sylvie; Ey, Elody; Franca de Barros, Filipa; Beraneck, Mathieu; Dulon, Didier; Hardelin, Jean-Pierre; Lustig, Lawrence; Avan, Paul; Petit, Christine; Safieddine, Saaid

2017-09-05

Our understanding of the mechanisms underlying inherited forms of inner ear deficits has considerably improved during the past 20 y, but we are still far from curative treatments. We investigated gene replacement as a strategy for restoring inner ear functions in a mouse model of Usher syndrome type 1G, characterized by congenital profound deafness and balance disorders. These mice lack the scaffold protein sans, which is involved both in the morphogenesis of the stereociliary bundle, the sensory antenna of inner ear hair cells, and in the mechanoelectrical transduction process. We show that a single delivery of the sans cDNA by the adenoassociated virus 8 to the inner ear of newborn mutant mice reestablishes the expression and targeting of the protein to the tips of stereocilia. The therapeutic gene restores the architecture and mechanosensitivity of stereociliary bundles, improves hearing thresholds, and durably rescues these mice from the balance defects. Our results open up new perspectives for efficient gene therapy of cochlear and vestibular disorders by showing that even severe dysmorphogenesis of stereociliary bundles can be corrected.
Gene Expression by Mouse Inner Ear Hair Cells during Development

PubMed Central

Scheffer, Déborah I.; Shen, Jun

2015-01-01

Hair cells of the inner ear are essential for hearing and balance. As a consequence, pathogenic variants in genes specifically expressed in hair cells often cause hereditary deafness. Hair cells are few in number and not easily isolated from the adjacent supporting cells, so the biochemistry and molecular biology of hair cells can be difficult to study. To study gene expression in hair cells, we developed a protocol for hair cell isolation by FACS. With nearly pure hair cells and surrounding cells, from cochlea and utricle and from E16 to P7, we performed a comprehensive cell type-specific RNA-Seq study of gene expression during mouse inner ear development. Expression profiling revealed new hair cell genes with distinct expression patterns: some are specific for vestibular hair cells, others for cochlear hair cells, and some are expressed just before or after maturation of mechanosensitivity. We found that many of the known hereditary deafness genes are much more highly expressed in hair cells than surrounding cells, suggesting that genes preferentially expressed in hair cells are good candidates for unknown deafness genes. PMID:25904789
Listening to Another Sense: Somatosensory Integration in the Auditory System

PubMed Central

Wu, Calvin; Stefanescu, Roxana A.; Martel, David T.

2014-01-01

Conventionally, sensory systems are viewed as separate entities, each with its own physiological process serving a different purpose. However, many functions require integrative inputs from multiple sensory systems, and sensory intersection and convergence occur throughout the central nervous system. The neural processes for hearing perception undergo significant modulation by the two other major sensory systems, vision and somatosensation. This synthesis occurs at every level of the ascending auditory pathway: the cochlear nucleus, inferior colliculus, medial geniculate body, and the auditory cortex. In this review, we explore the process of multisensory integration from 1) anatomical (inputs and connections), 2) physiological (cellular responses), 3) functional, and 4) pathological aspects. We focus on the convergence between auditory and somatosensory inputs in each ascending auditory station. This review highlights the intricacy of sensory processing, and offers a multisensory perspective regarding the understanding of sensory disorders. PMID:25526698
Expression pattern in retinal photoreceptors of POMGnT1, a protein involved in muscle-eye-brain disease

PubMed Central

Uribe, Mary Luz; Haro, Carmen; Campello, Laura; Cruces, Jesús; Martín-Nieto, José

2016-01-01

Purpose The POMGNT1 gene, encoding protein O-linked-mannose β-1,2-N-acetylglucosaminyltransferase 1, is associated with muscle-eye-brain disease (MEB) and other dystroglycanopathies. This gene’s lack of function or expression causes hypoglycosylation of α-dystroglycan (α-DG) in the muscle and the central nervous system, including the brain and the retina. The ocular symptoms of patients with MEB include retinal degeneration and detachment, glaucoma, and abnormal electroretinogram. Nevertheless, the POMGnT1 expression pattern in the healthy mammalian retina has not yet been investigated. In this work, we address the expression of the POMGNT1 gene in the healthy retina of a variety of mammals and characterize the distribution pattern of this gene in the adult mouse retina and the 661W photoreceptor cell line. Methods Using reverse transcription (RT)–PCR and immunoblotting, we studied POMGNT1 expression at the mRNA and protein levels in various mammalian species, from rodents to humans. Immunofluorescence confocal microscopy analyses were performed to characterize the distribution profile of its protein product in mouse retinal sections and in 661W cultured cells. The intranuclear distribution of POMT1 and POMT2, the two enzymes preceding POMGnT1 in the α-DG O-mannosyl glycosylation pathway, was also analyzed. Results POMGNT1 mRNA and its encoded protein were expressed in the neural retina of all mammals studied. POMGnT1 was located in the cytoplasmic fraction in the mouse retina and concentrated in the myoid portion of the photoreceptor inner segments, where the protein colocalized with GM130, a Golgi complex marker. The presence of POMGnT1 in the Golgi complex was also evident in 661W cells. However, and in contrast to retinal tissue, POMGnT1 additionally accumulated in the nucleus of the 661W photoreceptors. Colocalization was found within this organelle between POMGnT1 and POMT1/2, the latter associated with euchromatic regions of the nucleus. Conclusions Our results indicate that POMGnT1 participates not only in the synthesis of O-mannosyl glycans added to α-DG in the Golgi complex but also in the glycosylation of other yet-to-be-identified proteins in the nucleus of mouse photoreceptors. PMID:27375352
Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear.

PubMed

Pinyon, Jeremy L; Tadros, Sherif F; Froud, Kristina E; Y Wong, Ann C; Tompson, Isabella T; Crawford, Edward N; Ko, Myungseo; Morris, Renée; Klugmann, Matthias; Housley, Gary D

2014-04-23

The cochlear implant is the most successful bionic prosthesis and has transformed the lives of people with profound hearing loss. However, the performance of the "bionic ear" is still largely constrained by the neural interface itself. Current spread inherent to broad monopolar stimulation of the spiral ganglion neuron somata obviates the intrinsic tonotopic mapping of the cochlear nerve. We show in the guinea pig that neurotrophin gene therapy integrated into the cochlear implant improves its performance by stimulating spiral ganglion neurite regeneration. We used the cochlear implant electrode array for novel "close-field" electroporation to transduce mesenchymal cells lining the cochlear perilymphatic canals with a naked complementary DNA gene construct driving expression of brain-derived neurotrophic factor (BDNF) and a green fluorescent protein (GFP) reporter. The focusing of electric fields by particular cochlear implant electrode configurations led to surprisingly efficient gene delivery to adjacent mesenchymal cells. The resulting BDNF expression stimulated regeneration of spiral ganglion neurites, which had atrophied 2 weeks after ototoxic treatment, in a bilateral sensorineural deafness model. In this model, delivery of a control GFP-only vector failed to restore neuron structure, with atrophied neurons indistinguishable from unimplanted cochleae. With BDNF therapy, the regenerated spiral ganglion neurites extended close to the cochlear implant electrodes, with localized ectopic branching. This neural remodeling enabled bipolar stimulation via the cochlear implant array, with low stimulus thresholds and expanded dynamic range of the cochlear nerve, determined via electrically evoked auditory brainstem responses. This development may broadly improve neural interfaces and extend molecular medicine applications.
Predicting social functioning in children with a cochlear implant and in normal-hearing children: the role of emotion regulation.

PubMed

Wiefferink, Carin H; Rieffe, Carolien; Ketelaar, Lizet; Frijns, Johan H M

2012-06-01

The purpose of the present study was to compare children with a cochlear implant and normal hearing children on aspects of emotion regulation (emotion expression and coping strategies) and social functioning (social competence and externalizing behaviors) and the relation between emotion regulation and social functioning. Participants were 69 children with cochlear implants (CI children) and 67 normal hearing children (NH children) aged 1.5-5 years. Parents answered questionnaires about their children's language skills, social functioning, and emotion regulation. Children also completed simple tasks to measure their emotion regulation abilities. Cochlear implant children had fewer adequate emotion regulation strategies and were less socially competent than normal hearing children. The parents of cochlear implant children did not report fewer externalizing behaviors than those of normal hearing children. While social competence in normal hearing children was strongly related to emotion regulation, cochlear implant children regulated their emotions in ways that were unrelated with social competence. On the other hand, emotion regulation explained externalizing behaviors better in cochlear implant children than in normal hearing children. While better language skills were related to higher social competence in both groups, they were related to fewer externalizing behaviors only in cochlear implant children. Our results indicate that cochlear implant children have less adequate emotion-regulation strategies and less social competence than normal hearing children. Since they received their implants relatively recently, they might eventually catch up with their hearing peers. Longitudinal studies should further explore the development of emotion regulation and social functioning in cochlear implant children. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
[The development of musicality in children after cochlear implantation].

PubMed

Zheng, Yan; Liu, Bo; Dong, Ruijuan; Xu, Tianqiu; Chen, Jing; Chen, Xuejing; Zhong, Yan; Meng, Chao; Wang, Hong; Chen, Xueqing

2014-08-01

The purpose of this study is to analyze the development of musicality in children after cochlear implantation, and provide a clinical database for the evaluation of their musicality. Twenty-six children with cochlear implants (CI group) participated in this research. They received cochlear implants at the age of 11 to 68 months with a mean of 35.6 months. Seventy-six infants as a control group aged from 1 to 24 months with a mean of 6.1 months participated in this study, whose hearing were considered normal by passing the case history collection, high-risk registers for hearing loss and hearing screening using DPOAE. The music and young children with CIs: Musicality Rating Scale was used to evaluate their musicality. The evaluation was performed before cochlear implantation and 1, 3, 6, 9, 12, 24 months after cochlear implantation for children with cochlear implants. The evaluation was also performed at 1, 3, 6, 9, 12, 24 months for children with normal hearing. The mean scores of musicality showed significant improvements with time of CI use for CI group (P<0.05). The mean scores of musicality also showed significant improvements with time for control group (P<0.05). There were no significant differences in mean scores between CI group and control group at 1, 3, 6, 9, 12 months of hearing age by rank sum test (P>0.05). Significant difference was noted between the two groups at 24 months (P<0.05). The musicality of children with cochlear implants improved significantly with time after cochlear implantation. The most rapid growth was found in the first year after cochlear implantation.
Cochlear Implants:System Design, Integration and Evaluation

PubMed Central

Rebscher, Stephen; Harrison, William V.; Sun, Xiaoan; Feng, Haihong

2009-01-01

As the most successful neural prosthesis, cochlear implants have provided partial hearing to more than 120,000 persons worldwide; half of which being pediatric users who are able to develop nearly normal language. Biomedical engineers have played a central role in the design, integration and evaluation of the cochlear implant system, but the overall success is a result of collaborative work with physiologists, psychologists, physicians, educators, and entrepreneurs. This review presents broad yet in-depth academic and industrial perspectives on the underlying research and ongoing development of cochlear implants. The introduction accounts for major events and advances in cochlear implants, including dynamic interplays among engineers, scientists, physicians, and policy makers. The review takes a system approach to address critical issues from design and specifications to integration and evaluation. First, the cochlear implant system design and specifications are laid out. Second, the design goals, principles, and methods of the subsystem components are identified from the external speech processor and radio frequency transmission link to the internal receiver, stimulator and electrode arrays. Third, system integration and functional evaluation are presented with respect to safety, reliability, and challenges facing the present and future cochlear implant designers and users. Finally, issues beyond cochlear implants are discussed to address treatment options for the entire spectrum of hearing impairment as well as to use the cochlear implant as a model to design and evaluate other similar neural prostheses such as vestibular and retinal implants. PMID:19946565
Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

PubMed

Li, Xu; Mao, Xiao-Bo; Hei, Ren-Yi; Zhang, Zhi-Bin; Wen, Li-Ting; Zhang, Peng-Zhi; Qiu, Jian-Hua; Qiao, Li

2011-01-01

A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL). The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2)S) has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2)S in cochlear blood flow regulation and noise protection. The gene and protein expression of the H(2)S synthetase cystathionine-γ-lyase (CSE) in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP), NaHS or DL-propargylglycine (PPG) were locally administered. Local sodium hydrosulfide (NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR), cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage of OHC loss occurred in the PPG group. Our results suggest that H(2)S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.
Cochlear Patency After Transmastoid Labyrinthectomy for Ménière's Syndrome.

PubMed

Sargent, Eric W; Liao, Eric; Gonda, Roger L

2016-08-01

Labyrinthectomy is considered the "gold standard" in the treatment of intractable vertigo attacks because of Ménière's Disease (MD) but sacrifices all residual hearing. Interest in auditory rehabilitation has lead to cochlear implantation in some patients. Concern remains that the cochlear lumen may fill with tissue or bone after surgery. This study sought to determine the incidence of obliteration of the cochlea after transmastoid labyrinthectomy. Retrospective observational study. Tertiary referral center. Eighteen patients with intractable vertigo from MD who underwent surgery. Transmastoid labyrinthectomy between 2008 and 2013. Cochleas were imaged with unenhanced, heavily T2-weighted magnetic resonance imaging (MRI). Presence of symmetrical cochlear fluid signals on MRI. There was no loss of fluid signal in the cochleas of operated ear compared with the contralateral, unoperated ear in any subject an average of 3 years (standard deviation [SD]: 1.2) after surgery. Five of 18 patients had the vestibule blocked with bone wax at the time of surgery. Blocking the vestibule with bone wax did not change the cochlear fluid signal. The risk of cochlear obstruction after labyrinthectomy for MD is very low. The significance of this finding is that patients with MD who undergo labyrinthectomy will likely remain candidates for cochlear implantation in the labyrinthectomized ear long after surgery if this becomes needed. Immediate cochlear implantation or placement of a cochlear lumen keeper during labyrinthectomy for MD is probably not necessary.
Central Projections of Melanopsin-Expressing Retinal Ganglion Cells in the Mouse

PubMed Central

HATTAR, SAMER; KUMAR, MONICA; PARK, ALEXANDER; TONG, PATRICK; TUNG, JONATHAN; YAU, KING-WAI; BERSON, DAVID M.

2010-01-01

A rare type of ganglion cell in mammalian retina is directly photosensitive. These novel retinal photoreceptors express the photopigment melanopsin. They send axons directly to the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus (OPN), thereby contributing to photic synchronization of circadian rhythms and the pupillary light reflex. Here, we sought to characterize more fully the projections of these cells to the brain. By targeting tau-lacZ to the melanopsin gene locus in mice, ganglion cells that would normally express melanopsin were induced to express, instead, the marker enzyme β-galactosidase. Their axons were visualized by X-gal histochemistry or anti-β-galactosidase immunofluorescence. Established targets were confirmed, including the SCN, IGL, OPN, ventral division of the lateral geniculate nucleus (LGv), and preoptic area, but the overall projections were more widespread than previously recognized. Targets included the lateral nucleus, peri-supraoptic nucleus, and subparaventricular zone of the hypothalamus, medial amygdala, margin of the lateral habenula, posterior limitans nucleus, superior colliculus, and periaqueductal gray. There were also weak projections to the margins of the dorsal lateral geniculate nucleus. Co-staining with the cholera toxin B subunit to label all retinal afferents showed that melanopsin ganglion cells provide most of the retinal input to the SCN, IGL, and lateral habenula and much of that to the OPN, but that other ganglion cells do contribute at least some retinal input to these targets. Staining patterns after monocular enucleation revealed that the projections of these cells are overwhelmingly crossed except for the projection to the SCN, which is bilaterally symmetrical. PMID:16736474
Music mixing preferences of cochlear implant recipients: a pilot study.

PubMed

Buyens, Wim; van Dijk, Bas; Moonen, Marc; Wouters, Jan

2014-05-01

Music perception and appraisal are generally poor in cochlear implant recipients. Simple musical structures, lyrics that are easy to follow, and clear rhythm/beat have been reported among the top factors to enhance music enjoyment. The present study investigated the preference for modified relative instrument levels in music with normal-hearing and cochlear implant subjects. In experiment 1, test subjects were given a mixing console and multi-track recordings to determine their most enjoyable audio mix. In experiment 2, a preference rating experiment based on the preferred relative level settings in experiment 1 was performed. Experiment 1 was performed with four postlingually deafened cochlear implant subjects, experiment 2 with ten normal-hearing and ten cochlear implant subjects. A significant difference in preference rating was found between normal-hearing and cochlear implant subjects. The latter preferred an audio mix with larger vocals-to-instruments ratio. In addition, given an audio mix with clear vocals and attenuated instruments, cochlear implant subjects preferred the bass/drum track to be louder than the other instrument tracks. The original audio mix in real-world music might not be suitable for cochlear implant recipients. Modifying the relative instrument level settings potentially improves music enjoyment.
Betahistine metabolites, aminoethylpyridine, and hydroxyethylpyridine increase cochlear blood flow in guinea pigs in vivo.

PubMed

Bertlich, Mattis; Ihler, Fritz; Sharaf, Kariem; Weiss, Bernhard G; Strupp, Michael; Canis, Martin

2014-10-01

Betahistine is a histamine-like drug that is used in the treatment of Ménière's disease. It is commonly believed that betahistine increases cochlear blood flow and thus decreases the endolymphatic hydrops that is the cause of Ménière's. Despite common clinical use, there is little understanding of the kinetics or effects of its metabolites. This study investigated the effect of the betahistine metabolites aminoethylpyridine, hydroxyethylpyridine, and pyridylacetic acid on cochlear microcirculation. Guinea pigs were randomly assigned to one of the groups: placebo, betahistine, or equimolar amounts of aminoethylpyridine, hydroxyethylpyridine, or pyridylacetic acid. Cochlear blood flow and mean arterial pressure were recorded for three minutes before and 15 minutes after treatment. Thirty Dunkin-Hartley guinea pigs assigned to one of five groups with six guinea pigs per group. Betahistine, aminoethylpyridine, and hydroxyethylpyridine caused a significant increase in cochlear blood flow in comparison to placebo. The effect seen under aminoethylpyridin was greatest. The group treated with pyridylacetic acid showed no significant effect on cochlear blood flow. Aminoethylpyridine and hydroxyethylpyridine are, like betahistine, able to increase cochlear blood flow significantly. The effect of aminoethylpyridine was greatest. Pyridylacetic acid had no effect on cochlear microcirculation.

Histaminergic H3-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow.

PubMed

Bertlich, Mattis; Ihler, Friedrich; Freytag, Saskia; Weiss, Bernhard G; Strupp, Michael; Canis, Martin

2015-01-01

Betahistine is a histamine-like drug that is considered beneficial in Ménière's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H1-receptor and as an inverse agonist at the H3-receptor, these receptors as well as the adrenergic α2-receptor were investigated for betahistine effects on cochlear blood flow. A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H1-, H3- or α2-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. Blockage of the H3- or α2-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H3-receptors caused a drop in cochlear blood flow and blood pressure. H1-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. Betahistine most likely affects cochlear blood flow through histaminergic H3-heteroreceptors. © 2015 S. Karger AG, Basel.
Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow.

PubMed

Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G; Freytag, Saskia; Jakob, Mark; Strupp, Michael; Pellkofer, Hannah; Canis, Martin

2017-09-01

The potential of Fingolimod (FTY-720), a sphingosine-1-phosphate analogue, to revoke the changes in cochlear blood flow induced by tumor necrosis factor (TNF) was investigated. Impairment of cochlear blood flow has often been considered as the common final pathway of various inner ear pathologies. TNF, an ubiquitous cytokine, plays a major role in these pathologies, reducing cochlear blood flow via sphingosine-1-phosphate-signaling. Fifteen Dunkin-Hartley guinea pigs were randomly assigned to one of three groups (placebo/placebo, TNF/placebo, TNF/FTY-720). Cochlear microcirculation was quantified over 60 minutes by in vivo fluorescence microscopy before and after topical application of placebo or TNF (5 ng/ml) and after subsequent application of placebo or FTY-720 (200 μg/ml). Treatment with TNF led to a significant decrease of cochlear blood flow.Following this, application of placebo caused no significant changes while application of FTY-720 caused a significant rise in cochlear blood flow. FTY-720 is capable of reversing changes in cochlear blood flow induced by application of TNF. This makes FTY-720 a valid candidate for potential treatment of numerous inner ear pathologies.
[Cochlear implantation in patients with Waardenburg syndrome type II].

PubMed

Wan, Liangcai; Guo, Menghe; Chen, Shuaijun; Liu, Shuangriu; Chen, Hao; Gong, Jian

2010-05-01

To describe the multi-channel cochlear implantation in patients with Waardenburg syndrome including surgeries, pre and postoperative hearing assessments as well as outcomes of speech recognition. Multi-channel cochlear implantation surgeries have been performed in 12 cases with Waardenburg syndrome type II in our department from 2000 to 2008. All the patients received multi-channel cochlear implantation through transmastoid facial recess approach. The postoperative outcomes of 12 cases were compared with 12 cases with no inner ear malformation as a control group. The electrodes were totally inserted into the cochlear successfully, there was no facial paralysis and cerebrospinal fluid leakage occurred after operation. The hearing threshold in this series were similar to that of the normal cochlear implantation. After more than half a year of speech rehabilitation, the abilities of speech discrimination and spoken language of all the patients were improved compared with that of preoperation. Multi-channel cochlear implantation could be performed in the cases with Waardenburg syndrome, preoperative hearing and images assessments should be done.
[Cochlear implantation through the middle fossa approach].

PubMed

Szyfter, W; Colletti, V; Pruszewicz, A; Kopeć, T; Szymiec, E; Kawczyński, M; Karlik, M

2001-01-01

The inner part of cochlear implant is inserted into inner ear during surgery through mastoid and middle ear. It is a classical method, used in the majority cochlear centers in the world. This is not a suitable method in case of chronic otitis media and middle ear malformation. In these cases Colletti proposed the middle fossa approach and cochlear implant insertion omitting middle ear structures. In patient with bilateral chronic otitis media underwent a few ears operations without obtaining dry postoperative cavity. Cochlear implantation through the middle fossa approach was performed in this patient. The bone fenster was cut, temporal lobe was bent and petrosus pyramid upper surface was exposed. When the superficial petrosal greater nerve, facial nerve and arcuate eminence were localised, the cochlear was open in the basal turn and electrode were inserted. The patient achieves good results in the postoperative speech rehabilitation. It confirmed Colletti tesis that deeper electrode insertion in the cochlear implantation through the middle fossa approach enable use of low and middle frequencies, which are very important in speech understanding.
United Kingdom national paediatric bilateral cochlear implant audit: preliminary results.

PubMed

Cullington, Helen; Bele, Devyanee; Brinton, Julie; Lutman, Mark

2013-11-01

Prior to 2009, United Kingdom (UK) public funding was mainly only available for children to receive unilateral cochlear implants. In 2009, the National Institute for Health and Care Excellence published guidance for cochlear implantation following their review. According to these guidelines, all suitable children are eligible to have simultaneous bilateral cochlear implants or a sequential bilateral cochlear implant if they had received the first before the guidelines were published. Fifteen UK cochlear implant centres formed a consortium to carry out a multi-centre audit. The audit involves collecting data from simultaneously and sequentially implanted children at four intervals: before bilateral cochlear implants or before the sequential implant, 1, 2, and 3 years after bilateral implants. The measures include localization, speech recognition in quiet and background noise, speech production, listening, vocabulary, parental perception, quality of life, and surgical data including complications. The audit has now passed the 2-year point, and data have been received on 850 children. This article provides a first view of some data received up until March 2012.
Ischemia-reperfusion injury of the cochlea: pharmacological strategies for cochlear protection and implications of glutamate and reactive oxygen species.

PubMed

Tabuchi, Keiji; Nishimura, Bungo; Tanaka, Shuho; Hayashi, Kentaro; Hirose, Yuki; Hara, Akira

2010-06-01

A large amount of energy produced by active aerobic metabolism is necessary for the cochlea to maintain its function. This makes the cochlea vulnerable to blockade of cochlear blood flow and interruption of the oxygen supply. Although certain forms of human idiopathic sudden sensorineural hearing loss reportedly arise from ischemic injury, the pathological mechanism of cochlear ischemia-reperfusion injury has not been fully elucidated. Recent animal studies have shed light on the mechanisms of cochlear ischemia-reperfusion injury. It will help in the understanding of the pathology of cochlear ischemia-reperfusion injury to classify this injury into ischemic injury and reperfusion injury. Excitotoxicity, mainly observed during the ischemic period, aggravates the injury of primary auditory neurons. On the other hand, oxidative damage induced by hydroxyl radicals and nitric oxide enhances cochlear reperfusion injury. This article briefly summarizes the generation mechanisms of cochlear ischemia-reperfusion injury and potential therapeutic targets that could be developed for the effective management of this injury type.
Musical ear syndrome in adult cochlear implant patients.

PubMed

Low, W-K; Tham, C A; D'Souza, V-D; Teng, S-W

2013-09-01

Except for a single case report, musical ear syndrome in cochlear implantees has not been studied. We aimed to study the prevalence and nature of musical ear syndrome among adult cochlear implant patients, as well as the effect on their emotional well-being. STUDY DESIGN, PATIENTS AND INTERVENTION: A cross-sectional survey of patients aged 18 years and above who had received cochlear implants for profound hearing loss between 1997 and 2010. Of the 82 patients studied, 18 (22 per cent) were found to have experienced musical ear syndrome. Seven and 11 patients had musical ear syndrome prior to and after cochlear implantation, respectively. The character of musical ear syndrome symptoms was described as instrumental music (n = 2), singing (6) or both (10). Fourteen patients reported an adverse emotional effect, with three expressing ‘intolerance’. In this study, 22 per cent of cochlear implantees experienced musical ear syndrome. These symptoms affected patients’ emotional state, but most coped well. Musical ear syndrome can occur prior to and after cochlear implantation.
Importance of cochlear health for implant function.

PubMed

Pfingst, Bryan E; Zhou, Ning; Colesa, Deborah J; Watts, Melissa M; Strahl, Stefan B; Garadat, Soha N; Schvartz-Leyzac, Kara C; Budenz, Cameron L; Raphael, Yehoash; Zwolan, Teresa A

2015-04-01

Amazing progress has been made in providing useful hearing to hearing-impaired individuals using cochlear implants, but challenges remain. One such challenge is understanding the effects of partial degeneration of the auditory nerve, the target of cochlear implant stimulation. Here we review studies from our human and animal laboratories aimed at characterizing the health of the implanted cochlea and the auditory nerve. We use the data on cochlear and neural health to guide rehabilitation strategies. The data also motivate the development of tissue-engineering procedures to preserve or build a healthy cochlea and improve performance obtained by cochlear implant recipients or eventually replace the need for a cochlear implant. This article is part of a Special Issue entitled . Copyright © 2014 Elsevier B.V. All rights reserved.
The influence of cochlear shape on low-frequency hearing.

PubMed

Manoussaki, Daphne; Chadwick, Richard S; Ketten, Darlene R; Arruda, Julie; Dimitriadis, Emilios K; O'Malley, Jen T

2008-04-22

The conventional theory about the snail shell shape of the mammalian cochlea is that it evolved essentially and perhaps solely to conserve space inside the skull. Recently, a theory proposed that the spiral's graded curvature enhances the cochlea's mechanical response to low frequencies. This article provides a multispecies analysis of cochlear shape to test this theory and demonstrates that the ratio of the radii of curvature from the outermost and innermost turns of the cochlear spiral is a significant cochlear feature that correlates strongly with low-frequency hearing limits. The ratio, which is a measure of curvature gradient, is a reflection of the ability of cochlear curvature to focus acoustic energy at the outer wall of the cochlear canal as the wave propagates toward the apex of the cochlea.
Manipulating cell fate in the cochlea: a feasible therapy for hearing loss

PubMed Central

Fujioka, Masato; Okano, Hideyuki; Edge, Albert SB

2015-01-01

Mammalian auditory hair cells do not spontaneously regenerate, unlike hair cells in lower vertebrates including fish and birds. In mammals, hearing loss due to the loss of hair cells is thus permanent and intractable. Recent studies in the mouse have demonstrated spontaneous hair cell regeneration during a short postnatal period, but this regenerative capacity is lost in the adult cochlea. Reduced regeneration coincides with a transition that results in a decreased pool of progenitor cells in the cochlear sensory epithelium. Here, we review the signaling cascades involved in hair cell formation and morphogenesis of the organ of Corti in developing mammals, the changing status of progenitor cells in the cochlea, and the regeneration of auditory hair cells in adult mammals. PMID:25593106
Physiopathology of the cochlear microcirculation.

PubMed

Shi, Xiaorui

2011-12-01

Normal blood supply to the cochlea is critically important for establishing the endocochlear potential and sustaining production of endolymph. Abnormal cochlear microcirculation has long been considered an etiologic factor in noise-induced hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or vestibular function, and Meniere's disease. Knowledge of the mechanisms underlying the pathophysiology of cochlear microcirculation is of fundamental clinical importance. A better understanding of cochlear blood flow (CoBF) will enable more effective management of hearing disorders resulting from aberrant blood flow. This review focuses on recent discoveries and findings related to the physiopathology of the cochlear microvasculature. Published by Elsevier B.V.
Physiopathology of the Cochlear Microcirculation

PubMed Central

Shi, Xiaorui

2011-01-01

Normal blood supply to the cochlea is critically important for establishing the endocochlear potential and sustaining production of endolymph. Abnormal cochlear microcirculation has long been considered an etiologic factor in noise-induced hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or vestibular function, and Meniere's disease. Knowledge of the mechanisms underlying the pathophysiology of cochlear microcirculation is of fundamental clinical importance. A better understanding of cochlear blood flow (CoBF) will enable more effective management of hearing disorders resulting from aberrant blood flow. This review focuses on recent discoveries and findings related to the physiopathology of the cochlear microvasculature. PMID:21875658
Expression of the proliferation marker Ki-67 during early mouse development.

PubMed

Winking, H; Gerdes, J; Traut, W

2004-01-01

In somatic tissues, the mouse Ki-67 protein (pKi-67) is expressed in proliferating cells only. Depending on the stage of the cell cycle, pKi-67 is associated with different nuclear domains: with euchromatin as part of the perichromosomal layer, with centromeric heterochromatin, and with the nucleolus. In gametes, sex-specific expression is evident. Mature MII oocytes contain pKi-67, whereas pKi-67 is not detectable in mature sperm. We investigated the re-establishment of the cell cycle-dependent distribution of pKi-67 during early mouse development. After fertilization, male and female pronuclei exhibited very little or no pKi-67, while polar bodies were pKi-67 positive. Towards the end of the first cell cycle, prophase chromosomes of male and female pronuclei simultaneously got decorated with pKi-67. In 2-cell embryos, the distribution pattern changed, presumably depending on the progress of development of the embryo, from a distribution all over the nucleus to a preferential location in the nucleolus precursor bodies (NPBs). From the 4-cell stage onwards, pKi-67 showed the regular nuclear relocations known from somatic tissues: during mitosis the protein was found covering the chromosome arms as a constituent of the perichromosomal layer, in early G1 it was distributed in the whole nucleus, and for the rest of the cell cycle it was associated with NPBs or with the nucleolus. Copyright 2004 S. Karger AG, Basel
Modularity in the Organization of Mouse Primary Visual Cortex

PubMed Central

Ji, Weiqing; Gămănuţ, Răzvan; Bista, Pawan; D’Souza, Rinaldo D.; Wang, Quanxin; Burkhalter, Andreas

2015-01-01

SUMMARY Layer 1 (L1) of primary visual cortex (V1) is the target of projections from many brain regions outside of V1. We found that inputs to the non-columnar mouse V1 from the dorsal lateral geniculate nucleus and feedback projections from multiple higher cortical areas to L1 are patchy. The patches are matched to a pattern of M2 muscarinic acetylcholine receptor expression at fixed locations of mouse, rat and monkey V1. Neurons in L2/3 aligned with M2-rich patches have high spatial acuity whereas cells in M2-poor zones exhibited high temporal acuity. Together M2+ and M2− zones form constant-size domains that are repeated across V1. Domains map subregions of the receptive field, such that multiple copies are contained within the point image. The results suggest that the modular network in mouse V1 selects spatiotemporally distinct clusters of neurons within the point image for top-down control and differential routing of inputs to cortical streams. PMID:26247867
Working memory in Farsi-speaking children with normal development and cochlear implant.

PubMed

Soleymani, Zahra; Amidfar, Meysam; Dadgar, Hooshang; Jalaie, Shohre

2014-04-01

Working memory has an important role in language acquisition and development of cognition skills. The ability of encoding, storage and retrieval of phonological codes, as activities of working memory, acquired by audition sense. Children with cochlear implant experience a period that they are not able to perceive sounds. In order to assess the effect of hearing on working memory, we investigated working memory as a cognition skill in children with normal development and cochlear implant. Fifty students with normal hearing and 50 students with cochlear implant aged 5-7 years participated in this study. Children educated in the preschool, the first and second grades. Children with normal development were matched based on age, gender, and grade of education with cochlear implant. Two components of working memory including phonological loop and central executive were compared between two groups. Phonological loop assessed by nonword repetition task and forward digit span. To assess central executive component backward digit span was used. The developmental trend was studied in children with normal development and cochlear implant as well. The effect of age at implantation in children with cochlear implants on components of working memory was investigated. There are significant differences between children with normal development and cochlear implant in all tasks that assess working memory (p < 0.001). The children's age at implantation was negatively correlated with all tasks (p < 0.001). In contrast, duration of usage of cochlear implant set was positively correlated with all tasks (p < 0.001). The comparison of working memory between different grades showed significant differences both in children with normal development and in children with cochlear implant (p < 0.05). These results implied that children with cochlear implant may experience difficulties in working memory. Therefore, these children have problems in encoding, practicing, and repeating phonological units. The results also suggested working memory develops when the child grows up. In cochlear implant children, with decreasing age at implantation and increasing their experience in perceiving sound, working memory skills improved. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Adenosine receptors regulate susceptibility to noise-induced neural injury in the mouse cochlea and hearing loss.

PubMed

Vlajkovic, Srdjan M; Ambepitiya, Kaushi; Barclay, Meagan; Boison, Detlev; Housley, Gary D; Thorne, Peter R

2017-03-01

Our previous studies have shown that the stimulation of A 1 adenosine receptors in the inner ear can mitigate the loss of sensory hair cells and hearing loss caused by exposure to traumatic noise. Here, we focus on the role of adenosine receptors (AR) in the development of noise-induced neural injury in the cochlea using A 1 AR and A 2A AR null mice (A 1 AR -/- and A 2A AR -/- ). Wildtype (WT) and AR deficient mice were exposed to octave band noise (8-16 kHz, 100 dB SPL) for 2 h to induce cochlear injury and hearing loss. Auditory thresholds and input/output functions were assessed using auditory brainstem responses (ABR) before and two weeks post-exposure. The loss of outer hair cells (OHC), afferent synapses and spiral ganglion neurons (SGN) were assessed by quantitative histology. A 1 AR -/- mice (6-8 weeks old) displayed a high frequency hearing loss (ABR threshold shift and reduced ABR wave I and II amplitudes). This hearing loss was further aggravated by acute noise exposure and exceeded the hearing loss in the WT and A 2A AR -/- mice. All mice experienced the loss of OHC, synaptic ribbons and SGN after noise exposure, but the loss of SGN was significantly higher in A 1 AR -/- mice than in the A 2A AR -/- and WT genotypes. The A 2A AR -/- demonstrated better preservation of OHC and afferent synapses and the minimal loss of SGN after noise exposure. The findings suggest that the loss of A 1 AR expression results in an increased susceptibility to cochlear neural injury and hearing loss, whilst absence of A 2A AR increases cochlear resistance to acoustic trauma. Copyright © 2016 Elsevier B.V. All rights reserved.
Role of Neuropilin-1/Semaphorin-3A signaling in the functional and morphological integrity of the cochlea

PubMed Central

Salehi, Pezhman; Gundimeda, Usha; Lael Cantu, Homero; Lavinsky, Joel; Myint, Anthony; Wang, Juemei; Abdala, Carolina; Ohyama, Takahiro; Coate, Thomas Matthew

2017-01-01

Neuropilin-1 (Nrp1) encodes the transmembrane cellular receptor neuropilin-1, which is associated with cardiovascular and neuronal development and was within the peak SNP interval on chromosome 8 in our prior GWAS study on age-related hearing loss (ARHL) in mice. In this study, we generated and characterized an inner ear-specific Nrp1 conditional knockout (CKO) mouse line because Nrp1 constitutive knockouts are embryonic lethal. In situ hybridization demonstrated weak Nrp1 mRNA expression late in embryonic cochlear development, but increased expression in early postnatal stages when cochlear hair cell innervation patterns have been shown to mature. At postnatal day 5, Nrp1 CKO mice showed disorganized outer spiral bundles and enlarged microvessels of the stria vascularis (SV) but normal spiral ganglion cell (SGN) density and presynaptic ribbon body counts; however, we observed enlarged SV microvessels, reduced SGN density, and a reduction of presynaptic ribbons in the outer hair cell region of 4-month-old Nrp1 CKO mice. In addition, we demonstrated elevated hearing thresholds of the 2-month-old and 4-month-old Nrp1 CKO mice at frequencies ranging from 4 to 32kHz when compared to 2-month-old mice. These data suggest that conditional loss of Nrp1 in the inner ear leads to progressive hearing loss in mice. We also demonstrated that mice with a truncated variant of Nrp1 show cochlear axon guidance defects and that exogenous semaphorin-3A, a known neuropilin-1 receptor agonist, repels SGN axons in vitro. These data suggest that Neuropilin-1/Semaphorin-3A signaling may also serve a role in neuronal pathfinding in the developing cochlea. In summary, our results here support a model whereby Neuropilin-1/Semaphorin-3A signaling is critical for the functional and morphological integrity of the cochlea and that Nrp1 may play a role in ARHL. PMID:29059194
Lack of financial barriers to pediatric cochlear implantation: impact of socioeconomic status on access and outcomes.

PubMed

Chang, David T; Ko, Alvin B; Murray, Gail S; Arnold, James E; Megerian, Cliff A

2010-07-01

(1) To analyze if socioeconomic status influences access to cochlear implantation in an environment with adequate Medicaid reimbursement. (2) To determine the impact of socioeconomic status on outcomes after unilateral cochlear implantation. Retrospective cohort study. University Hospitals Case Medical Center and Rainbow Babies and Children's Hospital (tertiary referral center), Cleveland, Ohio. Pediatric patients (age range, newborn to 18 years) who received unilateral cochlear implantation during the period 1996 to 2008. Access to cochlear implantation after referral to a cochlear implant center, postoperative complications, compliance with follow-up appointments, and access to sequential bilateral cochlear implantation. A total of 133 pediatric patients were included in this study; 64 were Medicaid-insured patients and 69 were privately insured patients. There was no statistical difference in the odds of initial cochlear implantation, age at referral, or age at implantation between the 2 groups. The odds of prelingual Medicaid-insured patients receiving sequential bilateral cochlear implantation was less than half that of the privately insured group (odds ratio [OR], 0.43; P = .03). The odds of complications in Medicaid-insured children were almost 5-fold greater than the odds for privately insured children (OR, 4.6; P = .03). There were 10 complications in 51 Medicaid-insured patients (19.6%) as opposed to 3 in 61 privately insured patients (4.9%). Medicaid-insured patients missed substantially more follow-up appointments overall (35% vs 23%) and more consecutive visits (1.9 vs 1.1) compared with privately insured patients. In an environment with adequate Medicaid reimbursement, eligible children have equal access to cochlear implantation, regardless of socioeconomic background. However, lower socioeconomic background is associated with higher rates of postoperative complications, worse follow-up compliance, and lower rates of sequential bilateral implantation, observed herein in Medicaid-insured patients. These findings present opportunities for cochlear implant centers to create programs to address such downstream disparities.
Benefit and predictive factors for speech perception outcomes in pediatric bilateral cochlear implant recipients.

PubMed

Chang, Young-Soo; Hong, Sung Hwa; Kim, Eun Yeon; Choi, Ji Eun; Chung, Won-Ho; Cho, Yang-Sun; Moon, Il Joon

2018-05-18

Despite recent advancement in the prediction of cochlear implant outcome, the benefit of bilateral procedures compared to bimodal stimulation and how we predict speech perception outcomes of sequential bilateral cochlear implant based on bimodal auditory performance in children remain unclear. This investigation was performed: (1) to determine the benefit of sequential bilateral cochlear implant and (2) to identify the associated factors for the outcome of sequential bilateral cochlear implant. Observational and retrospective study. We retrospectively analyzed 29 patients with sequential cochlear implant following bimodal-fitting condition. Audiological evaluations were performed; the categories of auditory performance scores, speech perception with monosyllable and disyllables words, and the Korean version of Ling. Audiological evaluations were performed before sequential cochlear implant with the bimodal fitting condition (CI1+HA) and one year after the sequential cochlear implant with bilateral cochlear implant condition (CI1+CI2). The good Performance Group (GP) was defined as follows; 90% or higher in monosyllable and bisyllable tests with auditory-only condition or 20% or higher improvement of the scores with CI1+CI2. Age at first implantation, inter-implant interval, categories of auditory performance score, and various comorbidities were analyzed by logistic regression analysis. Compared to the CI1+HA, CI1+CI2 provided significant benefit in categories of auditory performance, speech perception, and Korean version of Ling results. Preoperative categories of auditory performance scores were the only associated factor for being GP (odds ratio=4.38, 95% confidence interval - 95%=1.07-17.93, p=0.04). The children with limited language development in bimodal condition should be considered as the sequential bilateral cochlear implant and preoperative categories of auditory performance score could be used as the predictor in speech perception after sequential cochlear implant. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.
A comparison of speech intonation production and perception abilities of Farsi speaking cochlear implanted and normal hearing children.

PubMed

Moein, Narges; Khoddami, Seyyedeh Maryam; Shahbodaghi, Mohammad Rahim

2017-10-01

Cochlear implant prosthesis facilitates spoken language development and speech comprehension in children with severe-profound hearing loss. However, this prosthesis is limited in encoding information about fundamental frequency and pitch that are essentially for recognition of speech prosody. The purpose of the present study is to investigate the perception and production of intonation in cochlear implant children and comparison with normal hearing children. This study carried out on 25 cochlear implanted children and 50 children with normal hearing. First, using 10 action pictures statements and questions sentences were extracted. Fundamental frequency and pitch changes were identified using Praat software. Then, these sentences were judged by 7 adult listeners. In second stage 20 sentences were played for child and he/she determined whether it was in a question form or statement one. Performance of cochlear implanted children in perception and production of intonation was significantly lower than children with normal hearing. The difference between fundamental frequency and pitch changes in cochlear implanted children and children with normal hearing was significant (P < 0/05). Cochlear implanted children performance in perception and production of intonation has significant correlation with child's age surgery and duration of prosthesis use (P < 0/05). The findings of the current study show that cochlear prostheses have limited application in facilitating the perception and production of intonation in cochlear implanted children. It should be noted that the child's age at the surgery and duration of prosthesis's use is important in reduction of this limitation. According to these findings, speech and language pathologists should consider intervention of intonation in treatment program of cochlear implanted children. Copyright © 2017 Elsevier B.V. All rights reserved.

The Role of MRI in Diagnosing Neurovascular Compression of the Cochlear Nerve Resulting in Typewriter Tinnitus.

PubMed

Bae, Y J; Jeon, Y J; Choi, B S; Koo, J-W; Song, J-J

2017-06-01

Typewriter tinnitus, a symptom characterized by paroxysmal attacks of staccato sounds, has been thought to be caused by neurovascular compression of the cochlear nerve, but the correlation between radiologic evidence of neurovascular compression of the cochlear nerve and symptom presentation has not been thoroughly investigated. The purpose of this study was to examine whether radiologic evidence of neurovascular compression of the cochlear nerve is pathognomonic in typewriter tinnitus. Fifteen carbamazepine-responding patients with typewriter tinnitus and 8 control subjects were evaluated with a 3D T2-weighted volume isotropic turbo spin-echo acquisition sequence. Groups 1 (16 symptomatic sides), 2 (14 asymptomatic sides), and 3 (16 control sides) were compared with regard to the anatomic relation between the vascular loop and the internal auditory canal and the presence of neurovascular compression of the cochlear nerve with/without angulation/indentation. The anatomic location of the vascular loop was not significantly different among the 3 groups (all, P > .05). Meanwhile, neurovascular compression of the cochlear nerve on MR imaging was significantly higher in group 1 than in group 3 ( P = .032). However, considerable false-positive (no symptoms with neurovascular compression of the cochlear nerve on MR imaging) and false-negative (typewriter tinnitus without demonstrable neurovascular compression of the cochlear nerve) findings were also observed. Neurovascular compression of the cochlear nerve was more frequently detected on the symptomatic side of patients with typewriter tinnitus compared with the asymptomatic side of these patients or on both sides of control subjects on MR imaging. However, considering false-positive and false-negative findings, meticulous history-taking and the response to the initial carbamazepine trial should be regarded as more reliable diagnostic clues than radiologic evidence of neurovascular compression of the cochlear nerve. © 2017 by American Journal of Neuroradiology.
Sexual Dimorphism in the Brain of the Monogamous California Mouse (Peromyscus californicus).

PubMed

Campi, Katharine L; Jameson, Chelsea E; Trainor, Brian C

2013-01-01

Sex differences in behavior and morphology are usually assumed to be stronger in polygynous species compared to monogamous species. A few brain structures have been identified as sexually dimorphic in polygynous rodent species, but it is less clear whether these differences persist in monogamous species. California mice are among the 5% or less of mammals that are considered to be monogamous and as such provide an ideal model to examine sexual dimorphism in neuroanatomy. In the present study we compared the volume of hypothalamic- and limbic-associated regions in female and male California mice for sexual dimorphism. We also used tyrosine hydroxylase (TH) immunohistochemistry to compare the number of dopamine neurons in the ventral tegmental area (VTA) in female and male California mice. Additionally, tract tracing was used to accurately delineate the boundaries of the VTA. The total volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA), the principal nucleus of the bed nucleus of the stria terminalis (BNST), and the posterodorsal medial amygdala (MEA) was larger in males compared to females. In the SDN-POA we found that the magnitude of sex differences in the California mouse were intermediate between the large differences observed in promiscuous meadow voles and rats and the absence of significant differences in monogamous prairie voles. However, the magnitude of sex differences in MEA and the BNST were comparable to polygynous species. No sex differences were observed in the volume of the whole brain, the VTA, the nucleus accumbens or the number of TH-ir neurons in the VTA. These data show that despite a monogamous social organization, sexual dimorphisms that have been reported in polygynous rodents extend to California mice. Our data suggest that sex differences in brain structures such as the SDN-POA persist across species with different social organizations and may be an evolutionarily conserved characteristic of mammalian brains.
Trends in cochlear implants.

PubMed

Zeng, Fan-Gang

2004-01-01

More than 60,000 people worldwide use cochlear implants as a means to restore functional hearing. Although individual performance variability is still high, an average implant user can talk on the phone in a quiet environment. Cochlear-implant research has also matured as a field, as evidenced by the exponential growth in both the patient population and scientific publication. The present report examines current issues related to audiologic, clinical, engineering, anatomic, and physiologic aspects of cochlear implants, focusing on their psychophysical, speech, music, and cognitive performance. This report also forecasts clinical and research trends related to presurgical evaluation, fitting protocols, signal processing, and postsurgical rehabilitation in cochlear implants. Finally, a future landscape in amplification is presented that requires a unique, yet complementary, contribution from hearing aids, middle ear implants, and cochlear implants to achieve a total solution to the entire spectrum of hearing loss treatment and management.
Comparison of Social Interaction between Cochlear-Implanted Children with Normal Intelligence Undergoing Auditory Verbal Therapy and Normal-Hearing Children: A Pilot Study.

PubMed

Monshizadeh, Leila; Vameghi, Roshanak; Sajedi, Firoozeh; Yadegari, Fariba; Hashemi, Seyed Basir; Kirchem, Petra; Kasbi, Fatemeh

2018-04-01

A cochlear implant is a device that helps hearing-impaired children by transmitting sound signals to the brain and helping them improve their speech, language, and social interaction. Although various studies have investigated the different aspects of speech perception and language acquisition in cochlear-implanted children, little is known about their social skills, particularly Persian-speaking cochlear-implanted children. Considering the growing number of cochlear implants being performed in Iran and the increasing importance of developing near-normal social skills as one of the ultimate goals of cochlear implantation, this study was performed to compare the social interaction between Iranian cochlear-implanted children who have undergone rehabilitation (auditory verbal therapy) after surgery and normal-hearing children. This descriptive-analytical study compared the social interaction level of 30 children with normal hearing and 30 with cochlear implants who were conveniently selected. The Raven test was administered to the both groups to ensure normal intelligence quotient. The social interaction status of both groups was evaluated using the Vineland Adaptive Behavior Scale, and statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 21. After controlling age as a covariate variable, no significant difference was observed between the social interaction scores of both the groups (p > 0.05). In addition, social interaction had no correlation with sex in either group. Cochlear implantation followed by auditory verbal rehabilitation helps children with sensorineural hearing loss to have normal social interactions, regardless of their sex.
Effects of residual hearing on cochlear implant outcomes in children: A systematic-review.

PubMed

Chiossi, Julia Santos Costa; Hyppolito, Miguel Angelo

2017-09-01

to investigate if preoperative residual hearing in prelingually deafened children can interfere on cochlear implant indication and outcomes. a systematic-review was conducted in five international databases up to November-2016, to locate articles that evaluated cochlear implantation in children with some degree of preoperative residual hearing. Outcomes were auditory, language and cognition performances after cochlear implant. The quality of the studies was assessed and classified according to the Oxford Levels of Evidence table - 2011. Risk of biases were also described. From the 30 articles reviewed, two types of questions were identified: (a) what are the benefits of cochlear implantation in children with residual hearing? (b) is the preoperative residual hearing a predictor of cochlear implant outcome? Studies ranged from 04 to 188 subjects, evaluating populations between 1.8 and 10.3 years old. The definition of residual hearing varied between studies. The majority of articles (n = 22) evaluated speech perception as the outcome and 14 also assessed language and speech production. There is evidence that cochlear implant is beneficial to children with residual hearing. Preoperative residual hearing seems to be valuable to predict speech perception outcomes after cochlear implantation, even though the mechanism of how it happens is not clear. More extensive researches must be conducted in order to make recommendations and to set prognosis for cochlear implants based on children preoperative residual hearing. Copyright © 2017 Elsevier B.V. All rights reserved.
Concentration-jump analysis of voltage-dependent conductances activated by glutamate and kainate in neurons of the avian cochlear nucleus.

PubMed Central

Raman, I M; Trussell, L O

1995-01-01

We have examined the mechanisms underlying the voltage sensitivity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors in voltage-clamped outside-out patches and whole cells taken from the nucleus magnocellularis of the chick. Responses to either glutamate or kainate had outwardly rectifying current-voltage relations. The rate and extent of desensitization during prolonged exposure to agonist, and the rate of deactivation after brief exposure to agonist, decreased at positive potentials, suggesting that a kinetic transition was sensitive to membrane potential. Voltage dependence of the peak conductance and of the deactivation kinetics persisted when desensitization was reduced with aniracetam or blocked with cyclothiazide. Furthermore, the rate of recovery from desensitization to glutamate was not voltage dependent. Upon reduction of extracellular divalent cation concentration, kainate-evoked currents increased but preserved rectifying current-voltage relations. Rectification was strongest at lower kainate concentrations. Surprisingly, nonstationary variance analysis of desensitizing responses to glutamate or of the current deactivation after kainate removal revealed an increase in the mean single-channel conductance with more positive membrane potentials. These data indicate that the rectification of the peak response to a high agonist concentration reflects an increase in channel conductance, whereas rectification of steady-state current is dominated by voltage-sensitive channel kinetics. Images FIGURE 2 FIGURE 3 PMID:8580330
Development of N-Methyl-D-Aspartate Receptor Subunits in Avian Auditory Brainstem

PubMed Central

TANG, YE-ZHONG; CARR, CATHERINE E.

2012-01-01

N-methyl-D-aspartate (NMDA) receptor subunit-specific probes were used to characterize developmental changes in the distribution of excitatory amino acid receptors in the chicken’s auditory brainstem nuclei. Although NR1 subunit expression does not change greatly during the development of the cochlear nuclei in the chicken (Tang and Carr [2004] Hear. Res 191:79 – 89), there are significant developmental changes in NR2 subunit expression. We used in situ hybridization against NR1, NR2A, NR2B, NR2C, and NR2D to compare NR1 and NR2 expression during development. All five NMDA subunits were expressed in the auditory brainstem before embryonic day (E) 10, when electrical activity and synaptic responses appear in the nucleus magnocellularis (NM) and the nucleus laminaris (NL). At this time, the dominant form of the receptor appeared to contain NR1 and NR2B. NR2A appeared to replace NR2B by E14, a time that coincides with synaptic refinement and evoked auditory responses. NR2C did not change greatly during auditory development, whereas NR2D increased from E10 and remained at fairly high levels into adulthood. Thus changes in NMDA NR2 receptor subunits may contribute to the development of auditory brainstem responses in the chick. PMID:17366608
Effect of Stimulation Rate on Cochlear Implant Users’ Phoneme, Word and Sentence Recognition in Quiet and in Noise

PubMed Central

Shannon, Robert V.; Cruz, Rachel J.; Galvin, John J.

2011-01-01

High stimulation rates in cochlear implants (CI) offer better temporal sampling, can induce stochastic-like firing of auditory neurons and can increase the electric dynamic range, all of which could improve CI speech performance. While commercial CI have employed increasingly high stimulation rates, no clear or consistent advantage has been shown for high rates. In this study, speech recognition was acutely measured with experimental processors in 7 CI subjects (Clarion CII users). The stimulation rate varied between (approx.) 600 and 4800 pulses per second per electrode (ppse) and the number of active electrodes varied between 4 and 16. Vowel, consonant, consonant-nucleus-consonant word and IEEE sentence recognition was acutely measured in quiet and in steady noise (+10 dB signal-to-noise ratio). Subjective quality ratings were obtained for each of the experimental processors in quiet and in noise. Except for a small difference for vowel recognition in quiet, there were no significant differences in performance among the experimental stimulation rates for any of the speech measures. There was also a small but significant increase in subjective quality rating as stimulation rates increased from 1200 to 2400 ppse in noise. Consistent with previous studies, performance significantly improved as the number of electrodes was increased from 4 to 8, but no significant difference showed between 8, 12 and 16 electrodes. Altogether, there was little-to-no advantage of high stimulation rates in quiet or in noise, at least for the present speech tests and conditions. PMID:20639631
Frequency specificity and left-ear advantage of medial olivocochlear efferent modulation: a study based on stimulus frequency otoacoustic emission.

PubMed

Xing, Dongjia; Gong, Qin

2017-09-06

The medial olivocochlear (MOC) bundle is an auditory nucleus that projects efferent nerve fibers to the outer hair cells (OHCs) for synaptic innervation. The aim of the present study was to investigate the possible existence of frequency and ear specificity in MOC efferent modulation, as well as how MOC activation influences cochlear tuning. Stimulus frequency otoacoustic emissions (SFOAEs) were used to study MOC efferent modulation. Therefore, the current experiment was designed to compare the degree of SFOAE suppression in the both ears of 20 individuals at 1, 2, 4, and 8 kHz. We also compared changes in Q10 values of SFOAE suppression tuning curves at 1, 2, and 4 kHz under contralateral acoustic stimulation (CAS) and no-CAS conditions. We observed a significant reduction in SFOAE magnitude in the CAS condition compared with the no-CAS condition at 1 and 2 kHz in the left ear. A significant difference in CAS suppression was also found between the left and right ears at 1 and 2 kHz, with larger CAS suppression in the left ear. CAS further produced a statistically significant increase in the Q10 value at 1 kHz and a significant reduction in Q10 values at 2 and 4 kHz. These findings suggest a left-ear advantage in terms of CAS-induced MOC efferent SFOAE suppression, with larger MOC efferent modulation for lower frequencies, and cochlear tuning was sharpened by means of MOC activation at lower frequencies and broadened at higher frequencies.
Comparison of temporal properties of auditory single units in response to cochlear infrared laser stimulation recorded with multi-channel and single tungsten electrodes

NASA Astrophysics Data System (ADS)

Tan, Xiaodong; Xia, Nan; Young, Hunter; Richter, Claus-Peter

2015-02-01

Auditory prostheses may benefit from Infrared Neural Stimulation (INS) because optical stimulation allows for spatially selective activation of neuron populations. Selective activation of neurons in the cochlear spiral ganglion can be determined in the central nucleus of the inferior colliculus (ICC) because the tonotopic organization of frequencies in the cochlea is maintained throughout the auditory pathway. The activation profile of INS is well represented in the ICC by multichannel electrodes (MCEs). To characterize single unit properties in response to INS, however, single tungsten electrodes (STEs) should be used because of its better signal-to-noise ratio. In this study, we compared the temporal properties of ICC single units recorded with MCEs and STEs in order to characterize the response properties of single auditory neurons in response to INS in guinea pigs. The length along the cochlea stimulated with infrared radiation corresponded to a frequency range of about 0.6 octaves, similar to that recorded with STEs. The temporal properties of single units recorded with MCEs showed higher maximum rates, shorter latencies, and higher firing efficiencies compared to those recorded with STEs. When the preset amplitude threshold for triggering MCE recordings was raised to twice over the noise level, the temporal properties of the single units became similar to those obtained with STEs. Undistinguishable neural activities from multiple sources in MCE recordings could be responsible for the response property difference between MCEs and STEs. Thus, caution should be taken in single unit recordings with MCEs.
Auditory hair cell centrioles undergo confined Brownian motion throughout the developmental migration of the kinocilium.

PubMed

Lepelletier, Léa; de Monvel, Jacques Boutet; Buisson, Johanna; Desdouets, Chantal; Petit, Christine

2013-07-02

Planar polarization of the forming hair bundle, the mechanosensory antenna of auditory hair cells, depends on the poorly characterized center-to-edge displacement of a primary cilium, the kinocilium, at their apical surface. Taking advantage of the gradient of hair cell differentiation along the cochlea, we reconstituted a map of the kinocilia displacements in the mouse embryonic cochlea. We then developed a cochlear organotypic culture and video-microscopy approach to monitor the movements of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their equilibrium positions, under the apparent constraint of a radial restoring force of ∼0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles' confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.
SOBP Is Mutated in Syndromic and Nonsyndromic Intellectual Disability and Is Highly Expressed in the Brain Limbic System

PubMed Central

Birk, Efrat; Har-Zahav, Adi; Manzini, Chiara M.; Pasmanik-Chor, Metsada; Kornreich, Liora; Walsh, Christopher A.; Noben-Trauth, Konrad; Albin, Adi; Simon, Amos J.; Colleaux, Laurence; Morad, Yair; Rainshtein, Limor; Tischfield, David J.; Wang, Peter; Magal, Nurit; Maya, Idit; Shoshani, Noa; Rechavi, Gideon; Gothelf, Doron; Maydan, Gal; Shohat, Mordechai; Basel-Vanagaite, Lina

2010-01-01

Intellectual disability (ID) affects 1%–3% of the general population. We recently reported on a family with autosomal-recessive mental retardation with anterior maxillary protrusion and strabismus (MRAMS) syndrome. One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis. We report on the identification of a truncating mutation in the SOBP that is responsible for causing both syndromic and nonsyndromic ID in the same family. The protein encoded by the SOBP, sine oculis binding protein ortholog, is a nuclear zinc finger protein. In mice, Sobp (also known as Jxc1) is critical for patterning of the organ of Corti; one of our patients has a subclinical cochlear hearing loss but no gross cochlear abnormalities. In situ RNA expression studies in postnatal mouse brain showed strong expression in the limbic system at the time interval of active synaptogenesis. The limbic system regulates learning, memory, and affective behavior, but limbic circuitry expression of other genes mutated in ID is unusual. By comparing the protein content of the +/jc to jc/jc mice brains with the use of proteomics, we detected 24 proteins with greater than 1.5-fold differences in expression, including two interacting proteins, dynamin and pacsin1. This study shows mutated SOBP involvement in syndromic and nonsyndromic ID with psychosis in humans. PMID:21035105
The role of N-methyl-D-aspartate receptors and nitric oxide in cochlear dopamine release.

PubMed

Halmos, G; Horváth, T; Polony, G; Fekete, A; Kittel, A; Vizi, E S; van der Laan, B F A M; Zelles, T; Lendvai, B

2008-06-23

Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [3H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 muM significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA.
Auditory Hair Cell Centrioles Undergo Confined Brownian Motion Throughout the Developmental Migration of the Kinocilium

PubMed Central

Lepelletier, Léa; de Monvel, Jacques Boutet; Buisson, Johanna; Desdouets, Chantal; Petit, Christine

2013-01-01

Planar polarization of the forming hair bundle, the mechanosensory antenna of auditory hair cells, depends on the poorly characterized center-to-edge displacement of a primary cilium, the kinocilium, at their apical surface. Taking advantage of the gradient of hair cell differentiation along the cochlea, we reconstituted a map of the kinocilia displacements in the mouse embryonic cochlea. We then developed a cochlear organotypic culture and video-microscopy approach to monitor the movements of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their equilibrium positions, under the apparent constraint of a radial restoring force of ∼0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles’ confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them. PMID:23823223
Ultrastructural Morphology of Sperm from Human Globozoospermia

PubMed Central

Ricci, Giuseppe; Andolfi, Laura; Luppi, Stefania; Boscolo, Rita; Zweyer, Marina; Trevisan, Elisa

2015-01-01

Globozoospermia is a rare disorder characterized by the presence of sperm with round head, lacking acrosome. Coiling tail around the nucleus has been reported since early human studies, but no specific significance has conferred it. By contrast, studies on animal models suggest that coiling tail around the nucleus could represent a crucial step of defective spermatogenesis, resulting in round-headed sperm. No observations, so far, support the transfer of this hypothesis to human globozoospermia. The purpose of this work was to compare ultrastructural morphology of human and mouse model globozoospermic sperm. Sperm have been investigated by using scanning and transmission electron microscopy. The images that we obtained show significant similarities to those described in GOPC knockout mice, an animal model of globozoospermia. By using this model as reference, we were able to identify the probable steps of the tail coiling process in human globozoospermia. Although we have no evidence that there is the same pathophysiology in man and knocked-out mouse, the similarities between these ultrastructural observations in human and those in the experimental model are very suggestive. This is the first demonstration of the existence of relevant morphological homologies between the tail coiling in animal model and human globozoospermia. PMID:26436098
Use of suprathreshold stochastic resonance in cochlear implant coding

NASA Astrophysics Data System (ADS)

Allingham, David; Stocks, Nigel G.; Morse, Robert P.

2003-05-01

In this article we discuss the possible use of a novel form of stochastic resonance, termed suprathreshold stochastic resonance (SSR), to improve signal encoding/transmission in cochlear implants. A model, based on the leaky-integrate-and-fire (LIF) neuron, has been developed from physiological data and use to model information flow in a population of cochlear nerve fibers. It is demonstrated that information flow can, in principle, be enhanced by the SSR effect. Furthermore, SSR was found to enhance information transmission for signal parameters that are commonly encountered in cochlear implants. This, therefore, gives hope that SSR may be implemented in cochlear implants to improve speech comprehension.
The Role of Zic Genes in Inner Ear Development in the Mouse: Exploring Mutant Mouse Phenotypes

PubMed Central

Chervenak, Andrew P.; Bank, Lisa M.; Thomsen, Nicole; Glanville-Jones, Hannah C; Skibo, Jonathan; Millen, Kathleen J.; Arkell, Ruth M.; Barald, Kate F.

2014-01-01

Background Murine Zic genes (Zic1-5) are expressed in the dorsal hindbrain and in periotic mesenchyme (POM) adjacent to the developing inner ear. Zic genes are involved in developmental signaling pathways in many organ systems, including the ear, although their exact roles haven't been fully elucidated. This report examines the role of Zic1, Zic2, and Zic4 during inner ear development in mouse mutants in which these Zic genes are affected Results Zic1/Zic4 double mutants don't exhibit any apparent defects in inner ear morphology. By contrast, inner ears from Zic2kd/kd and Zic2Ku/Ku mutants have severe but variable morphological defects in endolymphatic duct/sac and semicircular canal formation and in cochlear extension in the inner ear. Analysis of otocyst patterning in the Zic2Ku/Ku mutants by in situ hybridization showed changes in the expression patterns of Gbx2 and Pax2. Conclusions The experiments provide the first genetic evidence that the Zic genes are required for morphogenesis of the inner ear. Zic2 loss-of-function doesn't prevent initial otocyst patterning but leads to molecular abnormalities concomitant with morphogenesis of the endolymphatic duct. Functional hearing deficits often accompany inner ear dysmorphologies, making Zic2 a novel candidate gene for ongoing efforts to identify the genetic basis of human hearing loss. PMID:25178196
Concomitant differentiation of a population of mouse embryonic stem cells into neuron-like cells and Schwann cell-like cells in a slow-flow microfluidic device

PubMed Central

Ramamurthy, Poornapriya; White, Joshua B.; Park, Joong Yull; Hume, Richard I.; Ebisu, Fumi; Mendez, Flor; Takayama, Shuichi; Barald, Kate F

2016-01-01

Background To send meaningful information to the brain, an inner ear cochlear implant (CI) must become closely coupled to as large and healthy a population of remaining Spiral Ganglion Neurons (SGN) as possible. Inner ear gangliogenesis depends on macrophage migration inhibitory factor (MIF), a directionally attractant neurotrophic cytokine made by both Schwann and supporting cells (Bank et al., 2012). MIF-induced mouse embryonic stem cell (mESC)-derived “neurons” could potentially substitute for lost or damaged SGN. mESC-derived “Schwann cells” produce MIF as do all Schwann cells (Huang et al., 2002; Roth et al., 2007, 2008) and could attract SGN to “ cell coated” implant. Results Neuron- and Schwann cell-like cells were produced from a common population of mESC in an ultra-slow flow microfluidic device. As the populations interacted; “neurons” grew over the “Schwann cell” lawn and early events in myelination were documented. Blocking MIF on the Schwann cell side greatly reduced directional neurite outgrowth. MIF-expressing “Schwann cells” were used to “coat” a CI: mouse SGN and MIF-induced “neurons” grew directionally to the CI and to a wild type but not MIF-knock out Organ of Corti explant. Conclusions Two novel stem cell-based approaches for treating the problem of sensorineural hearing loss are described. PMID:27761977
Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure.

PubMed

Suzuki, Jun; Corfas, Gabriel; Liberman, M Charles

2016-04-25

In acquired sensorineural hearing loss, such as that produced by noise or aging, there can be massive loss of the synaptic connections between cochlear sensory cells and primary sensory neurons, without loss of the sensory cells themselves. Because the cell bodies and central projections of these cochlear neurons survive for months to years, there is a long therapeutic window in which to re-establish functional connections and improve hearing ability. Here we show in noise-exposed mice that local delivery of neurotrophin-3 (NT-3) to the round window niche, 24 hours after an exposure that causes an immediate loss of up to 50% loss of synapses in the cochlear basal region, can regenerate pre- and post-synaptic elements at the hair cell / cochlear nerve interface. This synaptic regeneration, as documented by confocal microscopy of immunostained cochlear sensory epithelia, was coupled with a corresponding functional recovery, as seen in the suprathreshold amplitude of auditory brainstem response Wave 1. Cochlear delivery of neurotrophins in humans is likely achievable as an office procedure via transtympanic injection, making our results highly significant in a translational context.
Prevention of Noise Damage to Cochlear Synapses

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0494 TITLE: Prevention of Noise Damage to Cochlear Synapses PRINCIPAL INVESTIGATOR: Steven Green CONTRACTING...to Cochlear Synapses 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0494 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Steven Green 5d. PROJECT...ABSTRACT Noise-induced synaptopathy is the result of excitotoxic trauma to cochlear synapses due to glutamate released from the hair cells. Excitotoxic

Preventing Ototoxic Synergy of Prior Noise Trauma During Aminoglycoside Therapy

DTIC Science & Technology

2015-12-01

cochlear blood flow . Hearing Research 313, 38-46 (2014). 12. Koo, J.-W. et al. Endotoxemia-mediated inflammation potentiates cochlear uptake of...event in response to a need for higher cochlear blood flow . A 3.7% dilation was adequate for a 20% increase of blood flow 10. On the contrary...summation of the two insults. We have found that prior sound exposure enhances cochlear uptake of aminoglycosides, providing a mechanistic basis for the
Scala vestibuli cochlear implantation in patients with partially ossified cochleas.

PubMed

Berrettini, Stefano; Forli, Francesca; Neri, Emanuele; Segnini, Giovanni; Franceschini, Stefano Sellari

2002-11-01

Partial cochlear obstruction is a relatively common finding in candidates for cochlear implants and frequently involves the inferior segment of the scala tympani in the basal turn of the cochlea. In such patients, the scala vestibuli is often patent and offers an alternative site for implantation. The current report describes two patients with such partial obstruction of the inferior segment of the basal cochlear turn, caused in one case by systemic vasculitis (Takayasu's disease) and in the other by obliterative otosclerosis. A scala vestibuli implantation allowed for complete insertion of the electrode array. No problems were encountered during the surgical procedures and the good post-operative hearing and communicative outcomes achieved were similar to those reported in patients without cochlear ossification. The importance of accurate pre-operative radiological study of the inner ear is underscored, to disclose the presence and define the features of the cochlear ossification and ultimately to properly plan the surgical approach.
Hearing rehabilitation with a binaural cochlear implant in a patient with Erdheim-Chester disease.

PubMed

Querat, Charlotte; Thai-Van, Hung; Durand, Denis Vital; Cotton, François; Gallego, Stéphane; Truy, Eric

2015-09-01

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis. This paper reports an exceptional case of bilateral neural involvement, responsible for profound hearing loss. Bilateral cochlear implantation was performed. We present a 57-year-old man affected by ECD with profound bilateral hearing loss. The patient underwent cochlear implantation with a binaural Digisonic(®) cochlear implant, 7 years after the initial diagnosis. Speech intelligibility rose to a plateau after about 6 months of cochlear implant use. The average outcome of speech intelligibility over time was 55% for dissyllabic words without lip reading, and 70% for sentences. Perception score decreased before the patient died from ECD. A description of the ECD and its otological manifestations is presented. This paper reports the effective hearing rehabilitation of profound bilateral hearing loss by the means of a binaural Digisonic(®) cochlear implant.
Spiral Form of the Human Cochlea Results from Spatial Constraints.

PubMed

Pietsch, M; Aguirre Dávila, L; Erfurt, P; Avci, E; Lenarz, T; Kral, A

2017-08-08

The human inner ear has an intricate spiral shape often compared to shells of mollusks, particularly to the nautilus shell. It has inspired many functional hearing theories. The reasons for this complex geometry remain unresolved. We digitized 138 human cochleae at microscopic resolution and observed an astonishing interindividual variability in the shape. A 3D analytical cochlear model was developed that fits the analyzed data with high precision. The cochlear geometry neither matched a proposed function, namely sound focusing similar to a whispering gallery, nor did it have the form of a nautilus. Instead, the innate cochlear blueprint and its actual ontogenetic variants were determined by spatial constraints and resulted from an efficient packing of the cochlear duct within the petrous bone. The analytical model predicts well the individual 3D cochlear geometry from few clinical measures and represents a clinical tool for an individualized approach to neurosensory restoration with cochlear implants.
Trends in Cochlear Implants

PubMed Central

Zeng, Fan-Gang

2004-01-01

More than 60,000 people worldwide use cochlear implants as a means to restore functional hearing. Although individual performance variability is still high, an average implant user can talk on the phone in a quiet environment. Cochlear-implant research has also matured as a field, as evidenced by the exponential growth in both the patient population and scientific publication. The present report examines current issues related to audiologic, clinical, engineering, anatomic, and physiologic aspects of cochlear implants, focusing on their psychophysical, speech, music, and cognitive performance. This report also forecasts clinical and research trends related to presurgical evaluation, fitting protocols, signal processing, and postsurgical rehabilitation in cochlear implants. Finally, a future landscape in amplification is presented that requires a unique, yet complementary, contribution from hearing aids, middle ear implants, and cochlear implants to achieve a total solution to the entire spectrum of hearing loss treatment and management. PMID:15247993
Ion flow in cochlear hair cells and the regulation of hearing sensitivity.

PubMed

Patuzzi, Robert

2011-10-01

This paper discusses how ion transport proteins in the hair cells of the mammalian cochlea work to produce a sensitive but stable hearing organ. The transport proteins in the inner and outer hair cells are summarized (including their current voltage characteristics), and the roles of these proteins in determining intracellular Ca(2+), membrane potential, and ultimately cochlear sensitivity are discussed. The paper also discusses the role of the Ca(2+) sequestration sacs in outer hair cells in the autoregulation of hair cell membrane potential and cochlear gain, and how the underdamped control of Ca(2+) within these sacs may produce the observed slow oscillations in cochlear sensitivity and otoacoustic emissions after cochlear perturbations, including perilymphatic perfusions and prolonged low-frequency tones. The relative insensitivity of cochlear gain to short-term changes in the endocochlear potential is also discussed. Copyright © 2011 Elsevier B.V. All rights reserved.
The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome.

PubMed

Koyama, Hajime; Kashio, Akinori; Sakata, Aki; Tsutsumiuchi, Katsuhiro; Matsumoto, Yu; Karino, Shotaro; Kakigi, Akinobu; Iwasaki, Shinichi; Yamasoba, Tatsuya

2016-01-01

Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, high-resolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome.
The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome

PubMed Central

Koyama, Hajime; Kashio, Akinori; Sakata, Aki; Tsutsumiuchi, Katsuhiro; Matsumoto, Yu; Karino, Shotaro; Kakigi, Akinobu; Iwasaki, Shinichi; Yamasoba, Tatsuya

2016-01-01

Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, high-resolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome. PMID:27376080
Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area.

PubMed

Cui, Huxing; Sohn, Jong-Woo; Gautron, Laurent; Funahashi, Hisayuki; Williams, Kevin W; Elmquist, Joel K; Lutter, Michael

2012-12-15

The central melanocortin system regulates body energy homeostasis including the melanocortin-4 receptor (MC4R). The lateral hypothalamic area (LHA) receives dense melanocortinergic inputs from the arcuate nucleus of the hypothalamus and regulates multiple processes including food intake, reward behaviors, and autonomic function. By using a mouse line in which green fluorescent protein (GFP) is expressed under control of the MC4R gene promoter, we systemically investigated MC4R signaling in the LHA by combining double immunohistochemistry, electrophysiology, and retrograde tracing techniques. We found that LHA MC4R-GFP neurons coexpress neurotensin as well as the leptin receptor but do not coexpress other peptide neurotransmitters found in the LHA including orexin, melanin-concentrating hormone, and nesfatin-1. Furthermore, electrophysiological recording demonstrated that leptin, but not the MC4R agonist melanotan II, hyperpolarizes the majority of LHA MC4R-GFP neurons in an ATP- sensitive potassium channel-dependent manner. Retrograde tracing revealed that LHA MC4R-GFP neurons do not project to the ventral tegmental area, dorsal raphe nucleus, nucleus accumbens, and spinal cord, and only limited number of neurons project to the nucleus of the solitary tract and parabrachial nucleus. Our findings provide new insights into MC4R signaling in the LHA and its potential implications in homeostatic regulation of body energy balance. Copyright © 2012 Wiley Periodicals, Inc.
Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs.

PubMed

Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D; Pelletier, Jerry; Ferraiuolo, Maria A; Sonenberg, Nahum

2008-07-01

Eukaryotic initiation factor (eIF) 4E, the mRNA 5'-cap-binding protein, mediates the association of eIF4F with the mRNA 5'-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (approximately 30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization.
Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

PubMed Central

Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D.; Pelletier, Jerry; Ferraiuolo, Maria A.; Sonenberg, Nahum

2008-01-01

Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (∼30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras–expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization. PMID:18515545
Effects of central nervous system residua on cochlear implant results in children deafened by meningitis.

PubMed

Francis, Howard W; Pulsifer, Margaret B; Chinnici, Jill; Nutt, Robert; Venick, Holly S; Yeagle, Jennifer D; Niparko, John K

2004-05-01

This study explored factors associated with speech recognition outcomes in postmeningitic deafness (PMD). The results of cochlear implantation may vary in children with PMD because of sequelae that extend beyond the auditory periphery. To determine which factors might be most determinative of outcome of cochlear implantation in children with PMD. Retrospective chart review. A referral center for pediatric cochlear implantation and rehabilitation. Thirty children with cochlear implants who were deafened by meningitis were matched with subjects who were deafened by other causes based on the age at diagnosis, age at cochlear implantation, age at which hearing aids were first used, and method of communication used at home or in the classroom. Speech perception performance within the first 2 years after cochlear implantation and its relationship with presurgical cognitive measures and medical history. There was no difference in the overall cognitive or postoperative speech perception performance between the children with PMD and those deafened by other causes. The presence of postmeningitic hydrocephalus, however, posed greater challenges to the rehabilitation process, as indicated by significantly smaller gains in speech perception and a predilection for behavioral problems. By comparison, cochlear scarring and incomplete electrode insertion had no impact on speech perception results. Although the results demonstrated no significant delay in cognitive or speech perception performance in the PMD group, central nervous system residua, when present, can impede the acquisition of speech perception with a cochlear implant. Central effects associated with PMD may thus impact language learning potential; cognitive and behavioral therapy should be considered in rehabilitative planning and in establishing expectations of outcome.
A Preliminary Investigation of the Air-Bone Gap: Changes in Intracochlear Sound Pressure With Air- and Bone-conducted Stimuli After Cochlear Implantation.

PubMed

Banakis Hartl, Renee M; Mattingly, Jameson K; Greene, Nathaniel T; Jenkins, Herman A; Cass, Stephen P; Tollin, Daniel J

2016-10-01

A cochlear implant electrode within the cochlea contributes to the air-bone gap (ABG) component of postoperative changes in residual hearing after electrode insertion. Preservation of residual hearing after cochlear implantation has gained importance as simultaneous electric-acoustic stimulation allows for improved speech outcomes. Postoperative loss of residual hearing has previously been attributed to sensorineural changes; however, presence of increased postoperative ABG remains unexplained and could result in part from altered cochlear mechanics. Here, we sought to investigate changes to these mechanics via intracochlear pressure measurements before and after electrode implantation to quantify the contribution to postoperative ABG. Human cadaveric heads were implanted with titanium fixtures for bone conduction transducers. Velocities of stapes capitulum and cochlear promontory between the two windows were measured using single-axis laser Doppler vibrometry and fiber-optic sensors measured intracochlear pressures in scala vestibuli and tympani for air- and bone-conducted stimuli before and after cochlear implant electrode insertion through the round window. Intracochlear pressures revealed only slightly reduced responses to air-conducted stimuli consistent with previous literature. No significant changes were noted to bone-conducted stimuli after implantation. Velocities of the stapes capitulum and the cochlear promontory to both stimuli were stable after electrode placement. Presence of a cochlear implant electrode causes alterations in intracochlear sound pressure levels to air, but not bone, conducted stimuli and helps to explain changes in residual hearing noted clinically. These results suggest the possibility of a cochlear conductive component to postoperative changes in hearing sensitivity.
Reprogramming of Somatic Cells Towards Pluripotency by Cell Fusion.

PubMed

Malinowski, Andrzej R; Fisher, Amanda G

2016-01-01

Pluripotent reprogramming can be dominantly induced in a somatic nucleus upon fusion with a pluripotent cell such as embryonic stem (ES) cell. Cell fusion between ES cells and somatic cells results in the formation of heterokaryons, in which the somatic nuclei begin to acquire features of the pluripotent partner. The generation of interspecies heterokaryons between mouse ES- and human somatic cells allows an experimenter to distinguish the nuclear events occurring specifically within the reprogrammed nucleus. Therefore, cell fusion provides a simple and rapid approach to look at the early nuclear events underlying pluripotent reprogramming. Here, we describe a polyethylene glycol (PEG)-mediated cell fusion protocol to generate interspecies heterokaryons and intraspecies hybrids between ES cells and B lymphocytes or fibroblasts.
Expression and distribution of TRPV2 in rat brain.

PubMed

Nedungadi, Thekkethil Prashant; Dutta, Mayurika; Bathina, Chandra Sekhar; Caterina, Michael J; Cunningham, J Thomas

2012-09-01

Transient receptor potential (TRP) proteins are non-selective cation channels that mediate sensory transduction. The neuroanatomical localization and the physiological roles of isoform TRPV2 in the rodent brain are largely unknown. We report here the neuroanatomical distribution of TRPV2 in the adult male rat brain focusing on the hypothalamus and hindbrain regions involved in osmoregulation, autonomic function and energy metabolism. For this we utilized immunohistochemistry combined with brightfield microscopy. In the forebrain, the densest immunostaining was seen in both the supraoptic nucleus (SON) and the magnocellular division of the paraventricular nucleus (PVN) of the hypothalamus. TRPV2 immunoreactivity was also seen in the organum vasculosum of the lamina terminalis, the median preoptic nucleus and the subfornical organ, in addition to the arcuate nucleus of the hypothalamus (ARH), the medial forebrain bundle, the cingulate cortex and the globus pallidus to name a few. In the hindbrain, intense staining was seen in the nucleus of the solitary tract, hypoglossal nucleus, nucleus ambiguous, and the rostral division of the ventrolateral medulla (RVLM) and some mild staining in the area prostrema. To ascertain the specificity of the TRPV2 antibody used in this paper, we compared the TRPV2 immunoreactivity of wildtype (WT) and knockout (KO) mouse brain tissue. Double immunostaining with arginine vasopressin (AVP) using confocal microscopy showed a high degree of colocalization of TRPV2 in the magnocellular SON and PVN. Using laser capture microdissection (LCM) we also show that AVP neurons in the SON contain TRPV2 mRNA. TRPV2 was also co-localized with dopamine beta hydroxylase (DBH) in the NTS and the RVLM of the hindbrain. Based on our results, TRPV2 may play an important role in several CNS networks that regulate body fluid homeostasis, autonomic function, and metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.
Expression and Distribution of TRPV2 in Rat Brain

PubMed Central

Nedungadi, Thekkethil Prashant; Dutta, Mayurika; Bathina, Chandra Sekhar; Caterina, Michael J; Cunningham, J. Thomas

2012-01-01

Transient receptor potential (TRP) proteins are non-selective cation channels that mediate sensory transduction. The neuroanatomical localization and the physiological roles of isoform TRPV2 in the rodent brain are largely unknown. We report here the neuroanatomical distribution of TRPV2 in the adult male rat brain focusing on hypothalamus and hindbrain regions involved in osmoregulation, autonomic function and energy metabolism. For this we utilized immunohistochemistry combined with brighfield microscopy. In the forebrain, the densest immunostaining was seen in both the supraoptic nucleus (SON) and the magnocellular division of the paraventricular nucleus (PVN) of the hypothalamus. TRPV2 immunoreactivity was also seen in the organum vasculosum of the lamina terminalis, the median preoptic nucleus and the subfornical organ, in addition to the arcuate nucleus of the hypothalamus (ARH), the medial forebrain bundle, the cingulate cortex and the globus pallidus to name a few. In the hindbrain, intense staining was seen in the nucleus of the solitary tract, hypoglossal nucleus, nucleus ambiguous, and the rostral division of the ventrolateral medulla (RVLM) and some mild staining in the area prostrema. To ascertain the specificity of the TRPV2 antibody used in this paper, we compared the TRPV2 immunoreactivity of wildtype (WT) and knockout (KO) mouse brain tissue. Double immunostaining with arginine vasopressin (AVP) using confocal microscopy showed a high degree of colocalization of TRPV2 in the magnocellular SON and PVN. Using laser capture microdissection (LCM) we also show that AVP neurons in the SON contain TRPV2 mRNA. TRPV2 was also co-localized with dopamine beta hydroxylase (DBH) in the NTS and the RVLM of the hindbrain. Based on our results, TRPV2 may play an important role in several CNS networks that regulate body fluid homeostasis, autonomic function, and metabolism. PMID:22750329
Cochlear implants in Waardenburg syndrome.

PubMed

Cullen, Robert D; Zdanski, Carlton; Roush, Patricia; Brown, Carolyn; Teagle, Holly; Pillsbury, Harold C; Buchman, Craig

2006-07-01

Waardenburg syndrome is an autosomal-dominant syndrome characterized by dystopia canthorum, hyperplasia of the eyebrows, heterochromia irides, a white forelock, and sensorineural hearing loss in 20% to 55% of patients. This patient population accounts for approximately 2% of congenitally deaf children. The purpose of this retrospective case review was to describe the outcomes for those children with Waardenburg syndrome who have undergone cochlear implantation. Pediatric cochlear implant recipients with documented evidence of Waardenburg syndrome underwent retrospective case review. All patients received their cochlear implants at the study institution followed by outpatient auditory habilitation. Charts were reviewed for etiology and duration of deafness, age at time of cochlear implantation, perioperative complications, duration of use, and performance outcomes. Results of standard tests batteries for speech perception and production administered as a part of the patients' auditory habilitation were reviewed. Seven patients with Waardenburg syndrome and cochlear implants were identified. The average age at implantation was 37 months (range, 18-64 months) and the average duration of use was 69 months (range, 12-143 months). All of these patients are active users of their devices and perform very well after implantation. There were no major complications in this small group of patients. Children with congenital sensorineural hearing loss without other comorbidities (e.g., developmental delay, inner ear malformations) perform well when they receive cochlear implantation and auditory habilitation. Patients with Waardenburg syndrome can be expected to have above-average performance after cochlear implantation.
Surgical Management of the Pediatric Cochlear Implant Patient.

ERIC Educational Resources Information Center

Cohen, Seth M.; Haynes, David S.

2003-01-01

This article discusses the surgical management of children receiving cochlear implants. It identifies preoperative considerations to select patients likely to benefit, contraindications, some new surgical techniques, complications, special considerations (otitis media, meningitis, head growth, inner ear malformations, and cochlear obstruction).…
Histological and reference system for the analysis of mouse intervertebral disc.

PubMed

Tam, Vivian; Chan, Wilson C W; Leung, Victor Y L; Cheah, Kathryn S E; Cheung, Kenneth M C; Sakai, Daisuke; McCann, Matthew R; Bedore, Jake; Séguin, Cheryle A; Chan, Danny

2018-01-01

A new scoring system based on histo-morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially induced IVD degeneration were assessed. Morphological features consistently observed in normal, and early/later stages of degeneration were categorized into a scoring system focused on nucleus pulposus (NP) and annulus fibrosus (AF) changes. "Normal NP" exhibited a highly cellularized cell mass that decreased with natural ageing and in disc degeneration. "Normal AF" consisted of distinct concentric lamellar structures, which was disrupted in severe degeneration. NP/AF clefts indicated more severe changes. Consistent scores were obtained between experienced and new users. Altogether, our scoring system effectively differentiated IVD changes in various strains of wild-type and genetically modified mice and in induced models of IVD degeneration, and is applicable from the post-natal stage to the aged mouse. This scoring tool and reference resource addresses a pressing need in the field for studying IVD changes and cross-study comparisons in mice, and facilitates a means to normalize mouse IVD assessment between different laboratories. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:233-243, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Benefits of Localization and Speech Perception with Multiple Noise Sources in Listeners with a Short-electrode Cochlear Implant

PubMed Central

Dunn, Camille C.; Perreau, Ann; Gantz, Bruce; Tyler, Richard

2009-01-01

Background Research suggests that for individuals with significant low-frequency hearing, implantation of a short-electrode cochlear implant may provide benefits of improved speech perception abilities. Because this strategy combines acoustic and electrical hearing within the same ear while at the same time preserving low-frequency residual acoustic hearing in both ears, localization abilities may also be improved. However, very little research has focused on the localization and spatial hearing abilities of users with a short-electrode cochlear implant. Purpose The purpose of this study was to evaluate localization abilities for listeners with a short-electrode cochlear implant who continue to wear hearing aids in both ears. A secondary purpose was to document speech perception abilities using a speech in noise test with spatially-separate noise sources. Research Design Eleven subjects that utilized a short-electrode cochlear implant and bilateral hearing aids were tested on localization and speech perception with multiple noise locations using an eight-loudspeaker array. Performance was assessed across four listening conditions using various combinations of cochlear implant and/or hearing aid use. Results Results for localization showed no significant difference between using bilateral hearing aids and bilateral hearing aids plus the cochlear implant. However, there was a significant difference between the bilateral hearing aid condition and the implant plus use of a contralateral hearing aid for all eleven subjects. Results for speech perception showed a significant benefit when using bilateral hearing aids plus the cochlear implant over use of the implant plus only one hearing aid. Conclusion Combined use of both hearing aids and the cochlear implant show significant benefits for both localization and speech perception in noise for users with a short-electrode cochlear implant. These results emphasize the importance of low-frequency information in two ears for the purpose of localization and speech perception in noise. PMID:20085199

Benefits of localization and speech perception with multiple noise sources in listeners with a short-electrode cochlear implant.

PubMed

Dunn, Camille C; Perreau, Ann; Gantz, Bruce; Tyler, Richard S

2010-01-01

Research suggests that for individuals with significant low-frequency hearing, implantation of a short-electrode cochlear implant may provide benefits of improved speech perception abilities. Because this strategy combines acoustic and electrical hearing within the same ear while at the same time preserving low-frequency residual acoustic hearing in both ears, localization abilities may also be improved. However, very little research has focused on the localization and spatial hearing abilities of users with a short-electrode cochlear implant. The purpose of this study was to evaluate localization abilities for listeners with a short-electrode cochlear implant who continue to wear hearing aids in both ears. A secondary purpose was to document speech perception abilities using a speech-in-noise test with spatially separate noise sources. Eleven subjects that utilized a short-electrode cochlear implant and bilateral hearing aids were tested on localization and speech perception with multiple noise locations using an eight-loudspeaker array. Performance was assessed across four listening conditions using various combinations of cochlear implant and/or hearing aid use. Results for localization showed no significant difference between using bilateral hearing aids and bilateral hearing aids plus the cochlear implant. However, there was a significant difference between the bilateral hearing aid condition and the implant plus use of a contralateral hearing aid for all 11 subjects. Results for speech perception showed a significant benefit when using bilateral hearing aids plus the cochlear implant over use of the implant plus only one hearing aid. Combined use of both hearing aids and the cochlear implant show significant benefits for both localization and speech perception in noise for users with a short-electrode cochlear implant. These results emphasize the importance of low-frequency information in two ears for the purpose of localization and speech perception in noise.
Acute hyperfibrinogenemia impairs cochlear blood flow and hearing function in guinea pigs in vivo.

PubMed

Ihler, Fritz; Strieth, Sebastian; Pieri, Nicos; Göhring, Peter; Canis, Martin

2012-03-01

Impairment of microcirculation is a possible cause of sudden sensorineural hearing loss (SSNHL). Fibrinogen is known as a risk factor for both microvascular dysfunction and SSNHL. Therefore, the aim of this study was to investigate the effect of elevated serum levels of fibrinogen on cochlear blood flow and hearing function in vivo. One group of guinea pigs received two consecutive injections of 100 mg fibrinogen while a control group received equimolar doses of albumin. Measurements of cochlear microcirculation by intravital microscopy and of hearing thresholds by auditory brainstem response (ABR) recordings were carried out before, after first and after second injection. Ten healthy guinea pigs were randomly assigned to a treatment group or a control group of five animals each. Serum fibrinogen levels were elevated after the first and second injections of fibrinogen compared to basal values and control group respectively. Increasing levels of fibrinogen were paralleled by decreasing cochlear blood flow as well as increasing hearing thresholds. Hearing threshold correlated negatively with cochlear blood flow. The effect of microcirculatory impairment on hearing function could be explained by a malfunction of the cochlear amplifier. Further investigation is needed to quantify cochlear potentials under elevated serum fibrinogen levels.
Meningitis following cochlear implantation: pathomechanisms, clinical symptoms, conservative and surgical treatments.

PubMed

Arnold, W; Bredberg, G; Gstöttner, W; Helms, J; Hildmann, H; Kiratzidis, T; Müller, J; Ramsden, R T; Roland, P; Walterspiel, J N

2002-01-01

Pneumococcal otogenic meningitis is a rare postsurgical complication that can develop following stapedectomy or after cochlear implantation. The bacterial infection can be fatal in some instances. A recent increase in the incidence of otogenic meningitis among cochlear implant wearers is of concern. The majority of meningitis cases are associated with a 2-component electrode manufactured by one cochlear implant company. The device with the added 'positioner' component has been withdrawn from the market (FDA Public Health Web Notification: Cochlear Implant Recipients may be at Greater Risk for Meningitis, Updated: August 29, 2002, www.fda.gov/cdrh/safety/cochlear.html). Not all cases have been subsequent to otitis media and symptoms have developed from less than 24 h up to a few years after implantation. The purpose of this paper is to review and discuss the pathogenesis, pathology/bacteriology and to elaborate on some clinical features of otogenic meningitis in implanted children and adults. Essential aspects of surgery, electrode design, and cochleostomy seal are discussed. Conclusions are drawn from the available data and recommendations are made for good practice in cochlear implantation and follow-up. Copyright 2002 S. Karger AG, Basel
Use of a gentamicin-impregnated collagen sheet (Collatamp(®)) in the management of major soft tissue complications in pediatric cochlear implants.

PubMed

Benito-González, Fernando; Benito, Jose; Sánchez, Luis Alberto Guardado; Estevez Alonso, Santiago; Muñoz Herrera, Angel; Batuecas-Caletrio, Angel

2014-09-01

The objective was to report the effectiveness of salvage treatment in soft tissue infection around cochlear implants with an absorbable gentamicin collagen sheet and a periosteum and skin rotation flaps. Three patients with cochlear implant and persistent surrounding soft tissue infection are included. All of them underwent antibiotic treatment prior to surgery without any response. In this study preoperative and postoperative audiograms were practiced. Surgical excision of infectious skin and a periosteum and skin rotation flaps were performed. The cochlear implant was refixed in the temporal bone and a gentamicin-impregnated collagen sheet was located covering the cochlear implant. headings In all patients with soft tissue infection around the cochlear implant, infection was completely resolved. It was not necessary to remove the device in any case. The use of an absorbable gentamicin-impregnated collagen sheet is not described for the management of soft tissue complications in pediatric cochlear implant patients. The local application of high concentrations of antibiotic administered by this sheet may be effective against resistant bacteria and, in conjunction with surgery, may resolve this type of complications.
Cortical Auditory Evoked Potentials Recorded From Nucleus Hybrid Cochlear Implant Users.

PubMed

Brown, Carolyn J; Jeon, Eun Kyung; Chiou, Li-Kuei; Kirby, Benjamin; Karsten, Sue A; Turner, Christopher W; Abbas, Paul J

2015-01-01

Nucleus Hybrid Cochlear Implant (CI) users hear low-frequency sounds via acoustic stimulation and high-frequency sounds via electrical stimulation. This within-subject study compares three different methods of coordinating programming of the acoustic and electrical components of the Hybrid device. Speech perception and cortical auditory evoked potentials (CAEP) were used to assess differences in outcome. The goals of this study were to determine whether (1) the evoked potential measures could predict which programming strategy resulted in better outcome on the speech perception task or was preferred by the listener, and (2) CAEPs could be used to predict which subjects benefitted most from having access to the electrical signal provided by the Hybrid implant. CAEPs were recorded from 10 Nucleus Hybrid CI users. Study participants were tested using three different experimental processor programs (MAPs) that differed in terms of how much overlap there was between the range of frequencies processed by the acoustic component of the Hybrid device and range of frequencies processed by the electrical component. The study design included allowing participants to acclimatize for a period of up to 4 weeks with each experimental program prior to speech perception and evoked potential testing. Performance using the experimental MAPs was assessed using both a closed-set consonant recognition task and an adaptive test that measured the signal-to-noise ratio that resulted in 50% correct identification of a set of 12 spondees presented in background noise. Long-duration, synthetic vowels were used to record both the cortical P1-N1-P2 "onset" response and the auditory "change" response (also known as the auditory change complex [ACC]). Correlations between the evoked potential measures and performance on the speech perception tasks are reported. Differences in performance using the three programming strategies were not large. Peak-to-peak amplitude of the ACC was not found to be sensitive enough to accurately predict the programming strategy that resulted in the best performance on either measure of speech perception. All 10 Hybrid CI users had residual low-frequency acoustic hearing. For all 10 subjects, allowing them to use both the acoustic and electrical signals provided by the implant improved performance on the consonant recognition task. For most subjects, it also resulted in slightly larger cortical change responses. However, the impact that listening mode had on the cortical change responses was small, and again, the correlation between the evoked potential and speech perception results was not significant. CAEPs can be successfully measured from Hybrid CI users. The responses that are recorded are similar to those recorded from normal-hearing listeners. The goal of this study was to see if CAEPs might play a role either in identifying the experimental program that resulted in best performance on a consonant recognition task or in documenting benefit from the use of the electrical signal provided by the Hybrid CI. At least for the stimuli and specific methods used in this study, no such predictive relationship was found.
Mouse vocal communication system: are ultrasounds learned or innate?

PubMed Central

Arriaga, Gustavo; Jarvis, Erich D.

2013-01-01

Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production. Here we discuss the available data to assess whether male mouse song behavior and the supporting brain circuits resemble those of known vocal non-learning or vocal learning species. Recent neurobiology studies have demonstrated that the mouse USV brain system includes motor cortex and striatal regions, and that the vocal motor cortex sends a direct sparse projection to the brainstem vocal motor nucleus ambiguous, a projection thought be unique to humans among mammals. Recent behavioral studies have reported opposing conclusions on mouse vocal plasticity, including vocal ontogeny changes in USVs over early development that might not be explained by innate maturation processes, evidence for and against a role for auditory feedback in developing and maintaining normal mouse USVs, and evidence for and against limited vocal imitation of song pitch. To reconcile these findings, we suggest that the trait of vocal learning may not be dichotomous but encompass a broad set of behavioral and neural traits we call the continuum hypothesis, and that mice possess some of the traits associated with a capacity for limited vocal learning. PMID:23295209
Localization of PPAR isotypes in the adult mouse and human brain

PubMed Central

Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B.; Mayfield, R. Dayne; Harris, R. Adron

2016-01-01

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain. PMID:27283430
Localization of PPAR isotypes in the adult mouse and human brain.

PubMed

Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B; Mayfield, R Dayne; Harris, R Adron

2016-06-10

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain.
The GABA[subscript A] Receptor Agonist Muscimol Induces an Age- and Region-Dependent Form of Long-Term Depression in the Mouse Striatum

ERIC Educational Resources Information Center

Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

2016-01-01

Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABA[subscript A] receptor agonist muscimol was recently found to trigger a…
Cochlear Implantation after Bilateral Transverse Temporal Bone Fractures

PubMed Central

Shin, Jong-Heon; Park, SooChan; Baek, Sam-Hyun

2008-01-01

Patients deafened by a severe head injury are rarely encountered. We report a case of a 65-yr-old man with bilateral transverse temporal bone fractures due to head injury. He underwent cochlear implant and achieved a satisfactory auditory rehabilitation. Imaging studies of temporal bone before performing a cochlear implantation provide important information on a patient with bilateral temporal bone fractures. Cochlear implantations with careful planning in such a patient may be a very effective method for aural rehabilitation. PMID:19434252
The contribution of short-term memory capacity to reading ability in adolescents with cochlear implants.

PubMed

Edwards, Lindsey; Aitkenhead, Lynne; Langdon, Dawn

2016-11-01

This study aimed to establish the relationship between short-term memory capacity and reading skills in adolescents with cochlear implants. A between-groups design compared a group of young people with cochlear implants with a group of hearing peers on measures of reading, and auditory and visual short-term memory capacity. The groups were matched for non-verbal IQ and age. The adolescents with cochlear implants were recruited from the Cochlear Implant Programme at a specialist children's hospital. The hearing participants were recruited from the same schools as those attended by the implanted adolescents. Participants were 18 cochlear implant users and 14 hearing controls, aged between 12 and 18 years. All used English as their main language and had no significant learning disability or neuro-developmental disorder. Short-term memory capacity was assessed in the auditory modality using Forward and Reverse Digit Span from the WISC IV UK, and visually using Forward and Reverse Memory from the Leiter-R. Individual word reading, reading comprehension and pseudoword decoding were assessed using the WIAT II UK. A series of ANOVAs revealed that the adolescents with cochlear implants had significantly poorer auditory short-term memory capacity and reading skills (on all measures) compared with their hearing peers. However, when Forward Digit Span was entered into the analyses as a covariate, none of the differences remained statistically significant. Deficits in immediate auditory memory persist into adolescence in deaf children with cochlear implants. Short-term auditory memory capacity is an important neurocognitive process in the development of reading skills after cochlear implantation in childhood that remains evident in later adolescence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
A preliminary investigation of the air-bone gap: Changes in intracochlear sound pressure with air- and bone-conducted stimuli after cochlear implantation

PubMed Central

Banakis Hartl, Renee M.; Mattingly, Jameson K.; Greene, Nathaniel T.; Jenkins, Herman A.; Cass, Stephen P.; Tollin, Daniel J.

2016-01-01

Hypothesis A cochlear implant electrode within the cochlea contributes to the air-bone gap (ABG) component of postoperative changes in residual hearing after electrode insertion. Background Preservation of residual hearing after cochlear implantation has gained importance as simultaneous electric-acoustic stimulation allows for improved speech outcomes. Postoperative loss of residual hearing has previously been attributed to sensorineural changes; however, presence of increased postoperative air-bone gap remains unexplained and could result in part from altered cochlear mechanics. Here, we sought to investigate changes to these mechanics via intracochlear pressure measurements before and after electrode implantation to quantify the contribution to postoperative air-bone gap. Methods Human cadaveric heads were implanted with titanium fixtures for bone conduction transducers. Velocities of stapes capitulum and cochlear promontory between the two windows were measured using single-axis laser Doppler vibrometry and fiber-optic sensors measured intracochlear pressures in scala vestibuli and tympani for air- and bone-conducted stimuli before and after cochlear implant electrode insertion through the round window. Results Intracochlear pressures revealed only slightly reduced responses to air-conducted stimuli consistent with prior literature. No significant changes were noted to bone-conducted stimuli after implantation. Velocities of the stapes capitulum and the cochlear promontory to both stimuli were stable following electrode placement. Conclusion Presence of a cochlear implant electrode causes alterations in intracochlear sound pressure levels to air, but not bone, conducted stimuli and helps to explain changes in residual hearing noted clinically. These results suggest the possibility of a cochlear conductive component to postoperative changes in hearing sensitivity. PMID:27579835
ROS are critical for endometrial breakdown via NF-κB-COX-2 signaling in a female mouse menstrual-like model.

PubMed

Wu, Bin; Chen, Xihua; He, Bin; Liu, Shuyan; Li, Yunfeng; Wang, Qianxing; Gao, Haijun; Wang, Shufang; Liu, Jianbing; Zhang, Shucheng; Xu, Xiangbo; Wang, Jiedong

2014-09-01

Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.
Anatomical and Molecular Properties of Long Descending Propriospinal Neurons in Mice

PubMed Central

Flynn, Jamie R.; Conn, Victoria L.; Boyle, Kieran A.; Hughes, David I.; Watanabe, Masahiko; Velasquez, Tomoko; Goulding, Martyn D.; Callister, Robert J.; Graham, Brett A.

2017-01-01

Long descending propriospinal neurons (LDPNs) are interneurons that form direct connections between cervical and lumbar spinal circuits. LDPNs are involved in interlimb coordination and are important mediators of functional recovery after spinal cord injury (SCI). Much of what we know about LDPNs comes from a range of species, however, the increased use of transgenic mouse lines to better define neuronal populations calls for a more complete characterisation of LDPNs in mice. In this study, we examined the cell body location, inhibitory neurotransmitter phenotype, developmental provenance, morphology and synaptic inputs of mouse LDPNs throughout the cervical and upper thoracic spinal cord. LDPNs were retrogradely labelled from the lumbar spinal cord to map cell body locations throughout the cervical and upper thoracic segments. Ipsilateral LDPNs were distributed throughout the dorsal, intermediate and ventral grey matter as well as the lateral spinal nucleus and lateral cervical nucleus. In contrast, contralateral LDPNs were more densely concentrated in the ventromedial grey matter. Retrograde labelling in GlyT2GFP and GAD67GFP mice showed the majority of inhibitory LDPNs project either ipsilaterally or adjacent to the midline. Additionally, we used several transgenic mouse lines to define the developmental provenance of LDPNs and found that V2b positive neurons form a subset of ipsilaterally projecting LDPNs. Finally, a population of Neurobiotin (NB) labelled LDPNs were assessed in detail to examine morphology and plot the spatial distribution of contacts from a variety of neurochemically distinct axon terminals. These results provide important baseline data in mice for future work on their role in locomotion and recovery from SCI. PMID:28220062
Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.

PubMed

Alagramam, K N; Yuan, H; Kuehn, M H; Murcia, C L; Wayne, S; Srisailpathy, C R; Lowry, R B; Knaus, R; Van Laer, L; Bernier, F P; Schwartz, S; Lee, C; Morton, C C; Mullins, R F; Ramesh, A; Van Camp, G; Hageman, G S; Woychik, R P; Smith, R J; Hagemen, G S

2001-08-01

We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.
Relationships among Professionals' Knowledge, Experience, and Expectations Regarding Cochlear Implants

ERIC Educational Resources Information Center

Ben-Itzhak, D.; Most, T.; Weisel, A.

2005-01-01

The present study examined the relationships between teachers' and communication clinicians' self-reported knowledge on cochlear implants and their expectations of CIs. The authors also explored these professionals' views regarding the child's communication mode, educational setting, and social options following cochlear implantation. The…
The Relationship between Cochlear Implants and Deaf Identity

ERIC Educational Resources Information Center

Chapman, Madeline; Dammeyer, Jesper

2017-01-01

The degree to which individuals with cochlear implants (CIs) experience communication difficulties has implications for social participation and identity development. However, few studies have examined the relationship between cochlear implantation, identity, and social participation. Using data from a Danish national survey of deaf adults, the…
Modulation of Mcl-1 expression reduces age-related cochlear degeneration

PubMed Central

Yang, Wei Ping; Xu, Yang; Guo, Wei Wei; Liu, Hui Zhan; Hu, Bo Hua

2013-01-01

Mcl-1 is an anti-apoptotic member of the Bcl-2 family that modulates apoptosis-related signaling pathways and promotes cell survival. We have previously demonstrated a reduction of Mcl-1 expression in aging cochleae. To investigate whether restoring Mcl-1 expression would reduce aging-related cochlear degeneration, we developed a rat model of Mcl-1 overexpression. A plasmid encoding human Mcl-1/enhanced green fluorescent protein was applied to the round window of the cochlea. This in vivo treatment transfected both the sensory and supporting cells of the cochlear sensory epithelium and enhanced Mcl-1 expression at both the mRNA and the protein level. The upregulation of Mcl-1 expression reduced the progression of age-related cochlear dysfunction and sensory cell death. Furthermore, the transfection of Mcl-1 exerted its protective effect by suppressing cochlear apoptosis at the mitochondrial level. This study demonstrates that the genetic modulation of Mcl-1 expression reduces the progression of age-related cochlear degeneration. PMID:23790646
Evidence of across-channel processing for spectral-ripple discrimination in cochlear implant listeners.

PubMed

Won, Jong Ho; Jones, Gary L; Drennan, Ward R; Jameyson, Elyse M; Rubinstein, Jay T

2011-10-01

Spectral-ripple discrimination has been used widely for psychoacoustical studies in normal-hearing, hearing-impaired, and cochlear implant listeners. The present study investigated the perceptual mechanism for spectral-ripple discrimination in cochlear implant listeners. The main goal of this study was to determine whether cochlear implant listeners use a local intensity cue or global spectral shape for spectral-ripple discrimination. The effect of electrode separation on spectral-ripple discrimination was also evaluated. Results showed that it is highly unlikely that cochlear implant listeners depend on a local intensity cue for spectral-ripple discrimination. A phenomenological model of spectral-ripple discrimination, as an "ideal observer," showed that a perceptual mechanism based on discrimination of a single intensity difference cannot account for performance of cochlear implant listeners. Spectral modulation depth and electrode separation were found to significantly affect spectral-ripple discrimination. The evidence supports the hypothesis that spectral-ripple discrimination involves integrating information from multiple channels. © 2011 Acoustical Society of America
Evidence of across-channel processing for spectral-ripple discrimination in cochlear implant listeners a

PubMed Central

Ho Won, Jong; Jones, Gary L.; Drennan, Ward R.; Jameyson, Elyse M.; Rubinstein, Jay T.

2011-01-01

Spectral-ripple discrimination has been used widely for psychoacoustical studies in normal-hearing, hearing-impaired, and cochlear implant listeners. The present study investigated the perceptual mechanism for spectral-ripple discrimination in cochlear implant listeners. The main goal of this study was to determine whether cochlear implant listeners use a local intensity cue or global spectral shape for spectral-ripple discrimination. The effect of electrode separation on spectral-ripple discrimination was also evaluated. Results showed that it is highly unlikely that cochlear implant listeners depend on a local intensity cue for spectral-ripple discrimination. A phenomenological model of spectral-ripple discrimination, as an “ideal observer,” showed that a perceptual mechanism based on discrimination of a single intensity difference cannot account for performance of cochlear implant listeners. Spectral modulation depth and electrode separation were found to significantly affect spectral-ripple discrimination. The evidence supports the hypothesis that spectral-ripple discrimination involves integrating information from multiple channels. PMID:21973363

Some links on this page may take you to non-federal websites. Their policies may differ from this site.