Endogenous opioid peptide-mediated neurotransmission in central and pericentral nuclei of the inferior colliculus recruits μ1-opioid receptor to modulate post-ictal antinociception.

PubMed

Felippotti, Tatiana Tocchini; de Freitas, Renato Leonardo; Coimbra, Norberto Cysne

2012-02-01

The aim of the present work was to investigate the involvement of the μ1-endogenous opioid peptide receptor-mediated system in post-ictal antinociception. Antinociceptive responses were determined by the tail-flick test after pre-treatment with the selective μ1-opioid receptor antagonist naloxonazine, peripherally or centrally administered at different doses. Peripheral subchronic (24 h) pre-treatment with naloxonazine antagonised the antinociception elicited by tonic-clonic seizures. Acute (10 min) pre-treatment, however, did not have the same effect. In addition, microinjections of naloxonazine into the central, dorsal cortical and external cortical nuclei of the inferior colliculus antagonised tonic-clonic seizure-induced antinociception. Neither acute (10-min) peripheral pre-treatment with naloxonazine nor subchronic intramesencephalic blockade of μ1-opioid receptors resulted in consistent statistically significant differences in the severity of tonic-clonic seizures shown by Racine's index (1972), although the intracollicular specific antagonism of μ1-opioid receptor decreased the duration of seizures. μ1-Opioid receptors and the inferior colliculus have been implicated in several endogenous opioid peptide-mediated responses such as antinociception and convulsion. The present findings suggest the involvement of μ1-opiate receptors of central and pericentral nuclei of the inferior colliculus in the modulation of tonic-clonic seizures and in the organisation of post-ictal antinociception. Copyright © 2011 Elsevier Ltd. All rights reserved.

Deactivation of the inferior colliculus by cooling demonstrates intercollicular modulation of neuronal activity

PubMed Central

Orton, Llwyd D.; Poon, Paul W. F.; Rees, Adrian

2012-01-01

The auditory pathways coursing through the brainstem are organized bilaterally in mirror image about the midline and at several levels the two sides are interconnected. One of the most prominent points of interconnection is the commissure of the inferior colliculus (CoIC). Anatomical studies have revealed that these fibers make reciprocal connections which follow the tonotopic organization of the inferior colliculus (IC), and that the commissure contains both excitatory and, albeit fewer, inhibitory fibers. The role of these connections in sound processing is largely unknown. Here we describe a method to address this question in the anaesthetized guinea pig. We used a cryoloop placed on one IC to produce reversible deactivation while recording electrophysiological responses to sounds in both ICs. We recorded single units, multi-unit clusters and local field potentials (LFPs) before, during and after cooling. The degree and spread of cooling was measured with a thermocouple placed in the IC and other auditory structures. Cooling sufficient to eliminate firing was restricted to the IC contacted by the cryoloop. The temperature of other auditory brainstem structures, including the contralateral IC and the cochlea were minimally affected. Cooling below 20°C reduced or eliminated the firing of action potentials in frequency laminae at depths corresponding to characteristic frequencies up to ~8 kHz. Modulation of neural activity also occurred in the un-cooled IC with changes in single unit firing and LFPs. Components of LFPs signaling lemniscal afferent input to the IC showed little change in amplitude or latency with cooling, whereas the later components, which likely reflect inter- and intra-collicular processing, showed marked changes in form and amplitude. We conclude that the cryoloop is an effective method of selectively deactivating one IC in guinea pig, and demonstrate that auditory processing in the IC is strongly influenced by the other. PMID:23248587

Spike-frequency adaptation in the inferior colliculus.

PubMed

Ingham, Neil J; McAlpine, David

2004-02-01

We investigated spike-frequency adaptation of neurons sensitive to interaural phase disparities (IPDs) in the inferior colliculus (IC) of urethane-anesthetized guinea pigs using a stimulus paradigm designed to exclude the influence of adaptation below the level of binaural integration. The IPD-step stimulus consists of a binaural 3,000-ms tone, in which the first 1,000 ms is held at a neuron's least favorable ("worst") IPD, adapting out monaural components, before being stepped rapidly to a neuron's most favorable ("best") IPD for 300 ms. After some variable interval (1-1,000 ms), IPD is again stepped to the best IPD for 300 ms, before being returned to a neuron's worst IPD for the remainder of the stimulus. Exponential decay functions fitted to the response to best-IPD steps revealed an average adaptation time constant of 52.9 +/- 26.4 ms. Recovery from adaptation to best IPD steps showed an average time constant of 225.5 +/- 210.2 ms. Recovery time constants were not correlated with adaptation time constants. During the recovery period, adaptation to a 2nd best-IPD step followed similar kinetics to adaptation during the 1st best-IPD step. The mean adaptation time constant at stimulus onset (at worst IPD) was 34.8 +/- 19.7 ms, similar to the 38.4 +/- 22.1 ms recorded to contralateral stimulation alone. Individual time constants after stimulus onset were correlated with each other but not with time constants during the best-IPD step. We conclude that such binaurally derived measures of adaptation reflect processes that occur above the level of exclusively monaural pathways, and subsequent to the site of primary binaural interaction.

Responses to amplitude modulated infrared stimuli in the guinea pig inferior colliculus

NASA Astrophysics Data System (ADS)

Richter, Claus-Peter; Young, Hunter

2013-03-01

Responses of units in the central nucleus of the inferior colliculus of the guinea pig were recorded with tungsten electrodes. The set of data presented here is limited to high stimulus levels. The effect of changing the modulation frequency and the modulation depth was explored for acoustic and laser stimuli. The selected units responded to sinusoidal amplitude modulated (AM) tones, AM trains of clicks, and AM trains of laser pulses with a modulation of their spike discharge. At modulation frequencies of 20 Hz, some units tended to respond with 40 Hz to the acoustic stimuli, but only at 20 Hz for the trains of laser pulses. For all modes of stimulation the responses revealed a dominant response to the first cycle of the modulation, with decreasing number of action potential during successive cycles. While amplitude modulated tone bursts and amplitude modulated trains of acoustic clicks showed similar patterns, the response to trains of laser pulses was different.

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

A novel relay nucleus between the inferior colliculus and the optic tectum in the chicken (Gallus gallus).

PubMed

Niederleitner, Bertram; Gutierrez-Ibanez, Cristian; Krabichler, Quirin; Weigel, Stefan; Luksch, Harald

2017-02-15

Processing multimodal sensory information is vital for behaving animals in many contexts. The barn owl, an auditory specialist, is a classic model for studying multisensory integration. In the barn owl, spatial auditory information is conveyed to the optic tectum (TeO) by a direct projection from the external nucleus of the inferior colliculus (ICX). In contrast, evidence of an integration of visual and auditory information in auditory generalist avian species is completely lacking. In particular, it is not known whether in auditory generalist species the ICX projects to the TeO at all. Here we use various retrograde and anterograde tracing techniques both in vivo and in vitro, intracellular fillings of neurons in vitro, and whole-cell patch recordings to characterize the connectivity between ICX and TeO in the chicken. We found that there is a direct projection from ICX to the TeO in the chicken, although this is small and only to the deeper layers (layers 13-15) of the TeO. However, we found a relay area interposed among the IC, the TeO, and the isthmic complex that receives strong synaptic input from the ICX and projects broadly upon the intermediate and deep layers of the TeO. This area is an external portion of the formatio reticularis lateralis (FRLx). In addition to the projection to the TeO, cells in FRLx send, via collaterals, descending projections through tectopontine-tectoreticular pathways. This newly described connection from the inferior colliculus to the TeO provides a solid basis for visual-auditory integration in an auditory generalist bird. J. Comp. Neurol. 525:513-534, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Human inferior colliculus activity relates to individual differences in spoken language learning

PubMed Central

Chandrasekaran, Bharath; Kraus, Nina

2012-01-01

A challenge to learning words of a foreign language is encoding nonnative phonemes, a process typically attributed to cortical circuitry. Using multimodal imaging methods [functional magnetic resonance imaging-adaptation (fMRI-A) and auditory brain stem responses (ABR)], we examined the extent to which pretraining pitch encoding in the inferior colliculus (IC), a primary midbrain structure, related to individual variability in learning to successfully use nonnative pitch patterns to distinguish words in American English-speaking adults. fMRI-A indexed the efficiency of pitch representation localized to the IC, whereas ABR quantified midbrain pitch-related activity with millisecond precision. In line with neural “sharpening” models, we found that efficient IC pitch pattern representation (indexed by fMRI) related to superior neural representation of pitch patterns (indexed by ABR), and consequently more successful word learning following sound-to-meaning training. Our results establish a critical role for the IC in speech-sound representation, consistent with the established role for the IC in the representation of communication signals in other animal models. PMID:22131377

Impaired auditory temporal selectivity in the inferior colliculus of aged Mongolian gerbils.

PubMed

Khouri, Leila; Lesica, Nicholas A; Grothe, Benedikt

2011-07-06

Aged humans show severe difficulties in temporal auditory processing tasks (e.g., speech recognition in noise, low-frequency sound localization, gap detection). A degradation of auditory function with age is also evident in experimental animals. To investigate age-related changes in temporal processing, we compared extracellular responses to temporally variable pulse trains and human speech in the inferior colliculus of young adult (3 month) and aged (3 years) Mongolian gerbils. We observed a significant decrease of selectivity to the pulse trains in neuronal responses from aged animals. This decrease in selectivity led, on the population level, to an increase in signal correlations and therefore a decrease in heterogeneity of temporal receptive fields and a decreased efficiency in encoding of speech signals. A decrease in selectivity to temporal modulations is consistent with a downregulation of the inhibitory transmitter system in aged animals. These alterations in temporal processing could underlie declines in the aging auditory system, which are unrelated to peripheral hearing loss. These declines cannot be compensated by traditional hearing aids (that rely on amplification of sound) but may rather require pharmacological treatment.

Human inferior colliculus activity relates to individual differences in spoken language learning.

PubMed

Chandrasekaran, Bharath; Kraus, Nina; Wong, Patrick C M

2012-03-01

A challenge to learning words of a foreign language is encoding nonnative phonemes, a process typically attributed to cortical circuitry. Using multimodal imaging methods [functional magnetic resonance imaging-adaptation (fMRI-A) and auditory brain stem responses (ABR)], we examined the extent to which pretraining pitch encoding in the inferior colliculus (IC), a primary midbrain structure, related to individual variability in learning to successfully use nonnative pitch patterns to distinguish words in American English-speaking adults. fMRI-A indexed the efficiency of pitch representation localized to the IC, whereas ABR quantified midbrain pitch-related activity with millisecond precision. In line with neural "sharpening" models, we found that efficient IC pitch pattern representation (indexed by fMRI) related to superior neural representation of pitch patterns (indexed by ABR), and consequently more successful word learning following sound-to-meaning training. Our results establish a critical role for the IC in speech-sound representation, consistent with the established role for the IC in the representation of communication signals in other animal models.

The inferior colliculus encodes the Franssen auditory spatial illusion

PubMed Central

Rajala, Abigail Z.; Yan, Yonghe; Dent, Micheal L.; Populin, Luis C.

2014-01-01

Illusions are effective tools for the study of the neural mechanisms underlying perception because neural responses can be correlated to the physical properties of stimuli and the subject’s perceptions. The Franssen illusion (FI) is an auditory spatial illusion evoked by presenting a transient, abrupt tone and a slowly rising, sustained tone of the same frequency simultaneously on opposite sides of the subject. Perception of the FI consists of hearing a single sound, the sustained tone, on the side that the transient was presented. Both subcortical and cortical mechanisms for the FI have been proposed, but, to date, there is no direct evidence for either. The data show that humans and rhesus monkeys perceive the FI similarly. Recordings were taken from single units of the inferior colliculus in the monkey while they indicated the perceived location of sound sources with their gaze. The results show that the transient component of the Franssen stimulus, with a shorter first spike latency and higher discharge rate than the sustained tone, encodes the perception of sound location. Furthermore, the persistent erroneous perception of the sustained stimulus location is due to continued excitation of the same neurons, first activated by the transient, by the sustained stimulus without location information. These results demonstrate for the first time, on a trial-by-trial basis, a correlation between perception of an auditory spatial illusion and a subcortical physiological substrate. PMID:23899307

Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus.

PubMed

Xiong, Xiaorui R; Liang, Feixue; Zingg, Brian; Ji, Xu-ying; Ibrahim, Leena A; Tao, Huizhong W; Zhang, Li I

2015-06-11

Defense against environmental threats is essential for animal survival. However, the neural circuits responsible for transforming unconditioned sensory stimuli and generating defensive behaviours remain largely unclear. Here, we show that corticofugal neurons in the auditory cortex (ACx) targeting the inferior colliculus (IC) mediate an innate, sound-induced flight behaviour. Optogenetic activation of these neurons, or their projection terminals in the IC, is sufficient for initiating flight responses, while the inhibition of these projections reduces sound-induced flight responses. Corticocollicular axons monosynaptically innervate neurons in the cortex of the IC (ICx), and optogenetic activation of the projections from the ICx to the dorsal periaqueductal gray is sufficient for provoking flight behaviours. Our results suggest that ACx can both amplify innate acoustic-motor responses and directly drive flight behaviours in the absence of sound input through corticocollicular projections to ICx. Such corticofugal control may be a general feature of innate defense circuits across sensory modalities.

Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus

PubMed Central

Xiong, Xiaorui R.; Liang, Feixue; Zingg, Brian; Ji, Xu-ying; Ibrahim, Leena A.; Tao, Huizhong W.; Zhang, Li I.

2015-01-01

Defense against environmental threats is essential for animal survival. However, the neural circuits responsible for transforming unconditioned sensory stimuli and generating defensive behaviours remain largely unclear. Here, we show that corticofugal neurons in the auditory cortex (ACx) targeting the inferior colliculus (IC) mediate an innate, sound-induced flight behaviour. Optogenetic activation of these neurons, or their projection terminals in the IC, is sufficient for initiating flight responses, while the inhibition of these projections reduces sound-induced flight responses. Corticocollicular axons monosynaptically innervate neurons in the cortex of the IC (ICx), and optogenetic activation of the projections from the ICx to the dorsal periaqueductal gray is sufficient for provoking flight behaviours. Our results suggest that ACx can both amplify innate acoustic-motor responses and directly drive flight behaviours in the absence of sound input through corticocollicular projections to ICx. Such corticofugal control may be a general feature of innate defense circuits across sensory modalities. PMID:26068082

Stimulus-specific adaptation and deviance detection in the inferior colliculus

PubMed Central

Ayala, Yaneri A.; Malmierca, Manuel S.

2013-01-01

Deviancy detection in the continuous flow of sensory information into the central nervous system is of vital importance for animals. The task requires neuronal mechanisms that allow for an efficient representation of the environment by removing statistically redundant signals. Recently, the neuronal principles of auditory deviance detection have been approached by studying the phenomenon of stimulus-specific adaptation (SSA). SSA is a reduction in the responsiveness of a neuron to a common or repetitive sound while the neuron remains highly sensitive to rare sounds (Ulanovsky et al., 2003). This phenomenon could enhance the saliency of unexpected, deviant stimuli against a background of repetitive signals. SSA shares many similarities with the evoked potential known as the “mismatch negativity,” (MMN) and it has been linked to cognitive process such as auditory memory and scene analysis (Winkler et al., 2009) as well as to behavioral habituation (Netser et al., 2011). Neurons exhibiting SSA can be found at several levels of the auditory pathway, from the inferior colliculus (IC) up to the auditory cortex (AC). In this review, we offer an account of the state-of-the art of SSA studies in the IC with the aim of contributing to the growing interest in the single-neuron electrophysiology of auditory deviance detection. The dependence of neuronal SSA on various stimulus features, e.g., probability of the deviant stimulus and repetition rate, and the roles of the AC and inhibition in shaping SSA at the level of the IC are addressed. PMID:23335883

Passive stimulation and behavioral training differentially transform temporal processing in the inferior colliculus and primary auditory cortex

PubMed Central

Beitel, Ralph E.; Schreiner, Christoph E.; Leake, Patricia A.

2016-01-01

In profoundly deaf cats, behavioral training with intracochlear electric stimulation (ICES) can improve temporal processing in the primary auditory cortex (AI). To investigate whether similar effects are manifest in the auditory midbrain, ICES was initiated in neonatally deafened cats either during development after short durations of deafness (8 wk of age) or in adulthood after long durations of deafness (≥3.5 yr). All of these animals received behaviorally meaningless, “passive” ICES. Some animals also received behavioral training with ICES. Two long-deaf cats received no ICES prior to acute electrophysiological recording. After several months of passive ICES and behavioral training, animals were anesthetized, and neuronal responses to pulse trains of increasing rates were recorded in the central (ICC) and external (ICX) nuclei of the inferior colliculus. Neuronal temporal response patterns (repetition rate coding, minimum latencies, response precision) were compared with results from recordings made in the AI of the same animals (Beitel RE, Vollmer M, Raggio MW, Schreiner CE. J Neurophysiol 106: 944–959, 2011; Vollmer M, Beitel RE. J Neurophysiol 106: 2423–2436, 2011). Passive ICES in long-deaf cats remediated severely degraded temporal processing in the ICC and had no effects in the ICX. In contrast to observations in the AI, behaviorally relevant ICES had no effects on temporal processing in the ICC or ICX, with the single exception of shorter latencies in the ICC in short-deaf cats. The results suggest that independent of deafness duration passive stimulation and behavioral training differentially transform temporal processing in auditory midbrain and cortex, and primary auditory cortex emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf cat. NEW & NOTEWORTHY Behaviorally relevant vs. passive electric stimulation of the auditory nerve differentially affects neuronal temporal processing in the central nucleus of

Changes in the Response Properties of Inferior Colliculus Neurons Relating to Tinnitus

PubMed Central

Berger, Joel I.; Coomber, Ben; Wells, Tobias T.; Wallace, Mark N.; Palmer, Alan R.

2014-01-01

Tinnitus is often identified in animal models by using the gap prepulse inhibition of acoustic startle. Impaired gap detection following acoustic over-exposure (AOE) is thought to be caused by tinnitus “filling in” the gap, thus, reducing its salience. This presumably involves altered perception, and could conceivably be caused by changes at the level of the neocortex, i.e., cortical reorganization. Alternatively, reduced gap detection ability might reflect poorer temporal processing in the brainstem, caused by AOE; in which case, impaired gap detection would not be a reliable indicator of tinnitus. We tested the latter hypothesis by examining gap detection in inferior colliculus (IC) neurons following AOE. Seven of nine unilaterally noise-exposed guinea pigs exhibited behavioral evidence of tinnitus. In these tinnitus animals, neural gap detection thresholds (GDTs) in the IC significantly increased in response to broadband noise stimuli, but not to pure tones or narrow-band noise. In addition, when IC neurons were sub-divided according to temporal response profile (onset vs. sustained firing patterns), we found a significant increase in the proportion of onset-type responses after AOE. Importantly, however, GDTs were still considerably shorter than gap durations commonly used in objective behavioral tests for tinnitus. These data indicate that the neural changes observed in the IC are insufficient to explain deficits in behavioral gap detection that are commonly attributed to tinnitus. The subtle changes in IC neuron response profiles following AOE warrant further investigation. PMID:25346722

Taurine activates strychnine-sensitive glycine receptors in neurons of the rat inferior colliculus.

PubMed

Xu, Han; Zhou, Ke-Qing; Huang, Yi-Na; Chen, Lin; Xu, Tian-Le

2004-09-24

Taurine (Tau) is one of the most abundant free amino acids in the mammalian central nervous system. Whether the neurotransmission of the central auditory system is regulated or modulated by Tau is not clear. In the present study, we investigated the electrophysiological and pharmacological properties of Tau-activated currents in acutely dissociated neurons of the rat inferior colliculus (IC) using whole cell patch clamp recordings. At a holding potential of -60 mV and under a condition of chloride equilibrium potential near 0 mV, Tau activated an inward current and its half-maximal activation concentration was equal to 0.37 mM. The measured reversal potential of Tau-activated currents was close to theoretical chloride equilibrium potential. The currents evoked by Tau at both low (1 mM) and high (10 mM) concentrations were almost completely inhibited by strychnine, a glycine receptor antagonist. The Tau-activated current, however, was not affected by bicuculline, a GABA(A) receptor antagonist. Tau at increased concentrations progressively reduced the current response to subsequent glycine application. At saturated concentrations, Tau-activated current and glycine-activated current were mutually cross-desensitized by each other. These findings indicate that Tau activates glycine receptors in neurons of the rat IC and thus may have a functional role in regulating or modulating the neurotransmission of the central auditory system in mammals.

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.

Is GABA neurotransmission enhanced in auditory thalamus relative to inferior colliculus?

PubMed Central

Cai, Rui; Kalappa, Bopanna I.; Brozoski, Thomas J.; Ling, Lynne L.

2013-01-01

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central auditory system. Sensory thalamic structures show high levels of non-desensitizing extrasynaptic GABAA receptors (GABAARs) and a reduction in the redundancy of coded information. The present study compared the inhibitory potency of GABA acting at GABAARs between the inferior colliculus (IC) and the medial geniculate body (MGB) using quantitative in vivo, in vitro, and ex vivo experimental approaches. In vivo single unit studies compared the ability of half maximal inhibitory concentrations of GABA to inhibit sound-evoked temporal responses, and found that GABA was two to three times (P < 0.01) more potent at suppressing MGB single unit responses than IC unit responses. In vitro whole cell patch-clamp slice recordings were used to demonstrate that gaboxadol, a δ-subunit selective GABAAR agonist, was significantly more potent at evoking tonic inhibitory currents from MGB neurons than IC neurons (P < 0.01). These electrophysiological findings were supported by an in vitro receptor binding assay which used the picrotoxin analog [3H]TBOB to assess binding in the GABAAR chloride channel. MGB GABAARs had significantly greater total open chloride channel capacity relative to GABAARs in IC (P < 0.05) as shown by increased total [3H]TBOB binding. Finally, a comparative ex vivo measurement compared endogenous GABA levels and suggested a trend towards higher GABA concentrations in MGB than in IC. Collectively, these studies suggest that, per unit GABA, high affinity extrasynaptic and synaptic GABAARs confer a significant inhibitory GABAAR advantage to MGB neurons relative to IC neurons. This increased GABA sensitivity likely underpins the vital filtering role of auditory thalamus. PMID:24155003

Noise reduction of coincidence detector output by the inferior colliculus of the barn owl.

PubMed

Christianson, G Björn; Peña, José Luis

2006-05-31

A recurring theme in theoretical work is that integration over populations of similarly tuned neurons can reduce neural noise. However, there are relatively few demonstrations of an explicit noise reduction mechanism in a neural network. Here we demonstrate that the brainstem of the barn owl includes a stage of processing apparently devoted to increasing the signal-to-noise ratio in the encoding of the interaural time difference (ITD), one of two primary binaural cues used to compute the position of a sound source in space. In the barn owl, the ITD is processed in a dedicated neural pathway that terminates at the core of the inferior colliculus (ICcc). The actual locus of the computation of the ITD is before ICcc in the nucleus laminaris (NL), and ICcc receives no inputs carrying information that did not originate in NL. Unlike in NL, the rate-ITD functions of ICcc neurons require as little as a single stimulus presentation per ITD to show coherent ITD tuning. ICcc neurons also displayed a greater dynamic range with a maximal difference in ITD response rates approximately double that seen in NL. These results indicate that ICcc neurons perform a computation functionally analogous to averaging across a population of similarly tuned NL neurons.

Interdependent effects of sound duration and amplitude on neuronal onset response in mice inferior colliculus.

PubMed

Wang, Ningqian; Wang, Xiao; Yang, Xiaoli; Tang, Jie; Xiao, Zhongju

2014-01-16

In this study, we adopted iso-frequency pure tone bursts to investigate the interdependent effects of sound amplitude/intensity and duration on mice inferior colliculus (IC) neuronal onset responses. On the majority of the sampled neurons (n=57, 89.1%), sound amplitude and duration had effects on the neuronal response to each other by showing complex changes of the rat-intensity function/duration selectivity types and/or best amplitudes (BAs)/durations (BDs), evaluated by spike counts. These results suggested that the balance between the excitatory and inhibitory inputs set by one acoustic parameter, amplitude or duration, affected the neuronal spike counts responses to the other. Neuronal duration selectivity types were altered easily by the low-amplitude sounds while the changes of rate-intensity function types had no obvious preferred stimulus durations. However, the first spike latencies (FSLs) of the onset response neurons were relative stable to iso-amplitude sound durations and changing systematically along with the sound levels. The superimposition of FSL and duration threshold (DT) as a function of stimulus amplitude after normalization indicated that the effects of the sound levels on FSLs are considered on DT actually. © 2013 Published by Elsevier B.V.

Electrical stimulation or MK-801 in the inferior colliculus improve motor deficits in MPTP-treated mice.

PubMed

Melo-Thomas, L; Gil-Martínez, A L; Cuenca, L; Estrada, C; Gonzalez-Cuello, A; Schwarting, R K; Herrero, M T

2018-03-01

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (p < 0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment. Copyright © 2018 Elsevier B.V. All rights reserved.

Excitatory, inhibitory and facilitatory frequency response areas in the inferior colliculus of hearing impaired mice.

PubMed

Felix, Richard A; Portfors, Christine V

2007-06-01

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after age-related high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed non-linear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory system's ability to process complex sounds such as speech.

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

Plasticity of serotonergic innervation of the inferior colliculus in mice following acoustic trauma

PubMed Central

Papesh, Melissa A.; Hurley, Laura M.

2012-01-01

Acoustic trauma often results in permanent damage to the cochlea, triggering changes in processing within central auditory structures such as the inferior colliculus (IC). The serotonergic neuromodulatory system, present in the IC, is responsive to chronic changes in the activity of sensory systems. The current study investigated whether the density of serotonergic innervation in the IC is changed following acoustic trauma. The trauma stimulus consisted of an 8 kHz pure tone presented at a level of 113 dB SPL for six consecutive hours to anesthetized CBA/J mice. Following a minimum recovery period of three weeks, serotonergic fibers were visualized via histochemical techniques targeting the serotonin reuptake transporter (SERT) and quantified using stereologic probes. SERT-positive fiber densities were then compared between the traumatized and protected hemispheres of unilaterally traumatized subjects and those of controls. A significant effect of acoustic trauma was found between the hemispheres of unilaterally traumatized subjects such that the IC contralateral to the ear of exposure contained a lower density of SERT-positive fibers than the IC ipsilateral to acoustic trauma. No significant difference in density was found between the hemispheres of control subjects. Additional dimensions of variability in serotonergic fibers were seen among subdivisions of the IC and with age. The central IC had a slightly but significantly lowered density of serotonergic fibers than other subdivisions of the IC, and serotonergic fibers also declined with age. Overall, the results indicate that acoustic trauma is capable of producing modest but significant decreases in the density of serotonergic fibers innervating the IC. PMID:22101024

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

Mechanisms of spectral and temporal integration in the mustached bat inferior colliculus

PubMed Central

Wenstrup, Jeffrey James; Nataraj, Kiran; Sanchez, Jason Tait

2012-01-01

This review describes mechanisms and circuitry underlying combination-sensitive response properties in the auditory brainstem and midbrain. Combination-sensitive neurons, performing a type of auditory spectro-temporal integration, respond to specific, properly timed combinations of spectral elements in vocal signals and other acoustic stimuli. While these neurons are known to occur in the auditory forebrain of many vertebrate species, the work described here establishes their origin in the auditory brainstem and midbrain. Focusing on the mustached bat, we review several major findings: (1) Combination-sensitive responses involve facilitatory interactions, inhibitory interactions, or both when activated by distinct spectral elements in complex sounds. (2) Combination-sensitive responses are created in distinct stages: inhibition arises mainly in lateral lemniscal nuclei of the auditory brainstem, while facilitation arises in the inferior colliculus (IC) of the midbrain. (3) Spectral integration underlying combination-sensitive responses requires a low-frequency input tuned well below a neuron's characteristic frequency (ChF). Low-ChF neurons in the auditory brainstem project to high-ChF regions in brainstem or IC to create combination sensitivity. (4) At their sites of origin, both facilitatory and inhibitory combination-sensitive interactions depend on glycinergic inputs and are eliminated by glycine receptor blockade. Surprisingly, facilitatory interactions in IC depend almost exclusively on glycinergic inputs and are largely independent of glutamatergic and GABAergic inputs. (5) The medial nucleus of the trapezoid body (MNTB), the lateral lemniscal nuclei, and the IC play critical roles in creating combination-sensitive responses. We propose that these mechanisms, based on work in the mustached bat, apply to a broad range of mammals and other vertebrates that depend on temporally sensitive integration of information across the audible spectrum. PMID:23109917

Nonlinear processing of a multicomponent communication signal by combination-sensitive neurons in the anuran inferior colliculus.

PubMed

Lee, Norman; Schrode, Katrina M; Bee, Mark A

2017-09-01

Diverse animals communicate using multicomponent signals. How a receiver's central nervous system integrates multiple signal components remains largely unknown. We investigated how female green treefrogs (Hyla cinerea) integrate the multiple spectral components present in male advertisement calls. Typical calls have a bimodal spectrum consisting of formant-like low-frequency (~0.9 kHz) and high-frequency (~2.7 kHz) components that are transduced by different sensory organs in the inner ear. In behavioral experiments, only bimodal calls reliably elicited phonotaxis in no-choice tests, and they were selectively chosen over unimodal calls in two-alternative choice tests. Single neurons in the inferior colliculus of awake, passively listening subjects were classified as combination-insensitive units (27.9%) or combination-sensitive units (72.1%) based on patterns of relative responses to the same bimodal and unimodal calls. Combination-insensitive units responded similarly to the bimodal call and one or both unimodal calls. In contrast, combination-sensitive units exhibited both linear responses (i.e., linear summation) and, more commonly, nonlinear responses (e.g., facilitation, compressive summation, or suppression) to the spectral combination in the bimodal call. These results are consistent with the hypothesis that nonlinearities play potentially critical roles in spectral integration and in the neural processing of multicomponent communication signals.

Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant

PubMed Central

Ross, Deborah A.; Puñal, Vanessa M.; Agashe, Shruti; Dweck, Isaac; Mueller, Jerel; Grill, Warren M.; Wilson, Blake S.

2016-01-01

Understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5–80 μA, 100–300 Hz, n = 172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals' judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site compared with the reference frequency used in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site's response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency-tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts. SIGNIFICANCE STATEMENT Patients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech understanding was limited for the subjects and this limitation is thought to be partly due to challenges in

Topographic and functional neuroanatomical study of GABAergic disinhibitory striatum-nigral inputs and inhibitory nigrocollicular pathways: neural hodology recruiting the substantia nigra, pars reticulata, for the modulation of the neural activity in the inferior colliculus involved with panic-like emotions.

PubMed

Castellan-Baldan, Lissandra; da Costa Kawasaki, Mateus; Ribeiro, Sandro José; Calvo, Fabrício; Corrêa, Vani Maria Alves; Coimbra, Norberto Cysne

2006-08-01

Considering the influence of the substantia nigra on mesencephalic neurons involved with fear-induced reactions organized in rostral aspects of the dorsal midbrain, the present work investigated the topographical and functional neuroanatomy of similar influence on caudal division of the corpora quadrigemina, addressing: (a) the neural hodology connecting the neostriatum, the substantia nigra, periaqueductal gray matter and inferior colliculus (IC) neural networks; (b) the influence of the inhibitory neostriatonigral-nigrocollicular GABAergic links on the control of the defensive behavior organized in the IC. The effects of the increase or decrease of activity of nigrocollicular inputs on defensive responses elicited by either electrical or chemical stimulation of the IC were also determined. Electrolytic or chemical lesions of the substantia nigra, pars reticulata (SNpr), decreased the freezing and escape behaviors thresholds elicited by electrical stimulation of the IC, and increased the behavioral responses evoked by the GABAA blockade in the same sites of the mesencephalic tectum (MT) electrically stimulated. These findings were corroborated by similar effects caused by microinjections of the GABAA-receptor agonist muscimol in the SNpr, followed by electrical and chemical stimulations of the IC. The GABAA blockade in the SNpr caused a significant increase in the defensive behavior thresholds elicited by electrical stimulation of the IC and a decrease in the mean incidence of panic-like responses induced by microinjections of bicuculline in the mesencephalic tectum (inferior colliculus). These findings suggest that the substantia nigra receives GABAergic inputs that modulate local and also inhibitory GABAergic outputs toward the IC. In fact, neurotracing experiments with fast blue and iontophoretic microinjections of biotinylated dextran amine either into the inferior colliculus or in the reticular division of the substantia nigra demonstrated a neural link

Modular-extramodular organization in developing multisensory shell regions of the mouse inferior colliculus.

PubMed

Dillingham, Christopher H; Gay, Sean M; Behrooz, Roxana; Gabriele, Mark L

2017-12-01

The complex neuroanatomical connections of the inferior colliculus (IC) and its major subdivisions offer a juxtaposition of segregated processing streams with distinct organizational features. While the tonotopically layered central nucleus is well-documented, less is known about functional compartments in the neighboring lateral cortex (LCIC). In addition to a laminar framework, LCIC afferent-efferent patterns suggest a multimodal mosaic, consisting of a patchy modular network with surrounding extramodular domains. This study utilizes several neurochemical markers that reveal an emerging LCIC modular-extramodular microarchitecture. In newborn and post-hearing C57BL/6J and CBA/CaJ mice, histochemical and immunocytochemical stains were performed for acetylcholinesterase (AChE), nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), glutamic acid decarboxylase (GAD), cytochrome oxidase (CO), and calretinin (CR). Discontinuous layer 2 modules are positive for AChE, NADPH-d, GAD, and CO throughout the rostrocaudal LCIC. While not readily apparent at birth, discrete cell clusters emerge over the first postnatal week, yielding an identifiable modular network prior to hearing onset. Modular boundaries continue to become increasingly distinct with age, as surrounding extramodular fields remain largely negative for each marker. Alignment of modular markers in serial sections suggests each highlight the same periodic patchy network throughout the nascent LCIC. In contrast, CR patterns appear complementary, preferentially staining extramodular LCIC zones. Double-labeling experiments confirm that NADPH-d, the most consistent developmental modular marker, and CR label separate, nonoverlapping LCIC compartments. Determining how this emerging modularity may align with similar LCIC patch-matrix-like Eph/ephrin guidance patterns, and how each interface with, and potentially influence developing multimodal LCIC projection configurations is discussed. © 2017 Wiley

Convergent input from brainstem coincidence detectors onto delay-sensitive neurons in the inferior colliculus.

PubMed

McAlpine, D; Jiang, D; Shackleton, T M; Palmer, A R

1998-08-01

Responses of low-frequency neurons in the inferior colliculus (IC) of anesthetized guinea pigs were studied with binaural beats to assess their mean best interaural phase (BP) to a range of stimulating frequencies. Phase plots (stimulating frequency vs BP) were produced, from which measures of characteristic delay (CD) and characteristic phase (CP) for each neuron were obtained. The CD provides an estimate of the difference in travel time from each ear to coincidence-detector neurons in the brainstem. The CP indicates the mechanism underpinning the coincidence detector responses. A linear phase plot indicates a single, constant delay between the coincidence-detector inputs from the two ears. In more than half (54 of 90) of the neurons, the phase plot was not linear. We hypothesized that neurons with nonlinear phase plots received convergent input from brainstem coincidence detectors with different CDs. Presentation of a second tone with a fixed, unfavorable delay suppressed the response of one input, linearizing the phase plot and revealing other inputs to be relatively simple coincidence detectors. For some neurons with highly complex phase plots, the suppressor tone altered BP values, but did not resolve the nature of the inputs. For neurons with linear phase plots, the suppressor tone either completely abolished their responses or reduced their discharge rate with no change in BP. By selectively suppressing inputs with a second tone, we are able to reveal the nature of underlying binaural inputs to IC neurons, confirming the hypothesis that the complex phase plots of many IC neurons are a result of convergence from simple brainstem coincidence detectors.

Neurons in the inferior colliculus of the rat show stimulus-specific adaptation for frequency, but not for intensity

PubMed Central

Duque, Daniel; Wang, Xin; Nieto-Diego, Javier; Krumbholz, Katrin; Malmierca, Manuel S.

2016-01-01

Electrophysiological and psychophysical responses to a low-intensity probe sound tend to be suppressed by a preceding high-intensity adaptor sound. Nevertheless, rare low-intensity deviant sounds presented among frequent high-intensity standard sounds in an intensity oddball paradigm can elicit an electroencephalographic mismatch negativity (MMN) response. This has been taken to suggest that the MMN is a correlate of true change or “deviance” detection. A key question is where in the ascending auditory pathway true deviance sensitivity first emerges. Here, we addressed this question by measuring low-intensity deviant responses from single units in the inferior colliculus (IC) of anesthetized rats. If the IC exhibits true deviance sensitivity to intensity, IC neurons should show enhanced responses to low-intensity deviant sounds presented among high-intensity standards. Contrary to this prediction, deviant responses were only enhanced when the standards and deviants differed in frequency. The results could be explained with a model assuming that IC neurons integrate over multiple frequency-tuned channels and that adaptation occurs within each channel independently. We used an adaptation paradigm with multiple repeated adaptors to measure the tuning widths of these adaption channels in relation to the neurons’ overall tuning widths. PMID:27066835

Testing inferior colliculus neurons for selectivity to the rate or duration of frequency modulated sweeps

NASA Astrophysics Data System (ADS)

Faure, Paul A.; Morrison, James A.; Valdizón-Rodríguez, Roberto

2018-05-01

Here we propose a method for testing how the responses of so-called "FM duration-tuned neurons (DTNs)" encode temporal properties of frequency modulated (FM) sweeps to determine if the responses of so-called "FM duration-tuned neurons (DTNs)" are tuned to FM rate or FM duration. Based on previous studies it was unclear if the responses of "FM DTNs" were tuned to signal duration, like pure-tone DTNs, or FM sweep rate. We tested this using single-unit extracellular recording in the inferior colliculus (IC) of the big brown bat (Eptesicus fuscus). We presented IC cells with linear FM sweeps that were varied in FM center frequency (CEF) and spectral bandwidth (BW) to measure the FM rate tuning responses of a cell. We also varied FM signal duration to measure the best duration (BD) and temporal BW of duration tuning of a cell. We then doubled (and halved) the best FM BW, while keeping the CEF constant, and remeasured the BD and temporal BW of duration tuning with FM bandwidth manipulated signals. We reasoned that the range of excitatory signal durations should not change in a true FM DTN whose responses are tuned to signal duration; however, when stimulated with bandwidth manipulated FM sounds the range of excitatory signal durations should predictably vary in a FM rate-tuned cell. Preliminary data indicate that our stimulus paradigm can disambiguate whether the evoked responses of an IC neuron are FM sweep rate tuned or FM duration tuned.

ON and OFF inhibition as mechanisms for forward masking in the inferior colliculus: a modeling study

PubMed Central

2016-01-01

Masking effects of a preceding stimulus on the detection or perception of a signal have been found in several sensory systems in mammals, including humans and rodents. In the auditory system, it has been hypothesized that a central “OFF-inhibitory” mechanism, which is generated by neurons that respond after a sound is terminated, may contribute to the observed psychophysics. The present study constructed a systems model for the inferior colliculus that includes major ascending monaural and binaural auditory pathways. The fundamental characteristics of several neuron types along the pathways were captured by Hodgkin-Huxley models with specific membrane and synaptic properties. OFF responses were reproduced with a model of the superior paraolivary nucleus containing a hyperpolarization-activated h current and a T-type calcium current. When the gap between the end of the masker and the onset of the signal was large, e.g., >5 ms, OFF inhibition generated strong suppressive effects on the signal response. For smaller gaps, an additional inhibitory source, which was modeled as ON inhibition from the contralateral dorsal nucleus of the lateral lemniscus, showed the potential of explaining the psychophysics. Meanwhile, the effect of a forward masker on the binaural sensitivity to a low-frequency signal was examined, which was consistent with previous psychophysical findings related to sound localization. PMID:26912597

Decreased norepinephrine (NE) uptake in cerebral cortex and inferior colliculus of genetically epilepsy prone (GEP) rats

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

Browning, R.A.; Rigler-Daugherty, S.K.; Long, G.

1986-03-01

GEP rats are characterized by an enhanced susceptibility to seizures caused by a variety of stimuli, most notably sound. Pharmacological treatments that reduce the synaptic concentration of NE increase seizure severity in GEP rats while elevations in NE have the opposite effect. GEP rats also display a widespread deficit in brain NE concentration suggesting that their increased seizure susceptibility is related to a deficit in noradrenergic transmission. The authors have compared the kinetics of /sup 3/H-NE uptake in the P/sub 2/ synaptosomal fraction isolated from the cerebral cortex of normal and GEP-rats. Although the apparent Kms were not significantly differentmore » (Normal +/- SEM:0.37 +/- 0.13..mu..M; GEP +/- SEM: 0.29 +/- 0.07..mu..M), the Vmax for GEP rats was 48% lower than that of normal rats (Normal +/- SEM: 474 +/- 45 fmole/mg/4min; GEP +/- SEM: 248 +/- 16 fmole/mg/4min). Because of the possible role of the inferior colliculus (IC) in the initiation of sound-induced seizures in GEP rats, the authors measured synaptosomal NE uptake in the IC using a NE concentration of 50 nM. The IC synaptosomal NE uptake was found to be 35% lower in GEP than in normal rats. These findings are consistent with the hypothesis that a deficit in noradrenergic transmission is related to the increased seizure susceptibility of GEP rats.« less

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

Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat.

PubMed

Smit, Jasper V; Jahanshahi, Ali; Janssen, Marcus L F; Stokroos, Robert J; Temel, Yasin

2017-01-01

Recently it has been shown in animal studies that deep brain stimulation (DBS) of auditory structures was able to reduce tinnitus-like behavior. However, the question arises whether hearing might be impaired when interfering in auditory-related network loops with DBS. The auditory brainstem response (ABR) was measured in rats during high frequency stimulation (HFS) and low frequency stimulation (LFS) in the central nucleus of the inferior colliculus (CIC, n  = 5) or dentate cerebellar nucleus (DCBN, n  = 5). Besides hearing thresholds using ABR, relative measures of latency and amplitude can be extracted from the ABR. In this study ABR thresholds, interpeak latencies (I-III, III-V, I-V) and V/I amplitude ratio were measured during off-stimulation state and during LFS and HFS. In both the CIC and the CNBN groups, no significant differences were observed for all outcome measures. DBS in both the CIC and the CNBN did not have adverse effects on hearing measurements. These findings suggest that DBS does not hamper physiological processing in the auditory circuitry.

Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus

PubMed Central

Bandara, Suren B.; Eubig, Paul A.; Sadowski, Renee N.; Schantz, Susan L.

2016-01-01

Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. PMID:26543103

Expression of Immediate-Early Genes in the Inferior Colliculus and Auditory Cortex in Salicylate-Induced Tinnitus in Rat

PubMed Central

Hu, S.S.; Mei, L.; Chen, J.Y.; Huang, Z.W.; Wu, H.

2014-01-01

Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl D-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus. PMID:24704997

Target representation of naturalistic echolocation sequences in single unit responses from the inferior colliculus of big brown bats

NASA Astrophysics Data System (ADS)

Sanderson, Mark I.; Simmons, James A.

2005-11-01

Echolocating big brown bats (Eptesicus fuscus) emit trains of frequency-modulated (FM) biosonar signals whose duration, repetition rate, and sweep structure change systematically during interception of prey. When stimulated with a 2.5-s sequence of 54 FM pulse-echo pairs that mimic sounds received during search, approach, and terminal stages of pursuit, single neurons (N=116) in the bat's inferior colliculus (IC) register the occurrence of a pulse or echo with an average of <1 spike/sound. Individual IC neurons typically respond to only a segment of the search or approach stage of pursuit, with fewer neurons persisting to respond in the terminal stage. Composite peristimulus-time-histogram plots of responses assembled across the whole recorded population of IC neurons depict the delay of echoes and, hence, the existence and distance of the simulated biosonar target, entirely as on-response latencies distributed across time. Correlated changes in pulse duration, repetition rate, and pulse or echo amplitude do modulate the strength of responses (probability of the single spike actually occurring for each sound), but registration of the target itself remains confined exclusively to the latencies of single spikes across cells. Modeling of echo processing in FM biosonar should emphasize spike-time algorithms to explain the content of biosonar images.

The superior colliculus of the camel: a neuronal-specific nuclear protein (NeuN) and neuropeptide study

PubMed Central

Mensah-Brown, E P K; Garey, L J

2006-01-01

In this study we examined the superior colliculus of the midbrain of the one-humped (dromedary) camel, Camelus dromedarius, using Nissl staining and anti-neuronal-specific nuclear protein (NeuN) immunohistochemistry for total neuronal population as well as for the enkephalins, somatostatin (SOM) and substance P (SP). It was found that, unlike in most mammals, the superior colliculus is much larger than the inferior colliculus. The superior colliculus is concerned with visual reflexes and the co-ordination of head, neck and eye movements, which are certainly of importance to this animal with large eyes, head and neck, and apparently good vision. The basic neuronal architecture and lamination of the superior colliculus are similar to that in other mammals. However, we describe for the first time an unusually large content of neurons in the superior colliculus with strong immunoreactivity for met-enkephalin, an endogenous opioid. We classified the majority of these neurons as small (perimeters of 40–50 µm), and localized diffusely throughout the superficial grey and stratum opticum. In addition, large pyramidal-like neurons with perimeters of 100 µm and above were present in the intermediate grey layer. Large unipolar cells were located immediately dorsal to the deep grey layer. By contrast, small neurons (perimeters of 40–50 µm) immunopositive to SOM and SP were located exclusively in the superficial grey layer. We propose that this system may be associated with a pain-inhibiting pathway that has been described from the periaqueductal grey matter, juxtaposing the deep layers of the superior colliculus, to the lower brainstem and spinal cord. Such pain inhibition could be important in relation to the camel's life in the harsh environment of its native deserts, often living in very high temperatures with no shade and a diet consisting largely of thorny branches. PMID:16441568

Neural population encoding and decoding of sound source location across sound level in the rabbit inferior colliculus

PubMed Central

Delgutte, Bertrand

2015-01-01

At lower levels of sensory processing, the representation of a stimulus feature in the response of a neural population can vary in complex ways across different stimulus intensities, potentially changing the amount of feature-relevant information in the response. How higher-level neural circuits could implement feature decoding computations that compensate for these intensity-dependent variations remains unclear. Here we focused on neurons in the inferior colliculus (IC) of unanesthetized rabbits, whose firing rates are sensitive to both the azimuthal position of a sound source and its sound level. We found that the azimuth tuning curves of an IC neuron at different sound levels tend to be linear transformations of each other. These transformations could either increase or decrease the mutual information between source azimuth and spike count with increasing level for individual neurons, yet population azimuthal information remained constant across the absolute sound levels tested (35, 50, and 65 dB SPL), as inferred from the performance of a maximum-likelihood neural population decoder. We harnessed evidence of level-dependent linear transformations to reduce the number of free parameters in the creation of an accurate cross-level population decoder of azimuth. Interestingly, this decoder predicts monotonic azimuth tuning curves, broadly sensitive to contralateral azimuths, in neurons at higher levels in the auditory pathway. PMID:26490292

Inferior colliculus contributions to phase encoding of stop consonants in an animal model

PubMed Central

Warrier, Catherine M; Abrams, Daniel A; Nicol, Trent G; Kraus, Nina

2011-01-01

The human auditory brainstem is known to be exquisitely sensitive to fine-grained spectro-temporal differences between speech sound contrasts, and the ability of the brainstem to discriminate between these contrasts is important for speech perception. Recent work has described a novel method for translating brainstem timing differences in response to speech contrasts into frequency-specific phase differentials. Results from this method have shown that the human brainstem response is surprisingly sensitive to phase-differences inherent to the stimuli across a wide extent of the spectrum. Here we use an animal model of the auditory brainstem to examine whether the stimulus-specific phase signatures measured in human brainstem responses represent an epiphenomenon associated with far field (i.e., scalp-recorded) measurement of neural activity, or alternatively whether these specific activity patterns are also evident in auditory nuclei that contribute to the scalp-recorded response, thereby representing a more fundamental temporal processing phenomenon. Responses in anaesthetized guinea pigs to three minimally-contrasting consonant-vowel stimuli were collected simultaneously from the cortical surface vertex and directly from central nucleus of the inferior colliculus (ICc), measuring volume conducted neural activity and multiunit, near-field activity, respectively. Guinea pig surface responses were similar to human scalp-recorded responses to identical stimuli in gross morphology as well as phase characteristics. Moreover, surface recorded potentials shared many phase characteristics with near-field ICc activity. Response phase differences were prominent during formant transition periods, reflecting spectro-temporal differences between syllables, and showed more subtle differences during the identical steady-state periods. ICc encoded stimulus distinctions over a broader frequency range, with differences apparent in the highest frequency ranges analyzed, up to 3000 Hz

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba's Fruit Eating Bat, Carollia perspicillata.

PubMed

Beetz, M Jerome; Kordes, Sebastian; García-Rosales, Francisco; Kössl, Manfred; Hechavarría, Julio C

2017-01-01

For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units' responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams.

Effect of background noise on neuronal coding of interaural level difference cues in rat inferior colliculus

PubMed Central

Mokri, Yasamin; Worland, Kate; Ford, Mark; Rajan, Ramesh

2015-01-01

Humans can accurately localize sounds even in unfavourable signal-to-noise conditions. To investigate the neural mechanisms underlying this, we studied the effect of background wide-band noise on neural sensitivity to variations in interaural level difference (ILD), the predominant cue for sound localization in azimuth for high-frequency sounds, at the characteristic frequency of cells in rat inferior colliculus (IC). Binaural noise at high levels generally resulted in suppression of responses (55.8%), but at lower levels resulted in enhancement (34.8%) as well as suppression (30.3%). When recording conditions permitted, we then examined if any binaural noise effects were related to selective noise effects at each of the two ears, which we interpreted in light of well-known differences in input type (excitation and inhibition) from each ear shaping particular forms of ILD sensitivity in the IC. At high signal-to-noise ratios (SNR), in most ILD functions (41%), the effect of background noise appeared to be due to effects on inputs from both ears, while for a large percentage (35.8%) appeared to be accounted for by effects on excitatory input. However, as SNR decreased, change in excitation became the dominant contributor to the change due to binaural background noise (63.6%). These novel findings shed light on the IC neural mechanisms for sound localization in the presence of continuous background noise. They also suggest that some effects of background noise on encoding of sound location reported to be emergent in upstream auditory areas can also be observed at the level of the midbrain. PMID:25865218

Neurobehavioral Development of Common Marmoset Monkeys

PubMed Central

Schultz-Darken, Nancy; Braun, Katarina M.; Emborg, Marina E.

2016-01-01

Common marmoset (Callithrix jacchus) monkeys are a resource for biomedical research and their use is predicted to increase due to the suitability of this species for transgenic approaches. Identification of abnormal neurodevelopment due to genetic modification relies upon the comparison with validated patterns of normal behavior defined by unbiased methods. As scientists unfamiliar with nonhuman primate development are interested to apply genomic editing techniques in marmosets, it would be beneficial to the field that the investigators use validated methods of postnatal evaluation that are age and species appropriate. This review aims to analyze current available data on marmoset physical and behavioral postnatal development, describe the methods used and discuss next steps to better understand and evaluate marmoset normal and abnormal postnatal neurodevelopment PMID:26502294

Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus.

PubMed

Bandara, Suren B; Eubig, Paul A; Sadowski, Renee N; Schantz, Susan L

2016-02-01

Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Social isolation reduces serotonergic fiber density in the inferior colliculus of female, but not male, mice.

PubMed

Keesom, Sarah M; Morningstar, Mitchell D; Sandlain, Rebecca; Wise, Bradley M; Hurley, Laura M

2018-05-12

Early-life experiences, including maternal deprivation and social isolation during adolescence, have a profound influence on a range of adult social behaviors. Post-weaning social isolation in rodents influences behavior in part through the alteration of neuromodulatory systems, including the serotonergic system. Of significance to social behavior, the serotonergic system richly innervates brain areas involved in vocal communication, including the auditory system. However, the influence of isolation on serotonergic input to the auditory system remains underexplored. Here, we assess whether 4 weeks of post-weaning individual housing alters serotonergic fiber density in the inferior colliculus (IC), an auditory midbrain nucleus in which serotonin alters auditory-evoked activity. Individually housed male and female mice were compared to conspecifics housed socially in groups of three. Serotonergic projections were subsequently visualized with an antibody to the serotonin transporter, which labels serotonergic fibers with relatively high selectivity. Fiber densities were estimated in the three major subregions of the IC using line-scan intensity analysis. Individually housed female mice showed a significantly reduced fiber density relative to socially housed females, which was accompanied by a lower body weight in individually housed females. In contrast, social isolation did not affect serotonergic fiber density in the IC of males. This finding suggests that sensitivity of the serotonergic system to social isolation is sex-dependent, which could be due to a sex difference in the effect of isolation on psychosocial stress. Since serotonin availability depends on social context, this finding further suggests that social isolation can alter the acute social regulation of auditory processing. Copyright © 2018. Published by Elsevier B.V.

Intralaminar stimulation of the inferior colliculus facilitates frequency-specific activation in the auditory cortex

NASA Astrophysics Data System (ADS)

Allitt, B. J.; Benjaminsen, C.; Morgan, S. J.; Paolini, A. G.

2013-08-01

Objective. Auditory midbrain implants (AMI) provide inadequate frequency discrimination for open set speech perception. AMIs that can take advantage of the tonotopic laminar of the midbrain may be able to better deliver frequency specific perception and lead to enhanced performance. Stimulation strategies that best elicit frequency specific activity need to be identified. This research examined the characteristic frequency (CF) relationship between regions of the auditory cortex (AC), in response to stimulated regions of the inferior colliculus (IC), comparing monopolar, and intralaminar bipolar electrical stimulation. Approach. Electrical stimulation using multi-channel micro-electrode arrays in the IC was used to elicit AC responses in anaesthetized male hooded Wistar rats. The rate of activity in AC regions with CFs within 3 kHz (CF-aligned) and unaligned CFs was used to assess the frequency specificity of responses. Main results. Both monopolar and bipolar IC stimulation led to CF-aligned neural activity in the AC. Altering the distance between the stimulation and reference electrodes in the IC led to changes in both threshold and dynamic range, with bipolar stimulation with 400 µm spacing evoking the lowest AC threshold and widest dynamic range. At saturation, bipolar stimulation elicited a significantly higher mean spike count in the AC at CF-aligned areas than at CF-unaligned areas when electrode spacing was 400 µm or less. Bipolar stimulation using electrode spacing of 400 µm or less also elicited a higher rate of elicited activity in the AC in both CF-aligned and CF-unaligned regions than monopolar stimulation. When electrodes were spaced 600 µm apart no benefit over monopolar stimulation was observed. Furthermore, monopolar stimulation of the external cortex of the IC resulted in more localized frequency responses than bipolar stimulation when stimulation and reference sites were 200 µm apart. Significance. These findings have implications for the

Cortical Auditory Deafferentation Induces Long-Term Plasticity in the Inferior Colliculus of Adult Rats: Microarray and qPCR Analysis

PubMed Central

Clarkson, Cheryl; Herrero-Turrión, M. Javier; Merchán, Miguel A.

2012-01-01

The cortico-collicular pathway is a bilateral excitatory projection from the cortex to the inferior colliculus (IC). It is asymmetric and predominantly ipsilateral. Using microarrays and RT-qPCR we analyzed changes in gene expression in the IC after unilateral lesions of the auditory cortex, comparing the ICs ipsi- and contralateral to the lesioned side. At 15 days after surgery there were mainly changes in gene expression in the IC ipsilateral to the lesion. Regulation primarily involved inflammatory cascade genes, suggesting a direct effect of degeneration rather than a neuronal plastic reorganization. Ninety days after the cortical lesion the ipsilateral IC showed a significant up-regulation of genes involved in apoptosis and axonal regeneration combined with a down-regulation of genes involved in neurotransmission, synaptic growth, and gap junction assembly. In contrast, the contralateral IC at 90 days post-lesion showed an up-regulation in genes primarily related to neurotransmission, cell proliferation, and synaptic growth. There was also a down-regulation in autophagy and neuroprotection genes. These findings suggest that the reorganization in the IC after descending pathway deafferentation is a long-term process involving extensive changes in gene expression regulation. Regulated genes are involved in many different neuronal functions, and the number and gene rearrangement profile seems to depend on the density of loss of the auditory cortical inputs. PMID:23233834

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba’s Fruit Eating Bat, Carollia perspicillata

PubMed Central

Kordes, Sebastian; Kössl, Manfred

2017-01-01

Abstract For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units’ responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams. PMID:29242823

Circuits that Innervate Excitatory-Inhibitory Cells in the Inferior Colliculus Obtained with In-Vivo Whole Cell Recordings

PubMed Central

Li, Na; Pollak, George D.

2013-01-01

Neurons excited by stimulation of one ear and suppressed by the other, called EI neurons, are sensitive to interaural intensity disparities (IIDs), the cues animals use to localize high frequencies. EI neurons are first formed in lateral superior olive (LSO), which then sends excitatory projections to the dorsal nucleus of the lateral lemniscus (DNLL) and the inferior colliculus (IC), both of which contain large populations of EI cells. We evaluate the inputs that innervate EI cells in the IC of Mexican free-tailed bats, Tadarida brasilensis mexicana, with in vivo whole cell recordings from which we derived excitatory and inhibitory conductances. We show that the basic EI property in the majority of IC cells is inherited from LSO, but each type of EI cell is also innervated by the ipsi- or contralateral DNLL, as well as additional excitatory and inhibitory inputs from monaural nuclei. We identify three EI types, where each type receives a set of projections that are different from the other types. To evaluate the role that the various projections played in generating binaural responses, we used modeling to compute a predicted response from the conductances. We then omitted one of the conductances from the computation to evaluate the degree to which that input contributed to the binaural response. We show that formation of the EI property in the various types is complex, and that some projections exert such subtle influences that they could not have been detected with extracellular recordings or even from intracellular recordings of post-synaptic potentials. PMID:23575835

Marmosets: A Neuroscientific Model of Human Social Behavior

PubMed Central

Freiwald, Winrich A; Leopold, David A; Mitchell, Jude F; Silva, Afonso C; Wang, Xiaoqin

2016-01-01

The common marmoset (Callithrix jacchus) has garnered interest recently as a powerful model for the future of neuroscience research. Much of this excitement has centered on the species’ reproductive biology and compatibility with gene editing techniques, which together have provided a path for transgenic marmosets to contribute to the study of disease as well as basic brain mechanisms. In step with technical advances is the need to establish experimental paradigms that optimally tap into the marmosets’ behavioral and cognitive capacities. While conditioned task performance of a marmoset can compare unfavorably with rhesus monkey performance on conventional testing paradigms, marmosets’ social cognition and communication are more similar to that of humans. For example, marmosets are amongst only a handful of primates that, like humans, routinely pair bond and care cooperatively for their young. They are also notably pro-social and exhibit social cognitive abilities, such as imitation, that are rare outside of the Apes. In this review, we describe key facets of marmoset natural social behavior and demonstrate that emerging behavioral paradigms are well suited to isolate components of marmoset cognition that are highly relevant to humans. These approaches generally embrace natural behavior and communication, which has been rare in conventional primate testing, and thus allow for a new consideration of neural mechanisms underlying primate social cognition and communication. We anticipate that through parallel technical and paradigmatic advances, marmosets will become an essential model of human social behavior, including its dysfunction in nearly all neuropsychiatric disorders. PMID:27100195

Cognitive bias, hand preference and welfare of common marmosets.

PubMed

Gordon, Dianne J; Rogers, Lesley J

2015-01-01

Common marmosets (Callithrix jacchus) have hand preferences for grasping pieces of food and holding them while eating and these are stable throughout adult life. We report here that left-handed marmosets have negative cognitive bias compared to right-handed marmosets. Twelve marmosets were trained to expect a food reward from a bowl with a black lid and not from one with a white lid, or vice versa. In probe tests with ambiguous, grey-lidded bowls a left-handed group (N=7) were less likely to remove the lid to inspect the bowl than a right-handed group (N=5). This difference between left- and right-handed marmosets was not dependent on rate of learning, sex or age. In fact, hand-preference was not associated with rate of learning the task. Furthermore, retrospective examination of colony records of 39 marmosets revealed that more aggression was directed towards left- than right-handed marmosets. Hence, hand preference, which can be measured easily, could serve as an indicator of cognitive bias and may signal a need for particular care in laboratory environments. We explain the results by arguing that hand preference reflects more frequent (or dominant) use of the opposite hemisphere and this predisposes individuals to behave differently. Copyright © 2015 Elsevier B.V. All rights reserved.

[Effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking method on auditory brainstem response and neurotransmitters of inferior colliculus in rats of tinnitus].

PubMed

Yang, Songbai; Mei, Zhigang; Tan, Lingjing; Ma, Wenhan; Zhang, Dingqi; Wang, Zhaojun; Li, Tiantian; Huang, Kunyan; Cai, Sanjin

2016-05-01

To explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats. Twenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared. Compared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in

Dual sensitivity of inferior colliculus neurons to ITD in the envelopes of high-frequency sounds: experimental and modeling study

PubMed Central

Wang, Le; Devore, Sasha; Delgutte, Bertrand

2013-01-01

Human listeners are sensitive to interaural time differences (ITDs) in the envelopes of sounds, which can serve as a cue for sound localization. Many high-frequency neurons in the mammalian inferior colliculus (IC) are sensitive to envelope-ITDs of sinusoidally amplitude-modulated (SAM) sounds. Typically, envelope-ITD-sensitive IC neurons exhibit either peak-type sensitivity, discharging maximally at the same delay across frequencies, or trough-type sensitivity, discharging minimally at the same delay across frequencies, consistent with responses observed at the primary site of binaural interaction in the medial and lateral superior olives (MSO and LSO), respectively. However, some high-frequency IC neurons exhibit dual types of envelope-ITD sensitivity in their responses to SAM tones, that is, they exhibit peak-type sensitivity at some modulation frequencies and trough-type sensitivity at other frequencies. Here we show that high-frequency IC neurons in the unanesthetized rabbit can also exhibit dual types of envelope-ITD sensitivity in their responses to SAM noise. Such complex responses to SAM stimuli could be achieved by convergent inputs from MSO and LSO onto single IC neurons. We test this hypothesis by implementing a physiologically explicit, computational model of the binaural pathway. Specifically, we examined envelope-ITD sensitivity of a simple model IC neuron that receives convergent inputs from MSO and LSO model neurons. We show that dual envelope-ITD sensitivity emerges in the IC when convergent MSO and LSO inputs are differentially tuned for modulation frequency. PMID:24155013

Comparison of bandwidths in the inferior colliculus and the auditory nerve. II: Measurement using a temporally manipulated stimulus.

PubMed

Mc Laughlin, Myles; Chabwine, Joelle Nsimire; van der Heijden, Marcel; Joris, Philip X

2008-10-01

To localize low-frequency sounds, humans rely on an interaural comparison of the temporally encoded sound waveform after peripheral filtering. This process can be compared with cross-correlation. For a broadband stimulus, after filtering, the correlation function has a damped oscillatory shape where the periodicity reflects the filter's center frequency and the damping reflects the bandwidth (BW). The physiological equivalent of the correlation function is the noise delay (ND) function, which is obtained from binaural cells by measuring response rate to broadband noise with varying interaural time delays (ITDs). For monaural neurons, delay functions are obtained by counting coincidences for varying delays across spike trains obtained to the same stimulus. Previously, we showed that BWs in monaural and binaural neurons were similar. However, earlier work showed that the damping of delay functions differs significantly between these two populations. Here, we address this paradox by looking at the role of sensitivity to changes in interaural correlation. We measured delay and correlation functions in the cat inferior colliculus (IC) and auditory nerve (AN). We find that, at a population level, AN and IC neurons with similar characteristic frequencies (CF) and BWs can have different responses to changes in correlation. Notably, binaural neurons often show compression, which is not found in the AN and which makes the shape of delay functions more invariant with CF at the level of the IC than at the AN. We conclude that binaural sensitivity is more dependent on correlation sensitivity than has hitherto been appreciated and that the mechanisms underlying correlation sensitivity should be addressed in future studies.

Tonotopic reorganization and spontaneous firing in inferior colliculus during both short and long recovery periods after noise overexposure

PubMed Central

2013-01-01

Background Noise induced injury of the cochlea causes shifts in activation thresholds and changes of frequency response in the inferior colliculus (IC). Noise overexposure also induces pathological changes in the cochlea, and is highly correlated to hearing loss. However, the underlying mechanism has not been fully elucidated. In this study, we hypothesized that overexposure to noise induces substantial electrophysiological changes in the IC of guinea pigs. Results During the noise exposure experiment, the animals were undergoing a bilateral exposure to noise. Additionally, various techniques were employed including confocal microscopy for the detection of cochlea hair cells and single neuron recording for spontaneous firing activity measurement. There were alterations among three types of frequency response area (FRA) from sound pressure levels, including V-, M-, and N-types. Our results indicate that overexposure to noise generates different patterns in the FRAs. Following a short recovery (one day after the noise treatment), the percentage of V-type FRAs considerably decreased, whereas the percentage of M-types increased. This was often caused by a notch in the frequency response that occurred at 4 kHz (noise frequency). Following a long recovery from noise exposure (11–21 days), the percentage of V-types resumed to a normal level, but the portion of M-types remained high. Interestingly, the spontaneous firing in the IC was enhanced in both short and long recovery groups. Conclusion Our data suggest that noise overexposure changes the pattern of the FRAs and stimulates spontaneous firing in the IC in a unique way, which may likely relate to the mechanism of tinnitus. PMID:24320109

Local Application of Sodium Salicylate Enhances Auditory Responses in the Rat’s Dorsal Cortex of the Inferior Colliculus

PubMed Central

Patel, Chirag R.; Zhang, Huiming

2014-01-01

Sodium salicylate (SS) is a widely used medication with side effects on hearing. In order to understand these side effects, we recorded sound-driven local-field potentials in a neural structure, the dorsal cortex of the inferior colliculus (ICd). Using a microiontophoretic technique, we applied SS at sites of recording and studied how auditory responses were affected by the drug. Furthermore, we studied how the responses were affected by combined local application of SS and an agonists/antagonist of the type-A or type-B γ-aminobutyric acid receptor (GABAA or GABAB receptor). Results revealed that SS applied alone enhanced auditory responses in the ICd, indicating that the drug had local targets in the structure. Simultaneous application of the drug and a GABAergic receptor antagonist synergistically enhanced amplitudes of responses. The synergistic interaction between SS and a GABAA receptor antagonist had a relatively early start in reference to the onset of acoustic stimulation and the duration of this interaction was independent of sound intensity. The interaction between SS and a GABAB receptor antagonist had a relatively late start, and the duration of this interaction was dependent on sound intensity. Simultaneous application of the drug and a GABAergic receptor agonist produced an effect different from the sum of effects produced by the two drugs released individually. These differences between simultaneous and individual drug applications suggest that SS modified GABAergic inhibition in the ICd. Our results indicate that SS can affect sound-driven activity in the ICd by modulating local GABAergic inhibition. PMID:25452744

Frequency tuning of synaptic inhibition underlying duration-tuned neurons in the mammalian inferior colliculus

PubMed Central

Valdizón-Rodríguez, Roberto

2017-01-01

Inhibition plays an important role in creating the temporal response properties of duration-tuned neurons (DTNs) in the mammalian inferior colliculus (IC). Neurophysiological and computational studies indicate that duration selectivity in the IC is created through the convergence of excitatory and inhibitory synaptic inputs offset in time. We used paired-tone stimulation and extracellular recording to measure the frequency tuning of the inhibition acting on DTNs in the IC of the big brown bat (Eptesicus fuscus). We stimulated DTNs with pairs of tones differing in duration, onset time, and frequency. The onset time of a short, best-duration (BD), probe tone set to the best excitatory frequency (BEF) was varied relative to the onset of a longer-duration, nonexcitatory (NE) tone whose frequency was varied. When the NE tone frequency was near or within the cell’s excitatory bandwidth (eBW), BD tone-evoked spikes were suppressed by an onset-evoked inhibition. The onset of the spike suppression was independent of stimulus frequency, but both the offset and duration of the suppression decreased as the NE tone frequency departed from the BEF. We measured the inhibitory frequency response area, best inhibitory frequency (BIF), and inhibitory bandwidth (iBW) of each cell. We found that the BIF closely matched the BEF, but the iBW was broader and usually overlapped the eBW measured from the same cell. These data suggest that temporal selectivity of midbrain DTNs is created and preserved by having cells receive an onset-evoked, constant-latency, broadband inhibition that largely overlaps the cell’s excitatory receptive field. We conclude by discussing possible neural sources of the inhibition. NEW & NOTEWORTHY Duration-tuned neurons (DTNs) arise from temporally offset excitatory and inhibitory synaptic inputs. We used single-unit recording and paired-tone stimulation to measure the spectral tuning of the inhibitory inputs to DTNs. The onset of inhibition was independent of

The marmoset monkey as a model for visual neuroscience

PubMed Central

Mitchell, Jude F.; Leopold, David A.

2015-01-01

The common marmoset (Callithrix jacchus) has been valuable as a primate model in biomedical research. Interest in this species has grown recently, in part due to the successful demonstration of transgenic marmosets. Here we examine the prospects of the marmoset model for visual neuroscience research, adopting a comparative framework to place the marmoset within a broader evolutionary context. The marmoset’s small brain bears most of the organizational features of other primates, and its smooth surface offers practical advantages over the macaque for areal mapping, laminar electrode penetration, and two-photon and optical imaging. Behaviorally, marmosets are more limited at performing regimented psychophysical tasks, but do readily accept the head restraint that is necessary for accurate eye tracking and neurophysiology, and can perform simple discriminations. Their natural gaze behavior closely resembles that of other primates, with a tendency to focus on objects of social interest including faces. Their immaturity at birth and routine twinning also makes them ideal for the study of postnatal visual development. These experimental factors, together with the theoretical advantages inherent in comparing anatomy, physiology, and behavior across related species, make the marmoset an excellent model for visual neuroscience. PMID:25683292

Do marmosets care to share? Oxytocin treatment reduces prosocial behavior toward strangers

PubMed Central

Mustoe, Aaryn C.; Cavanaugh, Jon; Harnisch, April M.; Thompson, Breanna E.; French, Jeffrey A.

2015-01-01

Cooperatively-breeding and socially-monogamous primates, like marmosets and humans, exhibit high levels of social tolerance and prosociality toward others. Oxytocin (OXT) generally facilitates prosocial behavior, but there is growing recognition that OXT modulation of prosocial behavior is shaped by the context of social interactions and by other motivational states such as arousal or anxiety. To determine whether prosociality varies based on social context, we evaluated whether marmoset donors (Callithrix penicillata) preferentially rewarded pairmates versus opposite-sex strangers in a prosocial food-sharing task. To examine potential links among OXT, stress systems, and prosociality, we evaluated whether pretrial cortisol levels in marmosets altered the impact of OXT on prosocial responses. Marmosets exhibited spontaneous prosociality toward others, but they did so preferentially toward strangers compared to their pairmates. When donor marmosets were treated with marmoset-specific Pro8-OXT, they exhibited reduced prosociality toward strangers compared to marmosets treated with saline or consensus-mammalian Leu8-OXT. When pretrial cortisol levels were lower, marmosets exhibited higher prosociality toward strangers. These findings demonstrate that while marmosets show spontaneous prosocial responses toward others, they do so preferentially toward opposite-sex strangers. Cooperative breeding may be associated with the expression of prosociality, but the existence of a pair-bond between marmoset partners appears to be neither necessary nor sufficient for the expression of spontaneous prosocial responses. Further, high prosociality toward strangers is significantly reduced in marmosets treated with Pro8-OXT, suggesting that OXT does not universally enhance prosociality, but, rather OXT modulation of prosocial behavior varies depending on social context. PMID:25934057

Limiting parental feedback disrupts vocal development in marmoset monkeys

PubMed Central

Gultekin, Yasemin B.; Hage, Steffen R.

2017-01-01

Vocalizations of human infants undergo dramatic changes across the first year by becoming increasingly mature and speech-like. Human vocal development is partially dependent on learning by imitation through social feedback between infants and caregivers. Recent studies revealed similar developmental processes being influenced by parental feedback in marmoset monkeys for apparently innate vocalizations. Marmosets produce infant-specific vocalizations that disappear after the first postnatal months. However, it is yet unclear whether parental feedback is an obligate requirement for proper vocal development. Using quantitative measures to compare call parameters and vocal sequence structure we show that, in contrast to normally raised marmosets, marmosets that were separated from parents after the third postnatal month still produced infant-specific vocal behaviour at subadult stages. These findings suggest a significant role of social feedback on primate vocal development until the subadult stages and further show that marmoset monkeys are a compelling model system for early human vocal development. PMID:28090084

Recovery cycle times of inferior colliculus neurons in the awake bat measured with spike counts and latencies

PubMed Central

Sayegh, Riziq; Aubie, Brandon; Fazel-Pour, Siavosh; Faure, Paul A.

2012-01-01

Neural responses in the mammalian auditory midbrain (inferior colliculus; IC) arise from complex interactions of synaptic excitation, inhibition, and intrinsic properties of the cell. Temporally selective duration-tuned neurons (DTNs) in the IC are hypothesized to arise through the convergence of excitatory and inhibitory synaptic inputs offset in time. Synaptic inhibition can be inferred from extracellular recordings by presenting pairs of pulses (paired tone stimulation) and comparing the evoked responses of the cell to each pulse. We obtained single unit recordings from the IC of the awake big brown bat (Eptesicus fuscus) and used paired tone stimulation to measure the recovery cycle times of DTNs and non-temporally selective auditory neurons. By systematically varying the interpulse interval (IPI) of the paired tone stimulus, we determined the minimum IPI required for a neuron's spike count or its spike latency (first- or last-spike latency) in response to the second tone to recover to within ≥50% of the cell's baseline count or to within 1 SD of it's baseline latency in response to the first tone. Recovery times of shortpass DTNs were significantly shorter than those of bandpass DTNs, and recovery times of bandpass DTNs were longer than allpass neurons not selective for stimulus duration. Recovery times measured with spike counts were positively correlated with those measured with spike latencies. Recovery times were also correlated with first-spike latency (FSL). These findings, combined with previous studies on duration tuning in the IC, suggest that persistent inhibition is a defining characteristic of DTNs. Herein, we discuss measuring recovery times of neurons with spike counts and latencies. We also highlight how persistent inhibition could determine neural recovery times and serve as a potential mechanism underlying the precedence effect in humans. Finally, we explore implications of recovery times for DTNs in the context of bat hearing and

Neural Correlates and Mechanisms of Spatial Release From Masking: Single-Unit and Population Responses in the Inferior Colliculus

PubMed Central

Lane, Courtney C.; Delgutte, Bertrand

2007-01-01

Spatial release from masking (SRM), a factor in listening in noisy environments, is the improvement in auditory signal detection obtained when a signal is separated in space from a masker. To study the neural mechanisms of SRM, we recorded from single units in the inferior colliculus (IC) of barbiturate-anesthetized cats, focusing on low-frequency neurons sensitive to interaural time differences. The stimulus was a broadband chirp train with a 40-Hz repetition rate in continuous broadband noise, and the unit responses were measured for several signal and masker (virtual) locations. Masked thresholds (the lowest signal-to-noise ratio, SNR, for which the signal could be detected for 75% of the stimulus presentations) changed systematically with signal and masker location. Single-unit thresholds did not necessarily improve with signal and masker separation; instead, they tended to reflect the units’ azimuth preference. Both how the signal was detected (through a rate increase or decrease) and how the noise masked the signal response (suppressive or excitatory masking) changed with signal and masker azimuth, consistent with a cross-correlator model of binaural processing. However, additional processing, perhaps related to the signal’s amplitude modulation rate, appeared to influence the units’ responses. The population masked thresholds (the most sensitive unit’s threshold at each signal and masker location) did improve with signal and masker separation as a result of the variety of azimuth preferences in our unit sample. The population thresholds were similar to human behavioral thresholds in both SNR value and shape, indicating that these units may provide a neural substrate for low-frequency SRM. PMID:15857966

Do marmosets care to share? Oxytocin treatment reduces prosocial behavior toward strangers.

PubMed

Mustoe, Aaryn C; Cavanaugh, Jon; Harnisch, April M; Thompson, Breanna E; French, Jeffrey A

2015-05-01

Cooperatively-breeding and socially-monogamous primates, like marmosets and humans, exhibit high levels of social tolerance and prosociality toward others. Oxytocin (OXT) generally facilitates prosocial behavior, but there is growing recognition that OXT modulation of prosocial behavior is shaped by the context of social interactions and by other motivational states such as arousal or anxiety. To determine whether prosociality varies based on social context, we evaluated whether marmoset donors (Callithrix penicillata) preferentially rewarded pairmates versus opposite-sex strangers in a prosocial food-sharing task. To examine potential links among OXT, stress systems, and prosociality, we evaluated whether pretrial cortisol levels in marmosets altered the impact of OXT on prosocial responses. Marmosets exhibited spontaneous prosociality toward others, but they did so preferentially toward strangers compared to their pairmates. When donor marmosets were treated with marmoset-specific Pro(8)-OXT, they exhibited reduced prosociality toward strangers compared to marmosets treated with saline or consensus-mammalian Leu(8)-OXT. When pretrial cortisol levels were lower, marmosets exhibited higher prosociality toward strangers. These findings demonstrate that while marmosets show spontaneous prosocial responses toward others, they do so preferentially toward opposite-sex strangers. Cooperative breeding may be associated with the expression of prosociality, but the existence of a pair-bond between marmoset partners appears to be neither necessary nor sufficient for the expression of spontaneous prosocial responses. Furthermore, high prosociality toward strangers is significantly reduced in marmosets treated with Pro(8)-OXT, suggesting that OXT does not universally enhance prosociality, but, rather OXT modulation of prosocial behavior varies depending on social context. Copyright © 2015 Elsevier Inc. All rights reserved.

Audiogenic seizure activity following HSV-1 GAD65 sense or antisense injection into inferior colliculus of Long-Evans rat.

PubMed

Coleman, James R; Thompson, Karen C; Wilson, Marlene A; Wilson, Steven P

2017-06-01

Herpes virus technology involving manipulation of GAD65 was used to study effects on audiogenic seizures (AGS). Audiogenic seizure behaviors were examined following injections of replication-defective herpes simplex virus (HSV-1) vectors incorporating sense or antisense toward GAD65 along with 10% lac-Z into the central nucleus of inferior colliculus (CNIC) of Long-Evans rats. In seizure-sensitive animals developmentally primed by intense sound exposure, injection of GAD65 in the sense orientation increased wild running latencies and reduced incidence of clonus compared with lac-Z only, unoperated, and vehicle seizure groups. In contrast, infection of CNIC with GAD65 antisense virus resulted in 100% incidence of wild running and clonus behaviors in AGS animals. Unprimed animals not operated continued to show uniform absence of seizure activity. Administration of GAD65 antisense virus into CNIC produced novel wild running and clonus behaviors in some unprimed animals. Staining for β-galactosidase in all vector animals revealed no differences in pattern or numbers of immunoreactive cells at injection sites. Qualitatively, typical small and medium multipolar/stellate and medium fusiform neurons appeared in the CNIC of vector animals. These results demonstrate that HSV-1 vector constructs implanted into the CNIC can predictably influence incidence and severity of AGS and suggest that viral vectors can be useful in studying GABA mechanisms with potential for therapeutic application in epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2016 Elsevier Inc. All rights reserved.

Neural coding of time-varying interaural time differences and time-varying amplitude in the inferior colliculus

PubMed Central

2017-01-01

Binaural cues occurring in natural environments are frequently time varying, either from the motion of a sound source or through interactions between the cues produced by multiple sources. Yet, a broad understanding of how the auditory system processes dynamic binaural cues is still lacking. In the current study, we directly compared neural responses in the inferior colliculus (IC) of unanesthetized rabbits to broadband noise with time-varying interaural time differences (ITD) with responses to noise with sinusoidal amplitude modulation (SAM) over a wide range of modulation frequencies. On the basis of prior research, we hypothesized that the IC, one of the first stages to exhibit tuning of firing rate to modulation frequency, might use a common mechanism to encode time-varying information in general. Instead, we found weaker temporal coding for dynamic ITD compared with amplitude modulation and stronger effects of adaptation for amplitude modulation. The differences in temporal coding of dynamic ITD compared with SAM at the single-neuron level could be a neural correlate of “binaural sluggishness,” the inability to perceive fluctuations in time-varying binaural cues at high modulation frequencies, for which a physiological explanation has so far remained elusive. At ITD-variation frequencies of 64 Hz and above, where a temporal code was less effective, noise with a dynamic ITD could still be distinguished from noise with a constant ITD through differences in average firing rate in many neurons, suggesting a frequency-dependent tradeoff between rate and temporal coding of time-varying binaural information. NEW & NOTEWORTHY Humans use time-varying binaural cues to parse auditory scenes comprising multiple sound sources and reverberation. However, the neural mechanisms for doing so are poorly understood. Our results demonstrate a potential neural correlate for the reduced detectability of fluctuations in time-varying binaural information at high speeds, as occurs

Bone Disease in the Common Marmoset: Radiographic and Histological Findings.

PubMed

Olson, E J; Shaw, G C; Hutchinson, E K; Schultz-Darken, N; Bolton, I D; Parker, J B; Morrison, J M; Baxter, V K; Pate, K A Metcalf; Mankowski, J L; Carlson, C S

2015-09-01

The common marmoset (Callithrix jacchus) is a New World primate that is used in biomedical research due to its small size and relative ease of handling compared with larger primates. Although bone disease in common marmosets is well recognized, there are very few detailed descriptions in the literature that cover the range of lesions seen in these animals. For all animals used to model human disease, it is important to be aware of background lesions that may affect the interpretation of study findings. This retrospective study details bone diseases encountered in marmoset breeding colonies at 2 different institutions. Affected marmosets at Johns Hopkins University had lesions compatible with diagnoses of rickets, fibrous osteodystrophy and osteopenia. Affected marmosets at the Wisconsin National Primate Research Center exhibited severe lesions of osteoclastic bone resorption and remodeling that had an unusual distribution and were not easily categorized into a known disease entity. The purpose of this report is to document these naturally occurring skeletal lesions of common marmosets and suggest an approach to evaluating skeletal disease in prospective studies of these animals that will allow the most accurate diagnoses. © The Author(s) 2015.

Individual variability in visual discrimination and reversal learning performance in common marmosets.

PubMed

Takemoto, Atsushi; Miwa, Miki; Koba, Reiko; Yamaguchi, Chieko; Suzuki, Hiromi; Nakamura, Katsuki

2015-04-01

Detailed information about the characteristics of learning behavior in marmosets is useful for future marmoset research. We trained 42 marmosets in visual discrimination and reversal learning. All marmosets could learn visual discrimination, and all but one could complete reversal learning, though some marmosets failed to touch the visual stimuli and were screened out. In 87% of measurements, the final percentage of correct responses was over 95%. We quantified performance with two measures: onset trial and dynamic interval. Onset trial represents the number of trials that elapsed before the marmoset started to learn. Dynamic interval represents the number of trials from the start before reaching the final percentage of correct responses. Both measures decreased drastically as a result of the formation of discrimination learning sets. In reversal learning, both measures worsened, but the effect on onset trial was far greater. The effects of age and sex were not significant as far as we used adolescent or young adult marmosets. Unexpectedly, experimental circumstance (in the colony or isolator) had only a subtle effect on performance. However, we found that marmosets from different families exhibited different learning process characteristics, suggesting some family effect on learning. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Spatial selectivity and binaural responses in the inferior colliculus of the great horned owl.

PubMed

Volman, S F; Konishi, M

1989-09-01

In this study we have investigated the processing of auditory cues for sound localization in the great horned owl (Bubo virginianus). Previous studies have shown that the barn owl, whose ears are asymmetrically oriented in the vertical plane, has a 2-dimensional, topographic representation of auditory space in the external division of the inferior colliculus (ICx). As in the barn owl, the great horned owl's ICx is anatomically distinct and projects to the optic tectum. Neurons in ICx respond over only a small range of azimuths (mean = 32 degrees), and azimuth is topographically mapped. In contrast to the barn owl, the great horned owl has bilaterally symmetrical ears and its receptive fields are not restricted in elevation. The binaural cues available for sound localization were measured both with cochlear microphonic recordings and with a microphone attached to a probe tube in the auditory canal. Interaural time disparity (ITD) varied monotonically with azimuth. Interaural intensity differences (IID) also changed with azimuth, but the largest IIDs were less than 15 dB, and the variation was not monotonic. Neither ITD nor IID varied systematically with changes in the vertical position of a sound source. We used dichotic stimulation to determine the sensitivity of ICx neurons to these binaural cues. Best ITD of ICx units was topographically mapped and strongly correlated with receptive-field azimuth. The width of ITD tuning curves, measured at 50% of the maximum response, averaged 72 microseconds. All ICx neurons responded only to binaural stimulation and had nonmonotonic IID tuning curves. Best IID was weakly, but significantly, correlated with best ITD (r = 0.39, p less than 0.05). The IID tuning curves, however, were broad (mean 50% width = 24 dB), and 67% of the units had best IIDs within 5 dB of 0 dB IID. ITD tuning was sensitive to variations in IID in the direction opposite to that expected for time-intensity trading, but the magnitude of this effect was only

Circuits for Action and Cognition: A View from the Superior Colliculus.

PubMed

Basso, Michele A; May, Paul J

2017-09-15

The superior colliculus is one of the most well-studied structures in the brain, and with each new report, its proposed role in behavior seems to increase in complexity. Forty years of evidence show that the colliculus is critical for reorienting an organism toward objects of interest. In monkeys, this involves saccadic eye movements. Recent work in the monkey colliculus and in the homologous optic tectum of the bird extends our understanding of the role of the colliculus in higher mental functions, such as attention and decision making. In this review, we highlight some of these recent results, as well as those capitalizing on circuit-based methodologies using transgenic mice models, to understand the contribution of the colliculus to attention and decision making. The wealth of information we have about the colliculus, together with new tools, provides a unique opportunity to obtain a detailed accounting of the neurons, circuits, and computations that underlie complex behavior.

Circuits for Action and Cognition: A View from the Superior Colliculus

PubMed Central

Basso, Michele A.; May, Paul J.

2017-01-01

The superior colliculus is one of the most well-studied structures in the brain, and with each new report, its proposed role in behavior seems to increase in complexity. Forty years of evidence show that the colliculus is critical for reorienting an organism toward objects of interest. In monkeys, this involves saccadic eye movements. Recent work in the monkey colliculus and in the homologous optic tectum of the bird extends our understanding of the role of the colliculus in higher mental functions, such as attention and decision making. In this review, we highlight some of these recent results, as well as those capitalizing on circuit-based methodologies using transgenic mice models, to understand the contribution of the colliculus to attention and decision making. The wealth of information we have about the colliculus, together with new tools, provides a unique opportunity to obtain a detailed accounting of the neurons, circuits, and computations that underlie complex behavior. PMID:28617660

Deep brain stimulation of the inferior colliculus: a possible animal model to study paradoxical kinesia observed in some parkinsonian patients?

PubMed

Melo-Thomas, Liana; Thomas, Uwe

2015-02-15

The inferior colliculus (IC) plays an important role in the normal processing of the acoustic message and is also involved in the filtering of acoustic stimuli of aversive nature. The neural substrate of the IC can also influence haloperidol-induced catalepsy. Considering that (i) paradoxical kinesia, observed in some parkinsonian patients, seems to be dependent of their emotional state and (ii) deep brain stimulation (DBS) represents an alternative therapeutic route for the relief of parkinsonian symptoms, the present study investigated the consequence of DBS at the IC on the catalepsy induced by haloperidol in rats. Additionally, we investigated if DBS of the IC can elicit motor responses in anesthetized rats and whether DBS elicits distinct neural firing patterns of activity at the dorsal cortex (DCIC) or central nucleus (CNIC) of the IC. A significant reduction of the catalepsy response was seen in rats previously given haloperidol and receiving DBS at the IC. In addition, electrical stimulation to the ventral part of the CNIC induced immediate motor responses in anesthetized rats. The neuronal spontaneous activity was higher at the ventral part of the CNIC than the dorsal part. DBS to the ventral part but not to the dorsal part of the CNIC increased the spike rate at neurons a few hundred microns away from the stimulation site. It is possible that the IC plays a role in the sensorimotor gating activated by emotional stimuli, and that DBS at the IC can be a promising new animal model to study paradoxical kinesia in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of Metabolic Function Biomarkers in the Common Marmoset, Callithrix jacchus

PubMed Central

Ziegler, Toni E.; Colman, Ricki J.; Tardif, Suzette D.; Sosa, Megan E.; Wegner, Fredrick H.; Wittwer, Daniel J.; Shrestha, Hemanta

2013-01-01

Metabolic assessment of a nonhuman primate model of metabolic syndrome and obesity requires the necessary biomarkers specific to the species. While the rhesus monkey has a number of specific assays for assessing metabolic syndrome, the marmoset does not. Furthermore, the common marmoset (Callithrix jacchus) has a small blood volume that necessitates using a single blood volume for multiple analyses. The common marmoset holds a great potential as an alternative primate model for the study of human disease but assay methods need to be developed and validated for the biomarkers of metabolic syndrome. Here we report on the adaptation, development and validation of commercially available immunoassays for common marmoset samples in small volumes. We have performed biological validations for insulin, adiponectin, leptin, and ghrelin to demonstrate the use of these biomarkers in examining metabolic syndrome and other related diseases in the common marmoset. PMID:23447060

Mobbing vocalizations as a coping response in the common marmoset.

PubMed

Cross, N; Rogers, L J

2006-02-01

Using a non-invasive method of sampling saliva followed by assay for cortisol levels, we found that common marmosets (Callithrix jacchus) show a decrease in cortisol levels after seeing a snake-model stimulus that reliably elicits mobbing (tsik) calls. In fact, there was a significant positive correlation between the number of tsik vocalizations made and the magnitude of the decrease in the cortisol concentrations. Furthermore, marmosets with higher levels of cortisol prior to being exposed to the stimulus produce more tsik calls than those with lower levels of cortisol. Subsequent experiments showed that, in response to 15 min of isolation with no visual or auditory contact with conspecifics (a traditional stressor), cortisol levels increased significantly. However, playback of the mobbing calls of a familiar conspecific to individual isolated marmosets not only prevented the rise in cortisol, but also actually caused a decrease in the levels of this hormone. This suggests that the mobbing calls serve to calm the marmoset after experiencing a stressful situation. This finding results in a greater understanding as to the role of physiological responses during communication in this species and could have implications for the welfare of marmosets in captivity.

A case of nontraumatic gas gangrene in a common marmoset (Callithrix jacchus).

PubMed

Yasuda, Masahiko; Inoue, Takashi; Ueno, Masami; Morita, Hanako; Hayashimoto, Nobuhito; Kawai, Kenji; Itoh, Toshio

2016-01-01

The common marmoset is widely used in neuroscience and regenerative medicine research. However, information concerning common marmoset disorders, particularly infectious diseases, is scarce. Here, we report a case of a female common marmoset that died suddenly due to gas gangrene. The animal presented with gaseous abdominal distention at postmortem, and Clostridium perfringens type A was isolated from several tissues. Vacuoles, a Gram-positive bacteremia and intravascular hemolysis were observed microscopically in the muscles, liver and lungs. On the basis of these findings, we diagnosed nontraumatic gas gangrene caused by Clostridium perfringens type A in this common marmoset.

A case of nontraumatic gas gangrene in a common marmoset (Callithrix jacchus)

PubMed Central

YASUDA, Masahiko; INOUE, Takashi; UENO, Masami; MORITA, Hanako; HAYASHIMOTO, Nobuhito; KAWAI, Kenji; ITOH, Toshio

2015-01-01

The common marmoset is widely used in neuroscience and regenerative medicine research. However, information concerning common marmoset disorders, particularly infectious diseases, is scarce. Here, we report a case of a female common marmoset that died suddenly due to gas gangrene. The animal presented with gaseous abdominal distention at postmortem, and Clostridium perfringens type A was isolated from several tissues. Vacuoles, a Gram-positive bacteremia and intravascular hemolysis were observed microscopically in the muscles, liver and lungs. On the basis of these findings, we diagnosed nontraumatic gas gangrene caused by Clostridium perfringens type A in this common marmoset. PMID:26156080

Marmosets as model species in neuroscience and evolutionary anthropology.

PubMed

Burkart, Judith M; Finkenwirth, Christa

2015-04-01

Marmosets are increasingly used as model species by both neuroscientists and evolutionary anthropologists, but with a different rationale for doing so. Whereas neuroscientists stress that marmosets share many cognitive traits with humans due to common descent, anthropologists stress those traits shared with marmosets - and callitrichid monkeys in general - due to convergent evolution, as a consequence of the cooperative breeding system that characterizes both humans and callitrichids. Similarities in socio-cognitive abilities due to convergence, rather than homology, raise the question whether these similarities also extend to the proximate regulatory mechanisms, which is particularly relevant for neuroscientific investigations. In this review, we first provide an overview of the convergent adaptations to cooperative breeding at the psychological and cognitive level in primates, which bear important implications for our understanding of human cognitive evolution. In the second part, we zoom in on two of these convergent adaptations, proactive prosociality and social learning, and compare their proximate regulation in marmosets and humans with regard to oxytocin and cognitive top down regulation. Our analysis suggests considerable similarity in these regulatory mechanisms presumably because the convergent traits emerged due to small motivational changes that define how pre-existing cognitive mechanisms are quantitatively combined. This finding reconciles the prima facie contradictory rationale for using marmosets as high priority model species in neuroscience and anthropology. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Brain-mapping projects using the common marmoset.

PubMed

Okano, Hideyuki; Mitra, Partha

2015-04-01

Globally, there is an increasing interest in brain-mapping projects, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative project in the USA, the Human Brain Project (HBP) in Europe, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project in Japan. These projects aim to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain. Brain/MINDS is focused on structural and functional mapping of the common marmoset (Callithrix jacchus) brain. This non-human primate has numerous advantages for brain mapping, including a well-developed frontal cortex and a compact brain size, as well as the availability of transgenic technologies. In the present review article, we discuss strategies for structural and functional mapping of the marmoset brain and the relation of the common marmoset to other animals models. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Optogenetic manipulation of neural circuits in awake marmosets

PubMed Central

MacDougall, Matthew; Nummela, Samuel U.; Coop, Shanna; Disney, Anita; Mitchell, Jude F.

2016-01-01

Optogenetics has revolutionized the study of functional neuronal circuitry (Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Nat Neurosci 8: 1263–1268, 2005; Deisseroth K. Nat Methods 8: 26–29, 2011). Although these techniques have been most successfully implemented in rodent models, they have the potential to be similarly impactful in studies of nonhuman primate brains. Common marmosets (Callithrix jacchus) have recently emerged as a candidate primate model for gene editing, providing a potentially powerful model for studies of neural circuitry and disease in primates. The application of viral transduction methods in marmosets for identifying and manipulating neuronal circuitry is a crucial step in developing this species for neuroscience research. In the present study we developed a novel, chronic method to successfully induce rapid photostimulation in individual cortical neurons transduced by adeno-associated virus to express channelrhodopsin (ChR2) in awake marmosets. We found that large proportions of neurons could be effectively photoactivated following viral transduction and that this procedure could be repeated for several months. These data suggest that techniques for viral transduction and optical manipulation of neuronal populations are suitable for marmosets and can be combined with existing behavioral preparations in the species to elucidate the functional neural circuitry underlying perceptual and cognitive processes. PMID:27334951

Adaptation and inhibition underlie responses to time-varying interaural phase cues in a model of inferior colliculus neurons.

PubMed

Borisyuk, Alla; Semple, Malcolm N; Rinzel, John

2002-10-01

A mathematical model was developed for exploring the sensitivity of low-frequency inferior colliculus (IC) neurons to interaural phase disparity (IPD). The formulation involves a firing-rate-type model that does not include spikes per se. The model IC neuron receives IPD-tuned excitatory and inhibitory inputs (viewed as the output of a collection of cells in the medial superior olive). The model cell possesses cellular properties of firing rate adaptation and postinhibitory rebound (PIR). The descriptions of these mechanisms are biophysically reasonable, but only semi-quantitative. We seek to explain within a minimal model the experimentally observed mismatch between responses to IPD stimuli delivered dynamically and those delivered statically (McAlpine et al. 2000; Spitzer and Semple 1993). The model reproduces many features of the responses to static IPD presentations, binaural beat, and partial range sweep stimuli. These features include differences in responses to a stimulus presented in static or dynamic context: sharper tuning and phase shifts in response to binaural beats, and hysteresis and "rise-from-nowhere" in response to partial range sweeps. Our results suggest that dynamic response features are due to the structure of inputs and the presence of firing rate adaptation and PIR mechanism in IC cells, but do not depend on a specific biophysical mechanism. We demonstrate how the model's various components contribute to shaping the observed phenomena. For example, adaptation, PIR, and transmission delay shape phase advances and delays in responses to binaural beats, adaptation and PIR shape hysteresis in different ranges of IPD, and tuned inhibition underlies asymmetry in dynamic tuning properties. We also suggest experiments to test our modeling predictions: in vitro simulation of the binaural beat (phase advance at low beat frequencies, its dependence on firing rate), in vivo partial range sweep experiments (dependence of the hysteresis curve on

Strength of hand preference and dual task performance by common marmosets.

PubMed

Piddington, T; Rogers, L J

2013-01-01

Study of avian and piscine species has shown that animals with stronger lateralization of the brain are able to perform two tasks presented simultaneously better than can animals with weaker lateralization. We investigated whether this might apply also to primates by testing common marmosets to see whether there is a relationship between the strength of hand preference, as an indicator of strength of brain lateralization, and the ability to carry out two tasks simultaneously. A model predator was introduced into the testing room while the marmoset was foraging. Marmosets with stronger hand preferences detected the 'predator' after shorter latency than those with weaker hand preferences. Furthermore, the marmosets with stronger hand preferences produced more mobbing (tsik) vocalizations when they reacted to the predators than did those with weaker hand preferences. There was no such association between hand preference and either latency to respond to the predator or mobbing reaction when the marmosets were not foraging at the time the predator was introduced. Hence, strength of lateralization is associated with the ability to perform foraging and predator detection simultaneously. These results are discussed with reference to the evolution of brain lateralization.

Ephrin-B2 Reverse Signaling Is Required for Topography but Not Pattern Formation of Lateral Superior Olivary Inputs to the Inferior Colliculus

PubMed Central

Wallace, Matthew M.; Kavianpour, Sarah M.; Gabriele, Mark L.

2014-01-01

Graded and modular expressions of Eph-ephrins are known to provide positional information for the formation of topographic maps and patterning in the developing nervous system. Previously we have shown that ephrin-B2 is expressed in a continuous gradient across the tonotopic axis of the central nucleus of the inferior colliculus (CNIC), whereas patterns are discontinuous and modular in the lateral cortex of the IC (LCIC). The present study explores the involvement of ephrin-B2 signaling in the development of projections to the CNIC and LCIC arising from the lateral superior olivary nuclei (LSO) prior to hearing onset. Anterograde and retrograde fluorescent tracing methods in neonatal fixed tissue preparations were used to compare topographic mapping and the establishment of LSO layers/modules in wild-type and ephrin-B2lacZ/+ mice (severely compromised reverse signaling). At birth, pioneer LSO axons occupy the ipsilateral IC in both groups but are delayed contralaterally in ephrin-B2lacZ/+ mutants. By the onset of hearing, both wild-type and mutant projections form discernible layers bilaterally in the CNIC and modular arrangements within the ipsilateral LCIC. In contrast, ephrin-B2lacZ/+ mice lack a reliable topography in LSO-IC projections, suggesting that fully functional ephrin-B2 reverse signaling is required for normal projection mapping. Taken together, these ephrin-B2 findings paired with known coexpression of EphA4 suggest the importance of these signaling proteins in establishing functional auditory circuits prior to experience. PMID:23042409

Early segregation of layered projections from the lateral superior olivary nucleusto the central nucleus of the inferior colliculus in the neonatal cat

PubMed Central

Gabriele, Mark L.; Shahmoradian, Sarah H.; French, Christopher C.; Henkel, Craig K.we; McHaffie, John G.

2007-01-01

The central nucleus of the inferior colliculus (IC) is a laminated structure that receives multiple converging afferent projections. These projections terminate in a layered arrangement and are aligned with dendritic arbors of the predominant disc-shaped neurons, forming fibrodendritic laminae. Within this structural framework, inputs terminate in a precise manner, establishing a mosaic of partially overlapping domains that likely define functional compartments. Although several of these patterned inputs have been described in the adult, relatively little is known about their organization prior to hearing onset. The present study used the lipophilic carbocyanine dyes DiI and DiD to examine the ipsilateral and contralateral projections from the lateral superior olivary (LSO) nucleus to the IC in a developmental series of paraformaldehyde-fixed kitten tissue. By birth, the crossed and uncrossed projections had reached the IC and were distributed across the frequency axis of the central nucleus. At this earliest postnatal stage, projections already exhibited a characteristic banded arrangement similar to that described in the adult. The heaviest terminal fields of the two inputs were always complementary in nature, with the ipsilateral input appearing slightly denser. This early arrangement of interdigitating ipsilateral and contralateral LSO axonal bands that occupy adjacent sublayers supports the idea that the initial establishment of this highly organized mosaic of inputs that defines distinct synaptic domains within the IC occurs largely in the absence of auditory experience. Potential developmental mechanisms that may shape these highly ordered inputs prior to hearing onset are discussed. PMID:17850770

Ephrin-B2 reverse signaling is required for topography but not pattern formation of lateral superior olivary inputs to the inferior colliculus.

PubMed

Wallace, Matthew M; Kavianpour, Sarah M; Gabriele, Mark L

2013-05-01

Graded and modular expressions of Eph-ephrins are known to provide positional information for the formation of topographic maps and patterning in the developing nervous system. Previously we have shown that ephrin-B2 is expressed in a continuous gradient across the tonotopic axis of the central nucleus of the inferior colliculus (CNIC), whereas patterns are discontinuous and modular in the lateral cortex of the IC (LCIC). The present study explores the involvement of ephrin-B2 signaling in the development of projections to the CNIC and LCIC arising from the lateral superior olivary nuclei (LSO) prior to hearing onset. Anterograde and retrograde fluorescent tracing methods in neonatal fixed tissue preparations were used to compare topographic mapping and the establishment of LSO layers/modules in wild-type and ephrin-B2(lacZ/+) mice (severely compromised reverse signaling). At birth, pioneer LSO axons occupy the ipsilateral IC in both groups but are delayed contralaterally in ephrin-B2(lacZ/+) mutants. By the onset of hearing, both wild-type and mutant projections form discernible layers bilaterally in the CNIC and modular arrangements within the ipsilateral LCIC. In contrast, ephrin-B2(lacZ/+) mice lack a reliable topography in LSO-IC projections, suggesting that fully functional ephrin-B2 reverse signaling is required for normal projection mapping. Taken together, these ephrin-B2 findings paired with known coexpression of EphA4 suggest the importance of these signaling proteins in establishing functional auditory circuits prior to experience. Copyright © 2012 Wiley Periodicals, Inc.

The dissimilar time course of temporary threshold shifts and reduction of inhibition in the inferior colliculus following intense sound exposure.

PubMed

Heeringa, A N; van Dijk, P

2014-06-01

Excessive noise exposure is known to produce an auditory threshold shift, which can be permanent or transient in nature. Recent studies showed that noise-induced temporary threshold shifts are associated with loss of synaptic connections to the inner hair cells and with cochlear nerve degeneration, which is reflected in a decreased amplitude of wave I of the auditory brainstem response (ABR). This suggests that, despite normal auditory thresholds, central auditory processing may be abnormal. We recorded changes in central auditory processing following a sound-induced temporary threshold shift. Anesthetized guinea pigs were exposed for 1 h to a pure tone of 11 kHz (124 dB sound pressure level). Hearing thresholds, amplitudes of ABR waves I and IV, and spontaneous and tone-evoked firing rates in the inferior colliculus (IC) were assessed immediately, one week, two weeks, and four weeks post exposure. Hearing thresholds were elevated immediately following overexposure, but recovered within one week. The amplitude of the ABR wave I was decreased in all sound-exposed animals for all test periods. In contrast, the ABR wave IV amplitude was only decreased immediately after overexposure and recovered within a week. The proportion of IC units that show inhibitory responses to pure tones decreased substantially up to two weeks after overexposure, especially when stimulated with high frequencies. The proportion of excitatory responses to low frequencies was increased. Spontaneous activity was unaffected by the overexposure. Despite rapid normalization of auditory thresholds, our results suggest an increased central gain following sound exposure and an abnormal balance between excitatory and inhibitory responses in the midbrain up to two weeks after overexposure. These findings may be associated with hyperacusis after a sound-induced temporary threshold shift. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Reverse audience effects on helping in cooperatively breeding marmoset monkeys.

PubMed

Brügger, R K; Kappeler-Schmalzriedt, T; Burkart, J M

2018-03-01

Cooperatively breeding common marmosets show substantial variation in the amount of help they provide. Pay-to-stay and social prestige models of helping attribute this variation to audience effects, i.e. that individuals help more if group members can witness their interactions with immatures, whereas models of kin selection, group augmentation or those stressing the need to gain parenting experience do not predict any audience effects. We quantified the readiness of adult marmosets to share food in the presence or absence of other group members. Contrary to both predictions, we found a reverse audience effect on food-sharing behaviour: marmosets would systematically share more food with immatures when no audience was present. Thus, helping in common marmosets, at least in related family groups, does not support the pay-to-stay or the social prestige model, and helpers do not take advantage of the opportunity to engage in reputation management. Rather, the results appear to reflect a genuine concern for the immatures' well-being, which seems particularly strong when solely responsible for the immatures. © 2018 The Author(s).

Age-related audiovisual interactions in the superior colliculus of the rat.

PubMed

Costa, M; Piché, M; Lepore, F; Guillemot, J-P

2016-04-21

It is well established that multisensory integration is a functional characteristic of the superior colliculus that disambiguates external stimuli and therefore reduces the reaction times toward simple audiovisual targets in space. However, in a condition where a complex audiovisual stimulus is used, such as the optical flow in the presence of modulated audio signals, little is known about the processing of the multisensory integration in the superior colliculus. Furthermore, since visual and auditory deficits constitute hallmark signs during aging, we sought to gain some insight on whether audiovisual processes in the superior colliculus are altered with age. Extracellular single-unit recordings were conducted in the superior colliculus of anesthetized Sprague-Dawley adult (10-12 months) and aged (21-22 months) rats. Looming circular concentric sinusoidal (CCS) gratings were presented alone and in the presence of sinusoidally amplitude modulated white noise. In both groups of rats, two different audiovisual response interactions were encountered in the spatial domain: superadditive, and suppressive. In contrast, additive audiovisual interactions were found only in adult rats. Hence, superior colliculus audiovisual interactions were more numerous in adult rats (38%) than in aged rats (8%). These results suggest that intersensory interactions in the superior colliculus play an essential role in space processing toward audiovisual moving objects during self-motion. Moreover, aging has a deleterious effect on complex audiovisual interactions. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of luminosity on color discrimination of dichromatic marmosets (Callithrix jacchus).

PubMed

Freitag, Fabio Batista; Pessoa, Daniel Marques Almeida

2012-02-01

Psychophysical data have shown that under mesopic conditions cones and rods can interact, improving color vision. Since electrophysiological data have suggested that rods of dichromatic marmosets appear to be active at higher luminance, we aimed to investigate the effect of different levels of sunlight on the foraging abilities of male dichromatic marmosets. Captive marmosets were observed under three different conditions, with respect to their performance in detecting colored food items against a green background. Compared to high and low light intensities, intermediate luminosities significantly increased detection of orange targets by male dichromats, an indication of rod intrusion. © 2012 Optical Society of America

A geometrically adjustable receive array for imaging marmoset cohorts.

PubMed

Gilbert, Kyle M; Gati, Joseph S; Klassen, L Martyn; Zeman, Peter; Schaeffer, David J; Everling, Stefan; Menon, Ravi S

2017-08-01

The common marmoset (Callithrix jacchus) is an increasingly popular animal model for translational neuroscience studies, during which anatomical and functional MRI can be useful investigative tools. To attain the requisite SNR for high-resolution acquisitions, the radiofrequency coil must be optimized for the marmoset; however, relatively few custom coils have been developed that maximize SNR and are compatible with accelerated acquisitions. For the study of large populations of animals, the heterogeneity in animal size reduces the effectiveness of a "one size fits all" approach to coil sizing and makes coils tailored to individual animals cost and time prohibitive. The approach taken in this study was to create an 8-channel phased-array receive coil that was adjustable to the width of the marmoset head, thereby negating the need for tailored coils while still maintaining high SNR. Two marmosets of different size were imaged on a 9.4-T small-animal scanner. Consistent SNR was achieved in the periphery of the brain between head sizes. When compared to a 15-channel, "one size fits all" receive coil, the adjustable coil achieved 57% higher SNR in the superior frontal and parietal cortices and 29% higher SNR in the centre of the brain. The mean geometry factor of the adjustable coil was less than 1.2 for a 2-fold reduction factor in the left-right and anterior-posterior directions. Geometry factors were compared to the 15-channel coil to guide future designs. The adjustable coil was shown to be a practical means for anatomical and echo-planar imaging of marmoset cohorts. Copyright © 2017 Elsevier Inc. All rights reserved.

Vocalizations associated with anxiety and fear in the common marmoset (Callithrix jacchus).

PubMed

Kato, Yoko; Gokan, Hayato; Oh-Nishi, Arata; Suhara, Tetsuya; Watanabe, Shigeru; Minamimoto, Takafumi

2014-12-15

Vocalizations of common marmoset (Callithrix jacchus) were examined under experimental situations related to fear or anxiety. When marmosets were isolated in an unfamiliar environment, they frequently vocalized "tsik-egg" calls, which were the combination calls of 'tsik' followed by several 'egg'. Tsik-egg calls were also observed after treatment with the anxiogenic drug FG-7142 (20mg/kg, sc). In contrast, when marmosets were exposed to predatory stimuli as fear-evoking situations, they frequently vocalized tsik solo calls as well as tsik-egg calls. These results suggest that marmosets dissociate the vocalization of tsik-egg and tsik calls under conditions related to fear/anxiety; tsik-egg solo vocalizations were emitted under anxiety-related conditions (e.g., isolation and anxiogenic drug treatment), whereas a mixed vocalization of tsik-egg and tsik was emitted when confronted with fear-provoking stimuli (i.e., threatening predatory stimuli). Tsik-egg call with/without tsik can be used as a specific vocal index of fear/anxiety in marmosets, which allows us to understand the neural mechanism of negative emotions in primate. Copyright © 2014 Elsevier B.V. All rights reserved.

Descending projections from the inferior colliculus to medial olivocochlear efferents: Mice with normal hearing, early onset hearing loss, and congenital deafness.

PubMed

Suthakar, Kirupa; Ryugo, David K

2017-01-01

Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea to modulate incoming acoustic signals. Two groups of efferents have been described in mouse and this report will focus on the medial olivocochlear (MOC) system. Electrophysiological data suggest the MOC efferents function in selective listening by differentially attenuating auditory nerve fiber activity in quiet and noisy conditions. Because speech understanding in noise is impaired in age-related hearing loss, we asked whether pathologic changes in input to MOC neurons from higher centers could be involved. The present study investigated the anatomical nature of descending projections from the inferior colliculus (IC) to MOCs in 3-month old mice with normal hearing, and in 6-month old mice with normal hearing (CBA/CaH), early onset progressive hearing loss (DBA/2), and congenital deafness (homozygous Shaker-2). Anterograde tracers were injected into the IC and retrograde tracers into the cochlea. Electron microscopic analysis of double-labelled tissue confirmed direct synaptic contact from the IC onto MOCs in all cohorts. These labelled terminals are indicative of excitatory neurotransmission because they contain round synaptic vesicles, exhibit asymmetric membrane specializations, and are co-labelled with antibodies against VGlut2, a glutamate transporter. 3D reconstructions of the terminal fields indicate that in normal hearing mice, descending projections from the IC are arranged tonotopically with low frequencies projecting laterally and progressively higher frequencies projecting more medially. Along the mediolateral axis, the projections of DBA/2 mice with acquired high frequency hearing loss were shifted medially towards expected higher frequency projecting regions. Shaker-2 mice with congenital deafness had a much broader spatial projection, revealing abnormalities in the topography of connections. These data suggest that loss in precision of IC directed MOC

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.

Computed Tomography of the Abdomen in Eight Clinically Normal Common Marmosets (Callithrix jacchus).

PubMed

du Plessis, W M; Groenewald, H B; Elliott, D

2017-08-01

The aim of this study was to provide a detailed anatomical description of the abdomen in the clinically normal common marmoset by means of computed tomography (CT). Eight clinically healthy mature common marmosets ranging from 12 to 48 months and 235 to 365 g bodyweight were anesthetized and pre- and post-contrast CT examinations were performed using different CT settings in dorsal recumbency. Abdominal organs were identified and visibility noted. Diagnostic quality abdominal images could be obtained of the common marmoset despite its small size using a dual-slice CT scanner. Representative cross-sectional images were chosen from different animals illustrating the abdominal CT anatomy of clinically normal common marmosets. Identification or delineation of abdominal organs greatly improved with i.v. contrast. A modified high-frequency algorithm with edge enhancement added valuable information for identification of small structures such as the ureters. The Hounsfield unit (HU) of major abdominal organs differed from that of small animals (domestic dogs and cats). Due to their size and different anatomy, standard small animal CT protocols need to be critically assessed and adapted for exotics, such as the common marmoset. The established normal reference range of HU of major abdominal organs and adapted settings for a CT protocol will aid clinical assessment of the common marmoset. © 2017 Blackwell Verlag GmbH.

Accommodation and the Visual Regulation of Refractive State in Marmosets

PubMed Central

Troilo, David; Totonelly, Kristen; Harb, Elise

2009-01-01

Purpose To determine the effects of imposed anisometropic retinal defocus on accommodation, ocular growth, and refractive state changes in marmosets. Methods Marmosets were raised with extended-wear soft contact lenses for an average duration of 10 wks beginning at an average age of 76 d. Experimental animals wore either a positive or negative contact lens over one eye and a plano lens or no lens over the other. Another group wore binocular lenses of equal magnitude but opposite sign. Untreated marmosets served as controls and three wore plano lenses monocularly. Cycloplegic refractive state, corneal curvature, and vitreous chamber depth were measured before, during, and after the period of lens wear. To investigate the accommodative response, the effective refractive state was measured through each anisometropic condition at varying accommodative stimuli positions using an infrared refractometer. Results Eye growth and refractive state are significantly correlated with the sign and power of the contact lens worn. The eyes of marmosets reared with monocular negative power lenses had longer vitreous chambers and were myopic relative to contralateral control eyes (p<0.01). Monocular positive power lenses produced a significant reduction in vitreous chamber depth and hyperopia relative to the contralateral control eyes (p<0.05). In marmosets reared binocularly with lenses of opposite sign, we found larger interocular differences in vitreous chamber depths and refractive state (p<0.001). Accommodation influences the defocus experienced through the lenses, however, the mean effective refractive state was still hyperopia in the negative-lens-treated eyes and myopia in the positive-lens-treated eyes. Conclusions Imposed anisometropia effectively alters marmoset eye growth and refractive state to compensate for the imposed defocus. The response to imposed hyperopia is larger and faster than the response to imposed myopia. The pattern of accommodation under imposed

An animal model that reflects human disease: the common marmoset (Callithrix jacchus).

PubMed

Carrion, Ricardo; Patterson, Jean L

2012-06-01

The common marmoset is a new world primate belonging to the Callitrichidae family weighing between 350 and 400 g. The marmoset has been shown to be an outstanding model for studying aging, reproduction, neuroscience, toxicology, and infectious disease. With regard to their susceptibility to infectious agents, they are exquisite NHP models for viral, protozoan and bacterial agents, as well as prions. The marmoset provides the advantages of a small animal model in high containment coupled with the immunological repertoire of a nonhuman primate and susceptibility to wild type, non-adapted viruses. Copyright © 2012 Elsevier B.V. All rights reserved.

Accommodation and convergence palsy caused by lesions in the bilateral rostral superior colliculus.

PubMed

Ohtsuka, Kenji; Maeda, Sachie; Oguri, Naomi

2002-03-01

To report a patient who developed accommodation and convergence palsy caused by lesions in the bilateral rostral superior colliculus. Observational case report. A 30-year-old right-handed man experienced sudden onset of diplopia and blurred vision at near vision. The patient showed accommodation and convergence palsy. Magnetic resonance imaging revealed lesions located in the bilateral rostral superior colliculus. These findings suggest that the rostral superior colliculus is involved in the control of accommodation and vergence eye movements.

Effect of hypoxia on the retina and superior colliculus of neonatal pigs

PubMed Central

Ruzafa, Noelia; Rey-Santano, Carmen; Mielgo, Victoria; Pereiro, Xandra; Vecino, Elena

2017-01-01

Purpose To evaluate the effect of hypoxia on the neonatal pig retina and brain, we analysed the retinal ganglion cells (RGCs) and neurons in the superior colliculus, as well as the response of astrocytes in both these central nervous system (CNS) structures. Methods Newborn pigs were exposed to 120 minutes of hypoxia, induced by decreasing the inspiratory oxygen fraction (FiO2: 10–15%), followed by a reoxygenation period of 240 minutes (FiO2: 21–35%). RGCs were quantified using Brn3a, a specific nuclear marker for these cells, and apoptosis was assessed through the appearance of active caspase-3. A morphometric analysis of the cytoskeleton of astrocytes (identified with GFAP) was performed in both the retina and superior colliculus. Results Hypoxia produced no significant change in the RGCs, although, it did induce a 37.63% increase in the number of active caspase-3 positive cells in the superior colliculus. This increase was particularly evident in the superficial layers of the superior colliculus, where 56.93% of the cells were positive for active caspase-3. In addition, hypoxia induced changes in the morphology of the astrocytes in the superior colliculus but not in the retina. Conclusions Hypoxia in the neonatal pig does not affect the retina but it does affect more central structures in the brain, increasing the number of apoptotic cells in the superior colliculus and inducing changes in astrocyte morphology. This distinct sensibility to hypoxia may pave the way to design specific approaches to combat the effects of hypoxia in specific areas of the CNS. PMID:28407001

Atypical antipsychotic clozapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of DOI into the inferior colliculus in rats.

PubMed

de Oliveira, Rodolpho Pereira; Nagaishi, Karen Yuriko; Barbosa Silva, Regina Cláudia

2017-05-15

Dysfunctions of the serotonergic system have been suggested to be important in the neurobiology of schizophrenia. Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). The hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-hydroxytryptamine(HT) 2 receptor agonist disrupted PPI in rats. The inferior colliculus (IC) is a critical nucleus of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. The present study investigated the role of serotonergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether 5-HT2A receptor activation or blockade would affect this response. Unilateral microinjection of DOI (10μg/0.3μl) into the IC disrupted PPI, while microinjection of the 5-HT2A receptor antagonist ritanserin (4μg/0.3μl), into this structure did not alter PPI. We also examined the ability of the atypical antipsychotic clozapine (5.0mg/kg; I.P.) to reverse the disruption of PPI produced by unilateral microinjections of DOI into the IC of rats. Pretreatment with clozapine blocked DOI-induced disruption of PPI. Altogether, these results suggest that serotonin-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic clozapine. Copyright © 2017 Elsevier B.V. All rights reserved.

Food Avoidance Learning in Squirrel Monkeys and Common Marmosets

PubMed Central

Laska, Matthias; Metzker, Karin

1998-01-01

Using a conditioned food avoidance learning paradigm, six squirrel monkeys (Saimiri sciureus) and six common marmosets (Callithrix jacchus) were tested for their ability to (1) reliably form associations between visual or olfactory cues of a potential food and its palatability and (2) remember such associations over prolonged periods of time. We found (1) that at the group level both species showed one-trial learning with the visual cues color and shape, whereas only the marmosets were able to do so with the olfactory cue, (2) that all individuals from both species learned to reliably avoid the unpalatable food items within 10 trials, (3) a tendency in both species for quicker acquisition of the association with the visual cues compared with the olfactory cue, (4) a tendency for quicker acquisition and higher reliability of the aversion by the marmosets compared with the squirrel monkeys, and (5) that all individuals from both species were able to reliably remember the significance of the visual cues, color and shape, even after 4 months, whereas only the marmosets showed retention of the significance of the olfactory cues for up to 4 weeks. Furthermore, the results suggest that in both species tested, illness is not a necessary prerequisite for food avoidance learning but that the presumably innate rejection responses toward highly concentrated but nontoxic bitter and sour tastants are sufficient to induce robust learning and retention. PMID:10454364

Object permanence in common marmosets (Callithrix jacchus).

PubMed

Mendes, Natacha; Huber, Ludwig

2004-03-01

A series of 9 search tasks corresponding to the Piagetian Stages 3-6 of object permanence were administered to 11 common marmosets (Callithrix jacchus). Success rates varied strongly among tasks and marmosets, but the performances of most subjects were above chance level on the majority of tasks of visible and invisible displacements. Although up to 24 trials were administered in the tests, subjects did not improve their performance across trials. Errors were due to preferences for specific locations or boxes, simple search strategies, and attentional deficits. The performances of at least 2 subjects that achieved very high scores up to the successive invisible displacement task suggest that this species is able to represent the existence and the movements of unperceived objects. ((c) 2004 APA, all rights reserved)

The neonatal marmoset monkey ovary is very primitive exhibiting many oogonia

PubMed Central

Fereydouni, B; Drummer, C; Aeckerle, N; Schlatt, S; Behr, R

2014-01-01

Oogonia are characterized by diploidy and mitotic proliferation. Human and mouse oogonia express several factors such as OCT4, which are characteristic of pluripotent cells. In human, almost all oogonia enter meiosis between weeks 9 and 22 of prenatal development or undergo mitotic arrest and subsequent elimination from the ovary. As a consequence, neonatal human ovaries generally lack oogonia. The same was found in neonatal ovaries of the rhesus monkey, a representative of the old world monkeys (Catarrhini). By contrast, proliferating oogonia were found in adult prosimians (now called Strepsirrhini), which is a group of ‘lower’ primates. The common marmoset monkey (Callithrix jacchus) belongs to the new world monkeys (Platyrrhini) and is increasingly used in reproductive biology and stem cell research. However, ovarian development in the marmoset monkey has not been widely investigated. Herein, we show that the neonatal marmoset ovary has an extremely immature histological appearance compared with the human ovary. It contains numerous oogonia expressing the pluripotency factors OCT4A, SALL4, and LIN28A (LIN28). The pluripotency factor-positive germ cells also express the proliferation marker MKI67 (Ki-67), which has previously been shown in the human ovary to be restricted to premeiotic germ cells. Together, the data demonstrate the primitiveness of the neonatal marmoset ovary compared with human. This study may introduce the marmoset monkey as a non-human primate model to experimentally study the aspects of primate primitive gonad development, follicle assembly, and germ cell biology in vivo. PMID:24840529

Head Rotation Detection in Marmoset Monkeys

NASA Astrophysics Data System (ADS)

Simhadri, Sravanthi

Head movement is known to have the benefit of improving the accuracy of sound localization for humans and animals. Marmoset is a small bodied New World monkey species and it has become an emerging model for studying the auditory functions. This thesis aims to detect the horizontal and vertical rotation of head movement in marmoset monkeys. Experiments were conducted in a sound-attenuated acoustic chamber. Head movement of marmoset monkey was studied under various auditory and visual stimulation conditions. With increasing complexity, these conditions are (1) idle, (2) sound-alone, (3) sound and visual signals, and (4) alert signal by opening and closing of the chamber door. All of these conditions were tested with either house light on or off. Infra-red camera with a frame rate of 90 Hz was used to capture of the head movement of monkeys. To assist the signal detection, two circular markers were attached to the top of monkey head. The data analysis used an image-based marker detection scheme. Images were processed using the Computation Vision Toolbox in Matlab. The markers and their positions were detected using blob detection techniques. Based on the frame-by-frame information of marker positions, the angular position, velocity and acceleration were extracted in horizontal and vertical planes. Adaptive Otsu Thresholding, Kalman filtering and bound setting for marker properties were used to overcome a number of challenges encountered during this analysis, such as finding image segmentation threshold, continuously tracking markers during large head movement, and false alarm detection. The results show that the blob detection method together with Kalman filtering yielded better performances than other image based techniques like optical flow and SURF features .The median of the maximal head turn in the horizontal plane was in the range of 20 to 70 degrees and the median of the maximal velocity in horizontal plane was in the range of a few hundreds of degrees per

Cooperative vocal control in marmoset monkeys via vocal feedback

PubMed Central

Choi, Jung Yoon; Takahashi, Daniel Y.

2015-01-01

Humans adjust speech amplitude as a function of distance from a listener; we do so in a manner that would compensate for such distance. This ability is presumed to be the product of high-level sociocognitive skills. Nonhuman primates are thought to lack such socially related flexibility in vocal production. Using predictions from a simple arousal-based model whereby vocal feedback from a conspecific modulates the drive to produce a vocalization, we tested whether another primate exhibits this type of cooperative vocal control. We conducted a playback experiment with marmoset monkeys and simulated “far-away” and “nearby” conspecifics using contact calls that differed in sound intensity. We found that marmoset monkeys increased the amplitude of their contact calls and produced such calls with shorter response latencies toward more distant conspecifics. The same was not true in response to changing levels of background noise. To account for how simulated conspecific distance can change both the amplitude and timing of vocal responses, we developed a model that incorporates dynamic interactions between the auditory system and limbic “drive” systems. Overall, our data show that, like humans, marmoset monkeys cooperatively control the acoustics of their vocalizations according to changes in listener distance, increasing the likelihood that a conspecific will hear their call. However, we propose that such cooperative vocal control is a system property that does not necessitate any particularly advanced sociocognitive skill. At least in marmosets, this vocal control can be parsimoniously explained by the regulation of arousal states across two interacting individuals via vocal feedback. PMID:25925323

Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus

PubMed Central

Akinfiresoye, Luli R.; Allard, Joanne S.; Lovinger, David M.

2015-01-01

Background: We previously reported increased current density through L-type voltage-gated Ca2+ (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown. Methods: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. Results: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. Conclusions: Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis. PMID:25556199

Duration-sensitive neurons in the inferior colliculus of horseshoe bats: adaptations for using CF-FM echolocation pulses.

PubMed

Luo, Feng; Metzner, Walter; Wu, Feijian; Wu, Feijian J; Zhang, Shuyi; Zhang, Shuyi Y; Chen, Qicai; Chen, Qicai C

2008-01-01

The present study examines duration-sensitive neurons in the inferior colliculus (IC) of the least horseshoe bat, Rhinolophus pusillus, from China. In contrast to other bat species tested for duration selectivity so far, echolocation pulses emitted by horseshoe bats are generally longer and composed of a long constant-frequency (CF) component followed by a short downward frequency-modulated (FM) sweep (CF-FM pulse). We used combined CF-FM pulses to analyze the differential effects that these two pulse components had on the duration tuning in neurons of the horseshoe bat's IC. Consistent with results from other mammals, duration-sensitive neurons found in the least horseshoe bat fall into three main classes: short-pass, band-pass, and long-pass. Using a CF stimulus alone, 54% (51/95) of all IC neurons showed at least one form of duration selectivity at one or more stimulus intensities. In 65 of the 95 IC neurons tested with CF pulses, we were also able to test their duration selectivity for a combined CF-FM pulse, which increased the ratio of duration-sensitive neurons to 66% (43/65). Seven to 15 neurons that failed to show duration tuning for CF bursts became duration sensitive for CF-FM pulses, with most of them exhibiting short-pass (depending on stimulus intensity, between 4 and 8 neurons) or band-pass tuning (1-3 neurons). Increasing stimulus intensities did not affect the duration tuning in 53% (23/43) of duration-sensitive neurons for CF bursts and in about 26% (7/27) for CF-FM stimuli. In the remaining neurons, increasing sound levels generally reduced the ratio of duration-sensitive neurons to 33% for CF and 37% for CF-FM stimulation. In those that remained duration sensitive, louder CF bursts shortened best durations in band-pass neurons and cutoff durations in short- and long-pass neurons, whereas louder CF-FM stimuli reduced the cutoff durations only in short-pass neurons. Bandwidths of band-pass neurons were not significantly affected by any stimulus

A simpler primate brain: the visual system of the marmoset monkey

PubMed Central

Solomon, Samuel G.; Rosa, Marcello G. P.

2014-01-01

Humans are diurnal primates with high visual acuity at the center of gaze. Although primates share many similarities in the organization of their visual centers with other mammals, and even other species of vertebrates, their visual pathways also show unique features, particularly with respect to the organization of the cerebral cortex. Therefore, in order to understand some aspects of human visual function, we need to study non-human primate brains. Which species is the most appropriate model? Macaque monkeys, the most widely used non-human primates, are not an optimal choice in many practical respects. For example, much of the macaque cerebral cortex is buried within sulci, and is therefore inaccessible to many imaging techniques, and the postnatal development and lifespan of macaques are prohibitively long for many studies of brain maturation, plasticity, and aging. In these and several other respects the marmoset, a small New World monkey, represents a more appropriate choice. Here we review the visual pathways of the marmoset, highlighting recent work that brings these advantages into focus, and identify where additional work needs to be done to link marmoset brain organization to that of macaques and humans. We will argue that the marmoset monkey provides a good subject for studies of a complex visual system, which will likely allow an important bridge linking experiments in animal models to humans. PMID:25152716

Comparative marker analysis after isolation and culture of testicular cells from the immature marmoset.

PubMed

Albert, Silvia; Wistuba, Joachim; Eildermann, Katja; Ehmcke, Jens; Schlatt, Stefan; Gromoll, Joerg; Kossack, Nina

2012-01-01

The marmoset monkey is a valuable model in reproductive medicine. While previous studies have evaluated germ cell dynamics in the postnatal marmoset, the features of testicular somatic cells remain largely unknown. Therefore, the aim of this study was to establish marmoset-specific markers for Sertoli and peritubular cells (PTCs) and to compare protocols for the enrichment and culture of testicular cell types. Immunohistochemistry of Sertoli and PTC-specific markers - anti-müllerian hormone (AMH), vimentin (VIM), α-smooth muscle actin (SMA) - was performed and corresponding RNA expression profiles were established by quantitative PCR analysis (SOX9,AMH, FSHR,VIM, and SMA). For these analyses, testicular tissue from newborn (n = 4), 8-week-old (n = 4) and adult (n = 3) marmoset monkeys was used. Protocols for the enrichment and culture of testicular cell fractions from the 8-week-old marmoset monkeys (n = 3) were evaluated and cells were analyzed using germ cell- and somatic cell-specific markers. The expression of AMH, VIM and SMA reflects the proportion and differentiation status of Sertoli and PTCs at the RNA and the protein levels. While applied protocols did not support the propagation of germ cells in vitro, our analyses revealed that PTCs maintain their proliferative potential and constitute the dominant cell type after short- and long-term culture. Expression of functionally meaningful testicular somatic markers is similar in the human and the marmoset monkey, indicating that this primate can indeed be used as model for human testicular development. The PTC culture system established in this study will facilitate the identification of factors influencing male sex differentiation and spermatogenesis. Copyright © 2012 S. Karger AG, Basel.

Metabolic Characterization of the Common Marmoset (Callithrix jacchus)

PubMed Central

Go, Young-Mi; Liang, Yongliang; Uppal, Karan; Soltow, Quinlyn A.; Promislow, Daniel E. L.; Wachtman, Lynn M.; Jones, Dean P.

2015-01-01

High-resolution metabolomics has created opportunity to integrate nutrition and metabolism into genetic studies to improve understanding of the diverse radiation of primate species. At present, however, there is very little information to help guide experimental design for study of wild populations. In a previous non-targeted metabolomics study of common marmosets (Callithrix jacchus), Rhesus macaques, humans, and four non-primate mammalian species, we found that essential amino acids (AA) and other central metabolites had interspecies variation similar to intraspecies variation while non-essential AA, environmental chemicals and catabolic waste products had greater interspecies variation. The present study was designed to test whether 55 plasma metabolites, including both nutritionally essential and non-essential metabolites and catabolic products, differ in concentration in common marmosets and humans. Significant differences were present for more than half of the metabolites analyzed and included AA, vitamins and central lipid metabolites, as well as for catabolic products of AA, nucleotides, energy metabolism and heme. Three environmental chemicals were present at low nanomolar concentrations but did not differ between species. Sex and age differences in marmosets were present for AA and nucleotide metabolism and warrant additional study. Overall, the results suggest that quantitative, targeted metabolomics can provide a useful complement to non-targeted metabolomics for studies of diet and environment interactions in primate evolution. PMID:26581102

Atypical antipsychotic olanzapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of dizocilpine (MK-801) into the inferior colliculus in rats.

PubMed

Zangrando, Julia; Carvalheira, Renata; Labbate, Giovanna; Medeiros, Priscila; Longo, Beatriz Monteiro; Melo-Thomas, Liana; Silva, Regina Claudia Barbosa

2013-11-15

Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviors which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. The inferior colliculus (IC) is a critical part of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. Thus, the purpose of the present study was to elucidate the role of glutamatergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether NMDA receptor stimulation or blockade would affect this response. Unilateral microinjections of NMDA (30 nmol/0.5 μL) into the IC did not alter PPI while microinjections of MK-801 (30 nmol/0.5 μL) into this structure disrupted PPI. We also examined the ability of the atypical antipsychotic olanzapine (5.0mg/kg; i.p.) to reverse the disruption of pre-pulse inhibition produced by unilateral microinjections of MK-801 into the IC of rats. Pretreatment with olanzapine blocked MK-801-induced disruption of PPI. Altogether, these results suggest that glutamate-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic olanzapine. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantification of hair cortisol concentration in common marmosets (Callithrix jacchus) and tufted capuchins (Cebus apella).

PubMed

Phillips, Kimberley A; Tukan, Alyson N; Rigodanzo, Anna D; Reusch, Ryan T; Brasky, Kathleen M; Meyer, Jerrold S

2018-06-04

Quantifying cortisol concentration in hair is a non-invasive biomarker of long-term hypothalamic-pituitary-adrenal (HPA) activation, and thus can provide important information on laboratory animal health. Marmosets (Callithrix jacchus) and capuchins (Cebus apella) are New World primates increasingly used in biomedical and neuroscience research, yet published hair cortisol concentrations for these species are limited. Review of the existing published hair cortisol values from marmosets reveals highly discrepant values and the use of variable techniques for hair collection, processing, and cortisol extraction. In this investigation we utilized a well-established, standardized protocol to extract and quantify cortisol from marmoset (n = 12) and capuchin (n = 4) hair. Shaved hair samples were collected from the upper thigh during scheduled exams and analyzed via methanol extraction and enzyme immunoassay. In marmosets, hair cortisol concentration ranged from 2,710 to 6,267 pg/mg and averaged 4,070 ± 304 pg/mg. In capuchins, hair cortisol concentration ranged from 621 to 2,089 pg/mg and averaged 1,092 ± 338 pg/mg. Hair cortisol concentration was significantly different between marmosets and capuchins, with marmosets having higher concentrations than capuchins. The incorporation of hair cortisol analysis into research protocols provides a non-invasive measure of HPA axis activity over time, which offers insight into animal health. Utilization of standard protocols across laboratories is essential to obtaining valid measurements and allowing for valuable future cross-species comparisons. © 2018 Wiley Periodicals, Inc.

Serum Albumin and Body Weight as Biomarkers for the Antemortem Identification of Bone and Gastrointestinal Disease in the Common Marmoset

PubMed Central

Baxter, Victoria K.; Shaw, Gillian C.; Sotuyo, Nathaniel P.; Carlson, Cathy S.; Olson, Erik J.; Zink, M. Christine; Mankowski, Joseph L.; Adams, Robert J.

2013-01-01

The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results. PMID:24324827

Monaural and binaural response properties of neurons in the inferior colliculus of the rabbit: effects of sodium pentobarbital.

PubMed

Kuwada, S; Batra, R; Stanford, T R

1989-02-01

1. We studied the effects of sodium pentobarbital on 22 neurons in the inferior colliculus (IC) of the rabbit. We recorded changes in the sensitivity of these neurons to monaural stimulation and to ongoing interaural time differences (ITDs). Monaural stimuli were tone bursts at or near the neuron's best frequency. The ITD was varied by delivering tones that differed by 1 Hz to the two ears, resulting in a 1-Hz binaural beat. 2. We assessed a neuron's ITD sensitivity by calculating three measures from the responses to binaural beats: composite delay, characteristic delay (CD), and characteristic phase (CP). To obtain the composite delay, we first derived period histograms by averaging, showing the response at each stimulating frequency over one period of the beat frequency. Second, the period histograms were replotted as a function of their equivalent interaural delay and then averaged together to yield the composite delay curve. Last, we calculated the composite peak or trough delay by fitting a parabola to the peak or trough of this composite curve. The composite delay curve represents the average response to all frequencies within the neuron's responsive range, and the peak reflects the interaural delay that produces the maximum response. The CD and CP were estimated from a weighted fit of a regression line to the plot of the mean interaural phase of the response versus the stimulating frequency. The slope and phase intercept of this regression line yielded estimates of CD and CP, respectively. These two quantities are thought to reflect the mechanism of ITD sensitivity, which involves the convergence of phase-locked inputs on a binaural cell. The CD estimates the difference in the time required for the two inputs to travel from either ear to this cell, whereas the CP reflects the interaural phase difference of the inputs at this cell. 3. Injections of sodium pentobarbital at subsurgical dosages (less than 25 mg/kg) almost invariably altered the neuron's response

Spermatogonial behavior in marmoset: a new generation, their kinetics and niche.

PubMed

Caldeira-Brant, A L; Eras-Garcia, L; Alves-Freitas, D; Almeida, F R C L; Chiarini-Garcia, H

2018-06-01

Could a more detailed evaluation of marmoset spermatogonial morphology, kinetics and niches using high-resolution light microscopy (HRLM) lead to new findings? Three subtypes of marmoset undifferentiated spermatogonia, which were not evenly distributed in terms of number and position along the basal membrane, and an extra premeiotic cell division not present in humans were identified using HRLM. The seminiferous epithelium cycle (SEC) of marmosets is divided into nine stages when based on the acrosome system, and several spermatogenic stages can usually be recognized within the same tubular cross-section. Three spermatogonial generations have been previously described in marmosets: types Adark, Apale and B spermatogonia. Testes from five adult Callithrix penicillata were fixed by glutaraldehyde perfusion via the cardiac route and embedded in Araldite plastic resin for HRLM evaluation. Semi-thin sections (1 μm) were analyzed morphologically and morphometrically to evaluate spermatogonial morphology and kinetics (number, mitosis and apoptosis), spermatogenesis efficiency and the spermatogonial niche. Shape and nuclear diameter, the presence and distribution of heterochromatin, the granularity of the euchromatin, as well as the number, morphology and degree of nucleolar compaction were observed for morphological characterization. Kinetics analyses were performed for all spermatogonial subtypes and preleptotene spermatocytes, and their mitosis and apoptosis indexes determined across all SEC stages. Spermatogenesis parameters (mitotic, meiotic, Sertoli cell workload and general spermatogenesis efficiency) were determined through the counting of Adark and Apale spermatogonia, preleptotene and pachytene primary spermatocytes, round spermatids, and Sertoli cells at stage IV of the SEC. This is the first time that a study in marmosets demonstrates: the existence of a new spermatogonial generation (B2); the presence of two subtypes of Adark spermatogonia with (AdVac) and

The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity.

PubMed

Riesche, Laren; Tardif, Suzette D; Ross, Corinna N; deMartelly, Victoria A; Ziegler, Toni; Rutherford, Julienne N

2018-05-01

Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.

Bioavailability and Efficacy of Levofloxacin against Francisella tularensis in the Common Marmoset (Callithrix jacchus)▿

PubMed Central

Nelson, Michelle; Lever, Mark S.; Dean, Rachel E.; Pearce, Peter C.; Stevens, Daniel J.; Simpson, Andrew J. H.

2010-01-01

Pharmacokinetic and efficacy studies with levofloxacin were performed in the common marmoset (Callithrix jacchus) model of inhalational tularemia. Plasma levofloxacin pharmacokinetics were determined in six animals in separate single-dose and multidose studies. Plasma drug concentrations were analyzed using liquid chromatography-tandem mass spectrometry-electrospray ionization. On day 7 of a twice-daily dosing regimen of 40 mg/kg, the levofloxacin half-life, maximum concentration, and area under the curve in marmoset plasma were 2.3 h, 20.9 μg/ml, and 81.4 μg/liter/h, respectively. An efficacy study was undertaken using eight treated and two untreated control animals. Marmosets were challenged with a mean of 1.5 × 102 CFU of Francisella tularensis by the airborne route. Treated animals were administered 16.5 mg/kg levofloxacin by mouth twice daily, based on the pharmacokinetic parameters, beginning 24 h after challenge. Control animals had a raised core body temperature by 57 h postchallenge and died from infection by day 5. All of the other animals survived, remained afebrile, and lacked overt clinical signs. No bacteria were recovered from the organs of these animals at postmortem after culling at day 24 postchallenge. In conclusion, postexposure prophylaxis with orally administered levofloxacin was efficacious against acute inhalational tularemia in the common marmoset. The marmoset appears to be an appropriate animal model for the evaluation of postexposure therapies. PMID:20625157

Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus

PubMed Central

Chen, Eunice C.; Liu, Maria; Brasky, Kathleen M.; Lanford, Robert E.; Kelly, Kristi R.; Bales, Karen L.; Schnurr, David P.; Canfield, Don R.; Patterson, Jean L.; Chiu, Charles Y.

2013-01-01

Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses. PMID:23894316

The behavioral context of visual displays in common marmosets (Callithrix jacchus).

PubMed

de Boer, Raïssa A; Overduin-de Vries, Anne M; Louwerse, Annet L; Sterck, Elisabeth H M

2013-11-01

Communication is important in social species, and may occur with the use of visual, olfactory or auditory signals. However, visual communication may be hampered in species that are arboreal have elaborate facial coloring and live in small groups. The common marmoset fits these criteria and may have limited visual communication. Nonetheless, some (contradictive) propositions concerning visual displays in the common marmoset have been made, yet quantitative data are lacking. The aim of this study was to assign a behavioral context to different visual displays using pre-post-event-analyses. Focal observations were conducted on 16 captive adult and sub-adult marmosets in three different family groups. Based on behavioral elements with an unambiguous meaning, four different behavioral contexts were distinguished: aggression, fear, affiliation, and play behavior. Visual displays concerned behavior that included facial expressions, body postures, and pilo-erection of the fur. Visual displays related to aggression, fear, and play/affiliation were consistent with the literature. We propose that the visual display "pilo-erection tip of tail" is related to fear. Individuals receiving these fear signals showed a higher rate of affiliative behavior. This study indicates that several visual displays may provide cues or signals of particular social contexts. Since the three displays of fear elicited an affiliative response, they may communicate a request of anxiety reduction or signal an external referent. Concluding, common marmosets, despite being arboreal and living in small groups, use several visual displays to communicate with conspecifics and their facial coloration may not hamper, but actually promote the visibility of visual displays. © 2013 Wiley Periodicals, Inc.

Early development of turn-taking with parents shapes vocal acoustics in infant marmoset monkeys

PubMed Central

Takahashi, Daniel Y.; Fenley, Alicia R.; Ghazanfar, Asif A.

2016-01-01

In humans, vocal turn-taking is a ubiquitous form of social interaction. It is a communication system that exhibits the properties of a dynamical system: two individuals become coupled to each other via acoustic exchanges and mutually affect each other. Human turn-taking develops during the first year of life. We investigated the development of vocal turn-taking in infant marmoset monkeys, a New World species whose adult vocal behaviour exhibits the same universal features of human turn-taking. We find that marmoset infants undergo the same trajectory of change for vocal turn-taking as humans, and do so during the same life-history stage. Our data show that turn-taking by marmoset infants depends on the development of self-monitoring, and that contingent parental calls elicit more mature-sounding calls from infants. As in humans, there was no evidence that parental feedback affects the rate of turn-taking maturation. We conclude that vocal turn-taking by marmoset monkeys and humans is an instance of convergent evolution, possibly as a result of pressures on both species to adopt a cooperative breeding strategy and increase volubility. PMID:27069047

Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach

PubMed Central

Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

2015-01-01

Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in

Non-viral generation of marmoset monkey iPS cells by a six-factor-in-one-vector approach.

PubMed

Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

2015-01-01

Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in

Ocular wavefront aberrations in the common marmoset Callithrix jacchus: effects of age and refractive error

PubMed Central

Coletta, Nancy J.; Marcos, Susana; Troilo, David

2012-01-01

The common marmoset, Callithrix jacchus, is a primate model for emmetropization studies. The refractive development of the marmoset eye depends on visual experience, so knowledge of the optical quality of the eye is valuable. We report on the wavefront aberrations of the marmoset eye, measured with a clinical Hartmann-Shack aberrometer (COAS, AMO Wavefront Sciences). Aberrations were measured on both eyes of 23 marmosets whose ages ranged from 18 to 452 days. Twenty-one of the subjects were members of studies of emmetropization and accommodation, and two were untreated normal subjects. Eleven of the 21 experimental subjects had worn monocular diffusers or occluders and ten had worn binocular spectacle lenses of equal power. Monocular deprivation or lens rearing began at about 45 days of age and ended at about 108 days of age. All refractions and aberration measures were performed while the eyes were cyclopleged; most aberration measures were made while subjects were awake, but some control measurements were performed under anesthesia. Wavefront error was expressed as a seventh-order Zernike polynomial expansion, using the Optical Society of America’s naming convention. Aberrations in young marmosets decreased up to about 100 days of age, after which the higher-order RMS aberration leveled off to about 0.10 micron over a 3 mm diameter pupil. Higher-order aberrations were 1.8 times greater when the subjects were under general anesthesia than when they were awake. Young marmoset eyes were characterized by negative spherical aberration. Visually deprived eyes of the monocular deprivation animals had greater wavefront aberrations than their fellow untreated eyes, particularly for asymmetric aberrations in the odd-numbered Zernike orders. Both lens-treated and deprived eyes showed similar significant increases in Z3-3 trefoil aberration, suggesting the increase in trefoil may be related to factors that do not involve visual feedback. PMID:20800078

Marmoset Cytochrome P450 3A4 Ortholog Expressed in Liver and Small-Intestine Tissues Efficiently Metabolizes Midazolam, Alprazolam, Nifedipine, and Testosterone.

PubMed

Uehara, Shotaro; Uno, Yasuhiro; Nakanishi, Kazuyuki; Ishii, Sakura; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi

2017-05-01

Common marmosets ( Callithrix jacchus ), small New World primates, are increasingly attracting attention as potentially useful animal models for drug development. However, characterization of cytochrome P450 (P450) 3A enzymes involved in the metabolism of a wide variety of drugs has not investigated in marmosets. In this study, sequence homology, tissue distribution, and enzymatic properties of marmoset P450 3A4 ortholog, 3A5 ortholog, and 3A90 were investigated. Marmoset P450 3A forms exhibited high amino acid sequence identities (88-90%) to the human and cynomolgus monkey P450 3A orthologs and evolutionary closeness to human and cynomolgus monkey P450 3A orthologs compared with other P450 3A enzymes. Among the five marmoset tissues examined, P450 3A4 ortholog mRNA was abundant in livers and small intestines where P450 3A4 ortholog proteins were immunologically detected. Three marmoset P450 3A proteins heterologously expressed in Escherichia coli membranes catalyzed midazolam 1'- and 4-hydroxylation, alprazolam 4-hydroxylation, nifedipine oxidation, and testosterone 6 β -hydroxylation, similar to cynomolgus monkey and human P450 3A enzymes. Among the marmoset P450 3A enzymes, P450 3A4 ortholog effectively catalyzed midazolam 1'-hydroxylation, comparable to microsomes from marmoset livers and small intestines. Correlation analyses with 23 individual marmoset liver microsomes suggested contributions of P450 3A enzymes to 1'-hydroxylation of both midazolam (human P450 3A probe) and bufuralol (human P450 2D6 probe), similar to cynomolgus monkey P450 3A enzymes. These results indicated that marmoset P450 3A forms had functional characteristics roughly similar to cynomolgus monkeys and humans in terms of tissue expression patterns and catalytic activities, suggesting marmosets as suitable animal models for P450 3A-dependent drug metabolism. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Use of the Common Marmoset to Study Burkholderia mallei Infection

PubMed Central

Harvey, Stephen B.; Mead, Daniel G.; Shaffer, Teresa L.; Estes, D. Mark; Michel, Frank; Quinn, Frederick D.; Hogan, Robert J.; Lafontaine, Eric R.

2015-01-01

Burkholderia mallei is a host-adapted bacterium that does not persist outside of its equine reservoir. The organism causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by B. mallei typically occurs via the respiratory or percutaneous route, and the most common manifestations are life-threatening pneumonia and bacteremia. Glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. There is no vaccine to protect against B. mallei and there is concern regarding its use as a biothreat agent. Thus, experiments were performed to establish a non-human primate model of intranasal infection to study the organism and develop countermeasures. Groups of marmosets (Callithrix jacchus) were inoculated intranasally with B. mallei strain ATCC 23344 and monitored for clinical signs of illness for up to 13 days. We discovered that 83% of marmosets inoculated with doses of 2.5 X 104 to 2.5 X 105 bacteria developed acute lethal infection within 3–4 days. Signs of disease were severe and included lethargy, inappetence, conjunctivitis, mucopurulent and hemorrhagic nasal discharges, and increased respiratory effort with abdominal lifts. Burkholderia mallei was cultured from the lungs, spleen and liver of these animals, and pathologic examination of tissues revealed lesions characteristic of glanders. Challenge experiments also revealed that 91% of animals infected with doses ranging from 25 to 2.5 X 103 bacteria exhibited mild non-specific signs of illness and were culture negative. One marmoset inoculated with 2.5 X 103 organisms developed moderate signs of disease and reached humane end-points 8 days post-infection. The liver and spleen of this animal were colonized with the agent and pathological analysis of tissues showed nasal, splenic and hepatic lesions. Taken together, these data indicate that the marmoset is a suitable model to study respiratory infection by B. mallei. PMID

Use of the common marmoset to study Burkholderia mallei infection.

PubMed

Jelesijevic, Tomislav; Zimmerman, Shawn M; Harvey, Stephen B; Mead, Daniel G; Shaffer, Teresa L; Estes, D Mark; Michel, Frank; Quinn, Frederick D; Hogan, Robert J; Lafontaine, Eric R

2015-01-01

Burkholderia mallei is a host-adapted bacterium that does not persist outside of its equine reservoir. The organism causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by B. mallei typically occurs via the respiratory or percutaneous route, and the most common manifestations are life-threatening pneumonia and bacteremia. Glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. There is no vaccine to protect against B. mallei and there is concern regarding its use as a biothreat agent. Thus, experiments were performed to establish a non-human primate model of intranasal infection to study the organism and develop countermeasures. Groups of marmosets (Callithrix jacchus) were inoculated intranasally with B. mallei strain ATCC 23344 and monitored for clinical signs of illness for up to 13 days. We discovered that 83% of marmosets inoculated with doses of 2.5 X 10(4) to 2.5 X 10(5) bacteria developed acute lethal infection within 3-4 days. Signs of disease were severe and included lethargy, inappetence, conjunctivitis, mucopurulent and hemorrhagic nasal discharges, and increased respiratory effort with abdominal lifts. Burkholderia mallei was cultured from the lungs, spleen and liver of these animals, and pathologic examination of tissues revealed lesions characteristic of glanders. Challenge experiments also revealed that 91% of animals infected with doses ranging from 25 to 2.5 X 10(3) bacteria exhibited mild non-specific signs of illness and were culture negative. One marmoset inoculated with 2.5 X 10(3) organisms developed moderate signs of disease and reached humane end-points 8 days post-infection. The liver and spleen of this animal were colonized with the agent and pathological analysis of tissues showed nasal, splenic and hepatic lesions. Taken together, these data indicate that the marmoset is a suitable model to study respiratory infection by B. mallei.

Survey and Experimental Infection of Enteropathogenic Escherichia coli in Common Marmosets (Callithrix jacchus).

PubMed

Hayashimoto, Nobuhito; Inoue, Takashi; Morita, Hanako; Yasuda, Masahiko; Ueno, Masami; Kawai, Kenji; Itoh, Toshio

2016-01-01

Common marmosets (Callithrix jacchus) are frequently used for biomedical research but can be afflicted with diarrhea-a serious and potentially lethal health problem. Enteropathogenic Escherichia coli (EPEC) is thought to be the causative pathogen of hemorrhagic typhlocolitis in common marmosets, but the actual incidence of the disease and the relationship between EPEC and hematochezia are unknown. This study investigated the prevalence of EPEC infection in common marmosets and the association between EPEC and hematochezia. A total of 230 stool or rectal swab samples were collected from 230 common marmosets (98 clinically healthy, 85 diarrhea, and 47 bloody stool samples) and tested by culture-based detection and PCR amplification of VT1, VT2, LT, ST, eae, and bfp genes. Healthy animals were divided into three groups (n = 4 each for high and low concentration groups and n = 2 as negative control), and those in the experimental groups were perorally inoculated with a 2-ml of suspension of EPEC R811 strain adjusted to 5 × 108 (high concentration) and 5 × 104 (low concentration) CFU/ ml. Two animals in each group were examined 3 and 14 days post-inoculation (DPI). EPEC was detected in 10 of 98 clinically healthy samples (10.2%), 17 of 85 diarrhea samples (20%), and all 47 bloody stool samples (100%), with a significant difference detected between presence of EPEC and sample status (P < 0.01). Acute hematochezia was observed in all animals of the high-concentration group but not in other groups at 1 or 2 DPI. A histopathological examination revealed the attachment of gram-negative bacilli to epithelial apical membranes and desquamated epithelial cells in the cecum of animals in the high-concentration group at 3 DPI. These findings suggest that EPEC is a causative agent of hemorrhagic typhlocolitis in common marmosets.

Interaural delay sensitivity and the classification of low best-frequency binaural responses in the inferior colliculus of the guinea pig.

PubMed

McAlpine, D; Jiang, D; Palmer, A R

1996-08-01

Monaural and binaural response properties of single units in the inferior colliculus (IC) of the guinea pig were investigated. Neurones were classified according to the effect of monaural stimulation of either ear alone and the effect of binaural stimulation. The majority (309/334) of IC units were excited (E) by stimulation of the contralateral ear, of which 41% (127/309) were also excited by monaural ipsilateral stimulation (EE), and the remainder (182/309) were unresponsive to monaural ipsilateral stimulation (EO). For units with best frequencies (BF) up to 3 kHz, similar proportions of EE and EO units were observed. Above 3 kHz, however, significantly more EO than EE units were observed. Units were also classified as either facilitated (F), suppressed (S), or unaffected (O) by binaural stimulation. More EO than EE units were suppressed or unaffected by binaural stimulation, and more EE than EO units were facilitated. There were more EO/S units above 1.5 kHz than below. Binaural beats were used to examine the interaural delay sensitivity of low-BF (BF < 1.5 kHz) units. The distributions of preferred interaural phases and, by extension, interaural delays, resembled those seen in other species, and those obtained using static interaural delays in the IC of the guinea pig. Units with best phase (BP) angles closer to zero generally showed binaural facilitation, whilst those with larger BPs generally showed binaural suppression. The classification of units based upon binaural stimulation with BF tones was consistent with their interaural-delay sensitivity. Characteristic delays (CD) were examined for 96 low-BF units. A clear relationship between BF and CD was observed. CDs of units with very low BFs (< 200 Hz) were long and positive, becoming progressively shorter as BF increased until, for units with BFs between 400 and 800 Hz, the majority of CDs were negative. Above 800 Hz, both positive and negative CDs were observed. A relationship between CD and characteristic

Touchscreen assays of learning, response inhibition, and motivation in the marmoset (Callithrix jacchus).

PubMed

Kangas, Brian D; Bergman, Jack; Coyle, Joseph T

2016-05-01

Recent developments in precision gene editing have led to the emergence of the marmoset as an experimental subject of considerable interest and translational value. A better understanding of behavioral phenotypes of the common marmoset will inform the extent to which forthcoming transgenic mutants are cognitively intact. Therefore, additional information regarding their learning, inhibitory control, and motivational abilities is needed. The present studies used touchscreen-based repeated acquisition and discrimination reversal tasks to examine basic dimensions of learning and response inhibition. Marmosets were trained daily to respond to one of the two simultaneously presented novel stimuli. Subjects learned to discriminate the two stimuli (acquisition) and, subsequently, with the contingencies switched (reversal). In addition, progressive ratio performance was used to measure the effort expended to obtain a highly palatable reinforcer varying in magnitude and, thereby, provide an index of relative motivational value. Results indicate that rates of both acquisition and reversal of novel discriminations increased across successive sessions, but that rate of reversal learning remained slower than acquisition learning, i.e., more trials were needed for mastery. A positive correlation was observed between progressive ratio break point and reinforcement magnitude. These results closely replicate previous findings with squirrel monkeys, thus providing evidence of similarity in learning processes across nonhuman primate species. Moreover, these data provide key information about the normative phenotype of wild-type marmosets using three relevant behavioral endpoints.

Limiting parental interaction during vocal development affects acoustic call structure in marmoset monkeys

PubMed Central

2018-01-01

Human vocal development is dependent on learning by imitation through social feedback between infants and caregivers. Recent studies have revealed that vocal development is also influenced by parental feedback in marmoset monkeys, suggesting vocal learning mechanisms in nonhuman primates. Marmoset infants that experience more contingent vocal feedback than their littermates develop vocalizations more rapidly, and infant marmosets with limited parental interaction exhibit immature vocal behavior beyond infancy. However, it is yet unclear whether direct parental interaction is an obligate requirement for proper vocal development because all monkeys in the aforementioned studies were able to produce the adult call repertoire after infancy. Using quantitative measures to compare distinct call parameters and vocal sequence structure, we show that social interaction has a direct impact not only on the maturation of the vocal behavior but also on acoustic call structures during vocal development. Monkeys with limited parental interaction during development show systematic differences in call entropy, a measure for maturity, compared with their normally raised siblings. In addition, different call types were occasionally uttered in motif-like sequences similar to those exhibited by vocal learners, such as birds and humans, in early vocal development. These results indicate that a lack of parental interaction leads to long-term disturbances in the acoustic structure of marmoset vocalizations, suggesting an imperative role for social interaction in proper primate vocal development. PMID:29651461

Limiting parental interaction during vocal development affects acoustic call structure in marmoset monkeys.

PubMed

Gultekin, Yasemin B; Hage, Steffen R

2018-04-01

Human vocal development is dependent on learning by imitation through social feedback between infants and caregivers. Recent studies have revealed that vocal development is also influenced by parental feedback in marmoset monkeys, suggesting vocal learning mechanisms in nonhuman primates. Marmoset infants that experience more contingent vocal feedback than their littermates develop vocalizations more rapidly, and infant marmosets with limited parental interaction exhibit immature vocal behavior beyond infancy. However, it is yet unclear whether direct parental interaction is an obligate requirement for proper vocal development because all monkeys in the aforementioned studies were able to produce the adult call repertoire after infancy. Using quantitative measures to compare distinct call parameters and vocal sequence structure, we show that social interaction has a direct impact not only on the maturation of the vocal behavior but also on acoustic call structures during vocal development. Monkeys with limited parental interaction during development show systematic differences in call entropy, a measure for maturity, compared with their normally raised siblings. In addition, different call types were occasionally uttered in motif-like sequences similar to those exhibited by vocal learners, such as birds and humans, in early vocal development. These results indicate that a lack of parental interaction leads to long-term disturbances in the acoustic structure of marmoset vocalizations, suggesting an imperative role for social interaction in proper primate vocal development.

Relationship between auditory thresholds, central spontaneous activity and hair cell loss after acoustic trauma

PubMed Central

Mulders, W.H.A.M.; Ding, D.; Salvi, R.; Robertson, D.

2011-01-01

Acoustic trauma caused by exposure to a very loud sound increases spontaneous activity in central auditory structures such as the inferior colliculus. This hyperactivity has been suggested as a neural substrate for tinnitus, a phantom hearing sensation. In previous studies we have described a tentative link between the frequency region of hearing impairment and the corresponding tonotopic regions in the inferior colliculus showing hyperactivity. In this study we further investigated the relationship between cochlear compound action potential threshold loss, cochlear outer and inner hair cell loss and central hyperactivity in inferior colliculus of guinea pigs. Two weeks after a 10 kHz pure tone acoustic trauma, a tight relationship was demonstrated between the frequency region of compound action potential threshold loss and frequency regions in the inferior colliculus showing hyperactivity. Extending the duration of the acoustic trauma from 1 to 2 h did not result in significant increases in final cochlear threshold loss, but did result in a further increase of spontaneous firing rates in the inferior colliculus. Interestingly, hair cell loss was not present in the frequency regions where elevated cochlear thresholds and central hyperactivity were measured, suggesting that subtle changes in hair cell or primary afferent neural function are sufficient for central hyperactivity to be triggered and maintained. PMID:21491427

Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset.

PubMed

Rodriguez-Callejas, Juan D; Fuchs, Eberhard; Perez-Cruz, Claudia

2016-01-01

Common marmosets ( Callithrix jacchus ) have recently gained popularity in biomedical research as models of aging research. Basically, they confer advantages from other non-human primates due to their shorter lifespan with onset of appearance of aging at 8 years. Old marmosets present some markers linked to neurodegeneration in the brain such as amyloid beta (Aβ) 1-42 and Aβ 1-40 . However, there are no studies exploring other cellular markers associated with neurodegenerative diseases in this non-human primate. Using immunohistochemistry, we analyzed brains of male adolescent, adult, old, and aged marmosets. We observed accumulation of Aβ 1-40 and Aβ 1-42 in the cortex of aged subjects. Tau hyperphosphorylation was already detected in the brain of adolescent animals and increased with aging in a more fibrillary form. Microglia activation was also observed in the aging process, while a dystrophic phenotype accumulates in aged subjects. Interestingly, dystrophic microglia contained hyperphosphorylated tau, but active microglia did not. These results support previous findings regarding microglia dysfunctionality in aging and neurodegenerative diseases as Alzheimer's disease. Further studies should explore the functional consequences of these findings to position this non-human primate as animal model of aging and neurodegeneration.

Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset

PubMed Central

Rodriguez-Callejas, Juan D.; Fuchs, Eberhard; Perez-Cruz, Claudia

2016-01-01

Common marmosets (Callithrix jacchus) have recently gained popularity in biomedical research as models of aging research. Basically, they confer advantages from other non-human primates due to their shorter lifespan with onset of appearance of aging at 8 years. Old marmosets present some markers linked to neurodegeneration in the brain such as amyloid beta (Aβ)1-42 and Aβ1-40. However, there are no studies exploring other cellular markers associated with neurodegenerative diseases in this non-human primate. Using immunohistochemistry, we analyzed brains of male adolescent, adult, old, and aged marmosets. We observed accumulation of Aβ1-40 and Aβ1-42 in the cortex of aged subjects. Tau hyperphosphorylation was already detected in the brain of adolescent animals and increased with aging in a more fibrillary form. Microglia activation was also observed in the aging process, while a dystrophic phenotype accumulates in aged subjects. Interestingly, dystrophic microglia contained hyperphosphorylated tau, but active microglia did not. These results support previous findings regarding microglia dysfunctionality in aging and neurodegenerative diseases as Alzheimer’s disease. Further studies should explore the functional consequences of these findings to position this non-human primate as animal model of aging and neurodegeneration. PMID:28066237

CB1 cannabinoid receptor-mediated anandamide signaling mechanisms of the inferior colliculus modulate the haloperidol-induced catalepsy.

PubMed

Medeiros, P; de Freitas, R L; Silva, M O; Coimbra, N C; Melo-Thomas, L

2016-11-19

The inferior colliculus (IC), a midbrain structure that processes acoustic information of aversive nature, is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Previous evidence relating the IC to motor behavior shows that glutamatergic and GABAergic mechanisms in the IC exert influence on systemic haloperidol-induced catalepsy. There is substantial evidence supporting a role played by the endocannabinoid system as a modulator of the glutamatergic neurotransmission, as well as the dopaminergic activity in the basal nuclei and therefore it may be considered as a potential pharmacological target for the treatment of movement disorders. The present study evaluated if the endocannabinoid system in the IC plays a role in the elaboration of systemic haloperidol-induced catalepsy. Male Wistar rats received intracollicular microinjection of either the endogenous cannabinoid anandamide (AEA) at different concentrations (5, 50 or 100pmol/0.2μl), the CB 1 cannabinoid receptor antagonist AM251 at 50, 100 or 200pmol/0.2μl or vehicle, followed by intraperitoneal (IP) administration of either haloperidol at 0.5 or 1mg/kg or physiological saline. Systemic injection of haloperidol at both doses (0.5 or 1mg/kg, IP) produced a cataleptic state, compared to vehicle/physiological saline-treated group, lasting 30 and 50min after systemic administration of the dopaminergic receptors non-selective antagonist. The midbrain microinjection of AEA at 50pmol/0.2μl increased the latency for stepping down from the horizontal bar after systemic administration of haloperidol. Moreover, the intracollicular administration of AEA at 50pmol/0.2μl was able to increase the duration of catalepsy as compared to AEA at 100pmol/0.2-μl-treated group. Intracollicular pretreatment with AM251 at the intermediate concentration (100pmol/0.2μl) was able to decrease the duration of catalepsy after systemic administration of haloperidol. However

Larger cages with housing unit environment enrichment improve the welfare of marmosets.

PubMed

Yoshimoto, Takuro; Takahashi, Eiki; Yamashita, Shunji; Ohara, Kiichi; Niimi, Kimie

2018-02-09

The provision of adequate space for laboratory animals is essential not only for good welfare but accurate studies. For example, housing conditions for primates used in biomedical research may negatively affect welfare and thus the reliability of findings. In common marmosets (Callithrix jacchus), an appropriate cage size enables a socially harmonious family environment and optimizes reproductive potential. In this study, we investigated the effects of cage size on body weight (BW), behavior, and nursing succession in the common marmoset. Large cages (LCs) with environment enrichment led to an increase in BW while small cages (SCs) caused stereotypic behaviors that were not observed in LCs. In addition, the BW of infants increased with aging in LCs. Our findings indicate that the welfare of marmosets was enhanced by living in LCs. Research on non-human primates is essential for understanding the human brain and developing knowledge-based strategies for the diagnosis and treatment of psychiatric and neurological disorders. Thus, the present findings are important because they indicate that different cages may influence emotional and behavioral phenotypes.

Molecular Cloning of Ghrelin and Characteristics of Ghrelin-Producing Cells in the Gastrointestinal Tract of the Common Marmoset (Callithrix jacchus).

PubMed

Takemi, Shota; Sakata, Ichiro; Apu, Auvijit Saha; Tsukahara, Shinji; Yahashi, Satowa; Katsuura, Goro; Iwashige, Fumihiro; Akune, Atsushi; Inui, Akio; Sakai, Takafumi

2016-10-01

Ghrelin was first isolated from human and rat as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). In the present study, we determined the ghrelin cDNA sequence of the common marmoset (Callithrix jacchus), a small-bodied New World monkey, and investigated the distribution of ghrelin-producing cells in the gastrointestinal tract and localization profiles with somatostatin-producing cells. The marmoset ghrelin cDNA coding region was 354 base pairs, and showed high homology to that in human, rhesus monkey, and mouse. Marmoset ghrelin consists of 28 amino acids, and the N-terminal region is highly conserved as found in other mammalian species. Marmoset preproghrelin and mature ghrelin have 86.3% and 92.9% homology, respectively, to their human counterparts. Quantitative RT-PCR analysis showed that marmoset ghrelin mRNA is highly expressed in the stomach, but it is not detected in other tissues of the gastrointestinal tract. In addition, a large number of ghrelin mRNA-expressing cells and ghrelin-immunopositive cells were detected in the mucosal layer of the stomach, but not in the myenteric plexus. Moreover, all the ghrelin cells examined in the stomach were observed to be closed-type. Double staining showed that somatostatin-immunopositive cells were not co-localized with ghrelin-producing cells; however, a subset of somatostatin-immunopositive cells is directly adjacent to ghrelin-immunopositive cells. These findings suggest that the distribution of ghrelin cells in marmoset differs from that in rodents, and thus the marmoset may be a more useful model for the translational study of ghrelin in primates. In conclusion, we have clarified the expression and cell distribution of ghrelin in marmoset, which may represent a useful model in translational study.

Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks.

PubMed

Ebina, Teppei; Masamizu, Yoshito; Tanaka, Yasuhiro R; Watakabe, Akiya; Hirakawa, Reiko; Hirayama, Yuka; Hira, Riichiro; Terada, Shin-Ichiro; Koketsu, Daisuke; Hikosaka, Kazuo; Mizukami, Hiroaki; Nambu, Atsushi; Sasaki, Erika; Yamamori, Tetsuo; Matsuzaki, Masanori

2018-05-14

Two-photon imaging in behaving animals has revealed neuronal activities related to behavioral and cognitive function at single-cell resolution. However, marmosets have posed a challenge due to limited success in training on motor tasks. Here we report the development of protocols to train head-fixed common marmosets to perform upper-limb movement tasks and simultaneously perform two-photon imaging. After 2-5 months of training sessions, head-fixed marmosets can control a manipulandum to move a cursor to a target on a screen. We conduct two-photon calcium imaging of layer 2/3 neurons in the motor cortex during this motor task performance, and detect task-relevant activity from multiple neurons at cellular and subcellular resolutions. In a two-target reaching task, some neurons show direction-selective activity over the training days. In a short-term force-field adaptation task, some neurons change their activity when the force field is on. Two-photon calcium imaging in behaving marmosets may become a fundamental technique for determining the spatial organization of the cortical dynamics underlying action and cognition.

Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (Callithrix jacchus).

PubMed

Uehara, Shotaro; Inoue, Takashi; Utoh, Masahiro; Toda, Akiko; Shimizu, Makiko; Uno, Yasuhiro; Sasaki, Erika; Yamazaki, Hiroshi

2016-01-01

1. Pharmacokinetics of human cytochrome P450 probes (caffeine, racemic warfarin, omeprazole, metoprolol and midazolam) composite, after single intravenous and oral administrations at doses of 0.20 and 1.0 mg kg(-1), respectively, to four male common marmosets were investigated. 2. The plasma concentrations of caffeine and warfarin decreased slowly in a monophasic manner but those of omeprazole, metoprolol and midazolam decreased extensively after intravenous and oral administrations, in a manner that approximated those as reported for pharmacokinetics in humans. 3. Bioavailabilities were ∼100% for caffeine and warfarin, but <25% for omeprazole and metoprolol. Bioavailability of midazolam was 4% in marmosets, presumably because of contribution of marmoset P450 3A4 expressed in small intestine and liver, with a high catalytic efficiency for midazolam 1'-hydroxylation as evident in the recombinant system. 4. These results suggest that common marmosets, despite their rapid clearance of some human P450 probe substrates, could be an experimental model for humans and that marmoset P450s have functional characteristics that differ from those of human and/or cynomolgus monkey P450s in some aspects, indicating their importance in modeling in P450-dependent drug metabolism studies in marmosets and of further studies.

Noise Trauma-Induced Behavioral Gap Detection Deficits Correlate with Reorganization of Excitatory and Inhibitory Local Circuits in the Inferior Colliculus and Are Prevented by Acoustic Enrichment

PubMed Central

Zhang-Hooks, Ying-Xin; Roos, Hannah

2017-01-01

Hearing loss leads to a host of cellular and synaptic changes in auditory brain areas that are thought to give rise to auditory perception deficits such as temporal processing impairments, hyperacusis, and tinnitus. However, little is known about possible changes in synaptic circuit connectivity that may underlie these hearing deficits. Here, we show that mild hearing loss as a result of brief noise exposure leads to a pronounced reorganization of local excitatory and inhibitory circuits in the mouse inferior colliculus. The exact nature of these reorganizations correlated with the presence or absence of the animals' impairments in detecting brief sound gaps, a commonly used behavioral sign for tinnitus in animal models. Mice with gap detection deficits (GDDs) showed a shift in the balance of synaptic excitation and inhibition that was present in both glutamatergic and GABAergic neurons, whereas mice without GDDs showed stable excitation–inhibition balances. Acoustic enrichment (AE) with moderate intensity, pulsed white noise immediately after noise trauma prevented both circuit reorganization and GDDs, raising the possibility of using AE immediately after cochlear damage to prevent or alleviate the emergence of central auditory processing deficits. SIGNIFICANCE STATEMENT Noise overexposure is a major cause of central auditory processing disorders, including tinnitus, yet the changes in synaptic connectivity underlying these disorders remain poorly understood. Here, we find that brief noise overexposure leads to distinct reorganizations of excitatory and inhibitory synaptic inputs onto glutamatergic and GABAergic neurons and that the nature of these reorganizations correlates with animals' impairments in detecting brief sound gaps, which is often considered a sign of tinnitus. Acoustic enrichment immediately after noise trauma prevents circuit reorganizations and gap detection deficits, highlighting the potential for using sound therapy soon after cochlear damage

Cellular Composition and Organization of the Subventricular Zone and Rostral Migratory Stream in the Adult and Neonatal Common Marmoset Brain

PubMed Central

Sawamoto, Kazunobu; Hirota, Yuki; Alfaro-Cervello, Clara; Soriano-Navarro, Mario; He, Xiaoping; Hayakawa-Yano, Yoshika; Yamada, Masayuki; Hikishima, Keigo; Tabata, Hidenori; Iwanami, Akio; Nakajima, Kazunori; Toyama, Yoshiaki; Itoh, Toshio; Alvarez-Buylla, Arturo; Garcia-Verdugo, Jose Manuel; Okano, Hideyuki

2014-01-01

The adult subventricular zone (SVZ) of the lateral ventricle contains neural stem cells. In rodents, these cells generate neuroblasts that migrate as chains toward the olfactory bulb along the rostral migratory stream (RMS). The neural-stem-cell niche at the ventricular wall is conserved in various animal species, including primates. However, it is unclear how the SVZ and RMS organization in nonhuman primates relates to that of rodents and humans. Here we studied the SVZ and RMS of the adult and neonatal common marmoset (Callithrix jacchus), a New World primate used widely in neuroscience, by electron microscopy, and immunohistochemical detection of cell-type-specific markers. The marmoset SVZ contained cells similar to type B, C, and A cells of the rodent SVZ in their marker expression and morphology. The adult marmoset SVZ had a three-layer organization, as in the human brain, with ependymal, hypocellular, and astro-cyte-ribbon layers. However, the hypocellular layer was very thin or absent in the adult-anterior and neonatal SVZ. Anti-PSA-NCAM staining of the anterior SVZ in whole-mount ventricular wall preparations of adult marmosets revealed an extensive network of elongated cell aggregates similar to the neuroblast chains in rodents. Time-lapse recordings of marmoset SVZ explants cultured in Matrigel showed the neuroblasts migrating in chains, like rodent type A cells. These results suggest that some features of neurogenesis and neuronal migration in the SVZ are common to marmosets, humans, and rodents. This basic description of the adult and neonatal marmoset SVZ will be useful for future studies on adult neurogenesis in primates. PMID:21246550

Differential modulatory effects of cocaine on marmoset monkey recognition memory.

PubMed

Melamed, Jonathan L; de Jesus, Fernando M; Aquino, Jéssica; Vannuchi, Clarissa R S; Duarte, Renata B M; Maior, Rafael S; Tomaz, Carlos; Barros, Marilia

2017-01-01

Acute and repeated exposure to cocaine alters the cognitive performance of humans and animals. How each administration schedule affects the same memory task has yet to be properly established in nonhuman primates. Therefore, we assessed the performance of marmoset monkeys in a spontaneous object-location (SOL) recognition memory task after acute and repeated exposure to cocaine (COC; 5mg/kg, ip). Two identical neutral stimuli were explored on the 10-min sample trial, after which preferential exploration of the displaced vs the stationary object was analyzed on the 10-min test trial. For the acute treatment, cocaine was given immediately after the sample presentation, and spatial recognition was then tested after a 24-h interval. For the repeated exposure schedule, daily cocaine injections were given on 7 consecutive days. After a 7-day drug-free period, the SOL task was carried out with a 10-min intertrial interval. When given acutely postsample, COC improved the marmosets' recognition memory, whereas it had a detrimental effect after the repeated exposure. Thus, depending on the administration schedule, COC exerted opposing effects on the marmosets' ability to recognize spatial changes. This agrees with recent studies in rodents and the recognition impairment seen in human addicts. Further studies related to the effects of cocaine's acute×prior drug history on the same cognitive domain are warranted. © 2017 Elsevier B.V. All rights reserved.

Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys.

PubMed

Shimizudani, Takeshi; Nagaoka, Kenjiro; Hanioka, Nobumitsu; Yamano, Shigeru; Narimatsu, Shizuo

2010-01-05

Oxidative metabolism of propranolol (PL) enantiomers (R-PL and S-PL) to 4-hydroxypropranolol (4-OH-PL), 5-OH-PL and N-deisopropylpropranolol (NDP) was examined in hepatic microsomes from cynomolgus and marmoset monkeys and in small intestinal microsomes from monkeys and humans. In hepatic microsomes, levels of oxidation activities were similar between the two monkey species, and substrate enantioselectivity (R-PLmarmosets. Inhibition experiments employing human CYP antibodies and chemical inhibitors suggested that mainly CYP2D enzymes and partially CYP1A and 2C enzymes are involved in the oxidation of PL in both monkey liver microsomes. In small intestinal microsomes, activity levels were much higher in cynomolgus monkeys than in marmosets and humans and reversed substrate enantioselectivity (R-PL>S-PL) was seen in the formation of NDP in cynomolgus monkeys and humans and in the formation of 5-OH-PL in marmosets. The formation of the three metabolites in cynomolgus monkeys and the formation of NDP in marmosets were biphasic, while the formation of 4-OH-PL in humans was monophasic. From the inhibition experiments using CYP antibodies, CYP2C9 and 2C19 were thought to be involved as N-deisopropylases and CYP2D6 and 3A4 as 4-hydroxylases in human small intestine. Furthermore, CYP1A, 2C and 3A enzymes could be involved in cynomolgus monkeys and CYP2C and 3A enzymes in marmosets. These results indicate that the oxidative profile of PL in hepatic and small intestinal microsomes differ considerably among cynomolgus monkeys, marmosets and humans.

Social Context-Dependent Activity in Marmoset Frontal Cortex Populations during Natural Conversations

PubMed Central

de la Mothe, Lisa; Miller, Cory T.

2017-01-01

Communication is an inherently interactive process that weaves together the fabric of both human and nonhuman primate societies. To investigate the properties of the primate brain during active social signaling, we recorded the responses of frontal cortex neurons as freely moving marmosets engaged in conversational exchanges with a visually occluded virtual marmoset. We found that small changes in firing rate (∼1 Hz) occurred across a broadly distributed population of frontal cortex neurons when marmosets heard a conspecific vocalization, and that these changes corresponded to subjects' likelihood of producing or withholding a vocal reply. Although the contributions of individual neurons were relatively small, large populations of neurons were able to clearly distinguish between these social contexts. Most significantly, this social context-dependent change in firing rate was evident even before subjects heard the vocalization, indicating that the probability of a conversational exchange was determined by the state of the frontal cortex at the time a vocalization was heard, and not by a decision driven by acoustic characteristics of the vocalization. We found that changes in neural activity scaled with the length of the conversation, with greater changes in firing rate evident for longer conversations. These data reveal specific and important facets of this neural activity that constrain its possible roles in active social signaling, and we hypothesize that the close coupling between frontal cortex activity and this natural, active primate social-signaling behavior facilitates social-monitoring mechanisms critical to conversational exchanges. SIGNIFICANCE STATEMENT We provide evidence for a novel pattern of neural activity in the frontal cortex of freely moving, naturally behaving, marmoset monkeys that may facilitate natural primate conversations. We discovered small (∼1 Hz), but reliable, changes in neural activity that occurred before marmosets even heard a

Oocyte-activating capacity of fresh and frozen-thawed spermatids in the common marmoset (Callithrix jacchus).

PubMed

Ogonuki, Narumi; Inoue, Hiroki; Matoba, Shogo; Kurotaki, Yoko K; Kassai, Hidetoshi; Abe, Yukiko; Sasaki, Erika; Aiba, Atsu; Ogura, Atsuo

2018-02-19

The common marmoset (Callithrix jacchus) represents a promising nonhuman primate model for the study of human diseases because of its small size, ease of handling, and availability of gene-modified animals. Here, we aimed to devise reproductive technology for marmoset spermatid injection using immature males for a possible rapid generational turnover. Spermatids at each step could be identified easily by their morphology under differential interference microscopy: thus, early round spermatids had a round nucleus with a few nucleolus-like structures and abundant cytoplasm, as in other mammals. The spermatids acquired oocyte-activating capacity at the late round spermatid stage, as confirmed by the resumption of meiosis and Ca 2+ oscillations upon injection into mouse oocytes. The spermatids could be cryopreserved efficiently with a simple medium containing glycerol and CELL BANKER®. Late round or elongated spermatids first appeared at 10-12 months of age, 6-8 months before sexual maturation. Marmoset oocytes microinjected with frozen-thawed late round or elongated spermatids retrieved from a 12-month-old male marmoset developed to the 8-cell stage without the need for artificial oocyte activation stimulation. Thus, it might be possible to shorten the intergeneration time by spermatid injection, from 2 years (by natural mating) to 13-15 months including gestation. © 2018 Wiley Periodicals, Inc.

THE SUSCEPTIBILITY OF MARMOSETS TO YELLOW FEVER VIRUS

PubMed Central

Davis, Nelson C.

1930-01-01

1. It has been possible to introduce yellow fever virus into the small Brazilian monkeys, Callithrix albicollis and Leontocebus ursulus, by the bites of infected mosquitoes and to carry the virus through a series of four passages in each species and back to rhesus monkeys by the bites of Stegomyia mosquitoes fed on the last marmoset of each series. 2. Five specimens of L. ursulus were used. Four developed fever, and all died during the experiments. At least two showed liver necroses comparable to those found in human beings and rhesus monkeys that died of yellow fever. 3. Twenty specimens of C. albicollis were used. Very few showed a temperature reaction following the introduction of virus. Of those that died, none had lesions typical of yellow fever as seen in certain other species of monkeys and in humans. 4. The convalescent serum from each of five C. albicollis protected a rhesus monkey against yellow fever virus, but the serum from a normal marmoset of the same species was found to be non-protective. PMID:19869773

Colonization of collagen scaffolds by adipocytes derived from mesenchymal stem cells of the common marmoset monkey

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

Bernemann, Inga, E-mail: bernemann@imp.uni-hannover.de; Mueller, Thomas; Blasczyk, Rainer

Highlights: {yields} Marmoset bone marrow-derived MSCs differentiate in suspension into adipogenic, osteogenic and chondrogenic lineages. {yields} Marmoset MSCs integrate in collagen type I scaffolds and differentiate excellently into adipogenic cells. {yields} Common marmoset monkey is a suitable model for soft tissue engineering in human regenerative medicine. -- Abstract: In regenerative medicine, human cell replacement therapy offers great potential, especially by cell types differentiated from immunologically and ethically unproblematic mesenchymal stem cells (MSCs). In terms of an appropriate carrier material, collagen scaffolds with homogeneous pore size of 65 {mu}m were optimal for cell seeding and cultivating. However, before clinical application andmore » transplantation of MSC-derived cells in scaffolds, the safety and efficiency, but also possible interference in differentiation due to the material must be preclinically tested. The common marmoset monkey (Callithrix jacchus) is a preferable non-human primate animal model for this aim due to its genetic and physiological similarities to the human. Marmoset bone marrow-derived MSCs were successfully isolated, cultured and differentiated in suspension into adipogenic, osteogenic and chondrogenic lineages by defined factors. The differentiation capability could be determined by FACS. Specific marker genes for all three cell types could be detected by RT-PCR. Furthermore, MSCs seeded on collagen I scaffolds differentiated in adipogenic lineage showed after 28 days of differentiation high cell viability and homogenous distribution on the material which was validated by calcein AM and EthD staining. As proof of adipogenic cells, the intracellular lipid vesicles in the cells were stained with Oil Red O. The generation of fat vacuoles was visibly extensive distinguishable and furthermore determined on the molecular level by expression of specific marker genes. The results of the study proved both the

Corticospinal Tract Tracing in the Marmoset with a Clinical Whole-Body 3T Scanner Using Manganese-Enhanced MRI

PubMed Central

Plas, Benjamin; Bolan, Faye; Boulanouar, Kader; Renaud, Luc; Darmana, Robert; Vaysse, Laurence; Vieu, Christophe; Loubinoux, Isabelle

2015-01-01

Manganese-enhanced MRI (MEMRI) has been described as a powerful tool to depict the architecture of neuronal circuits. In this study we investigated the potential use of in vivo MRI detection of manganese for tracing neuronal projections from the primary motor cortex (M1) in healthy marmosets (Callithrix Jacchus). We determined the optimal dose of manganese chloride (MnCl2) among 800, 400, 40 and 8nmol that led to manganese-induced hyperintensity furthest from the injection site, as specific to the corticospinal tract as possible, and that would not induce motor deficit. A commonly available 3T human clinical MRI scanner and human knee coil were used to follow hyperintensity in the corticospinal tract 24h after injection. A statistical parametric map of seven marmosets injected with the chosen dose, 8 nmol, showed the corticospinal tract and M1 connectivity with the basal ganglia, substantia nigra and thalamus. Safety was determined for the lowest dose that did not induce dexterity and grip strength deficit, and no behavioral effects could be seen in marmosets who received multiple injections of manganese one month apart. In conclusion, our study shows for the first time in marmosets, a reliable and reproducible way to perform longitudinal ME-MRI experiments to observe the integrity of the marmoset corticospinal tract on a clinical 3T MRI scanner. PMID:26398500

Regio- and Stereo-Selective Oxidation of a Cardiovascular Drug, Metoprolol, Mediated by Cytochrome P450 2D and 3A Enzymes in Marmoset Livers.

PubMed

Uehara, Shotaro; Ishii, Sakura; Uno, Yasuhiro; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi

2017-08-01

A β -blocker, metoprolol, is one of the in vivo probes for human cytochrome P450 (P450) 2D6. Investigation of nonhuman primate P450 enzymes helps to improve the accuracy of the extrapolation of pharmacokinetic data from animals into humans. Common marmosets ( Callithrix jacchus ) are a potential primate model for preclinical research, but the detailed roles of marmoset P450 enzymes in metoprolol oxidation remain unknown. In this study, regio- and stereo-selectivity of metoprolol oxidations by a variety of P450 enzymes in marmoset and human livers were investigated in vitro. Although liver microsomes from cynomolgus monkeys and rats preferentially mediated S -metoprolol O -demethylation and R -metoprolol α -hydroxylation, respectively, those from humans, marmosets, minipigs, and dogs preferentially mediated R -metoprolol O -demethylation, in contrast to the slow rates of R - and S -metoprolol oxidation in mouse liver microsomes. R - and S -metoprolol O -demethylation activities in marmoset livers were strongly inhibited by quinidine and ketoconazole, and were significantly correlated with bufuralol 1'-hydroxylation and midazolam 1'-hydroxylation activities and also with P450 2D and 3A4 contents, which is different from the case in human livers that did not have any correlations with P450 3A-mediated midazolam 1'-hydroxylation. Recombinant human P450 2D6 enzyme and marmoset P450 2D6/3A4 enzymes effectively catalyzed R -metoprolol O -demethylation, comparable to the activities of human and marmoset liver microsomes, respectively. These results indicated that the major roles of P450 2D enzymes for the regio- and stereo-selectivity of metoprolol oxidation were similar between human and marmoset livers, but the minor roles of P450 3A enzymes were unique to marmosets. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Fatal attack on black-tufted-ear marmosets (Callithrix penicillata) by a Boa constrictor: a simultaneous assault on two juvenile monkeys.

PubMed

Teixeira, Danilo Simonini; dos Santos, Edmilson; Leal, Silvana Gomes; de Jesus, Andrea Karla; Vargas, Waldemir Paixão; Dutra, Irapuan; Barros, Marilia

2016-01-01

Here we report the first witnessed attack on a marmoset by a constrictor snake. The incident occurred mid-morning in a gallery forest within an altered landscape of the Cerrado region of central Brazil and refers to a fatal attack by a Boa constrictor on two juvenile black-tufted-ear marmosets (Callithrix penicillata) simultaneously. The snake captured both individuals at a height of ~ 4 m while a group of eight marmosets traveled through the subcanopy. The actual strike was not seen. After 2 min, the boa fell to the ground with both marmosets in its coils and proceeded to kill one animal at a time through constriction. Two adult marmosets immediately descended to where the snake held its victims on the ground and attacked it. The snake showed no apparent reaction, and after ~ 1-2 min, the adults rejoined the remaining group members that were mobbing and vocalizing from 5 to 6 m above. The group left the scene ~ 7 min after the onset of the attack and was not seen again. The snake loosened its coils 10 min after its initial strike, left the two carcasses on the ground and stayed behind a nearby tree. Thus, we are not sure if the victims were in fact ingested. This report confirms that marmosets are vulnerable to boid snakes and capable of highly organized and cooperative antipredation behavior. It also suggests that snakes pose a greater threat to callitrichids than previously thought.

Bisphenol A-induced ultrastructural changes in the testes of common marmoset

PubMed Central

Vijaykumar, Tushara; Singh, Dipty; Vanage, Geeta R.; Dhumal, Rohit V.; Dighe, Vikas D.

2017-01-01

Background & objectives: Bisphenol A (BPA) is an endocrine disruptor that is widely used in the manufacture of polycarbonate plastics, epoxy resins and dental sealants. It is known to have adverse effects on spermatogenesis in rodents. This study was aimed to evaluate the effects of BPA in adult common marmoset owing to its similarities with human spermatogenesis. Methods: Sixteen marmosets were divided into four groups (n=4 per group) and given oral doses of BPA (2.5, 12.5 and 25 μg/kg BW/day) for 70 days to cover two spermatogenic cycles, and the control group received only vehicle (honey). Testes were processed for histological and transmission electron microscopy studies. Results: Histology of the testis showed sloughing of germ cells into the lumen, increase in interstitial space and vacuolation of Sertoli cell cytoplasm. Ultrastructural analysis of the testis revealed several degenerative effects on the basement membrane, Sertoli cells, Leydig cells and other developing germ cells in the 12.5 and 25 μg/kg BW/day groups as compared to control. Interpretation & conclusions: The observed ultrastructural changes caused by BPA in testicular morphology might be indicative of a perturbed sperm production. Considering the genetic and spermatogenic similarities of common marmoset (Callithrix jacchus) and humans, the study findings are of significance. Further studies are, however, needed to elucidate the mechanism of action. PMID:29168469

Bisphenol A-induced ultrastructural changes in the testes of common marmoset.

PubMed

Vijaykumar, Tushara; Singh, Dipty; Vanage, Geeta R; Dhumal, Rohit V; Dighe, Vikas D

2017-07-01

Bisphenol A (BPA) is an endocrine disruptor that is widely used in the manufacture of polycarbonate plastics, epoxy resins and dental sealants. It is known to have adverse effects on spermatogenesis in rodents. This study was aimed to evaluate the effects of BPA in adult common marmoset owing to its similarities with human spermatogenesis. Sixteen marmosets were divided into four groups (n=4 per group) and given oral doses of BPA (2.5, 12.5 and 25 μg/kg BW/day) for 70 days to cover two spermatogenic cycles, and the control group received only vehicle (honey). Testes were processed for histological and transmission electron microscopy studies. Histology of the testis showed sloughing of germ cells into the lumen, increase in interstitial space and vacuolation of Sertoli cell cytoplasm. Ultrastructural analysis of the testis revealed several degenerative effects on the basement membrane, Sertoli cells, Leydig cells and other developing germ cells in the 12.5 and 25 μg/kg BW/day groups as compared to control. The observed ultrastructural changes caused by BPA in testicular morphology might be indicative of a perturbed sperm production. Considering the genetic and spermatogenic similarities of common marmoset (Callithrix jacchus) and humans, the study findings are of significance. Further studies are, however, needed to elucidate the mechanism of action.

A combined histological and MRI brain atlas of the common marmoset monkey, Callithrix jacchus.

PubMed

Newman, John D; Kenkel, William M; Aronoff, Emily C; Bock, Nicholas A; Zametkin, Molly R; Silva, Afonso C

2009-12-11

The common marmoset, Callithrix jacchus, is of growing importance for research in neuroscience and related fields. In the present work, we describe a combined histological and magnetic resonance imaging (MRI) atlas constructed from the brains of two adult female marmosets. Histological sections were processed from Nissl staining and digitized to produce an atlas in a large format that facilitates visualization of structures with significant detail. Naming of identifiable brain structures was performed utilizing current terminology. The histological sections and a simplified schematic atlas are available online at http://udn.nichd.nih.gov/brainatlas_home.html.

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.

Isolation and characterization of a novel Helicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus)

PubMed Central

Shen, Zeli; Feng, Yan; Sheh, Alexander; Everitt, Jeffrey; Bertram, Frederick; Paster, Bruce J.

2015-01-01

Purpose-bred common marmosets from domestic sources housed in a US research facility, and used in multiple drug discovery programmes, were noted to have a high incidence of spontaneous inflammatory bowel disease and sporadic cholecystitis and cholangiohepatitis. Inflammatory infiltrates increased in incidence and severity with age. Because Helicobacter spp. have been linked to gastrointestinal diseases, samples from the gastrointestinal tracts of 39 marmosets were screened for Helicobacter spp. by culture and PCR. Helicobacter spp. were frequently detected in marmosets; 28.2 % of the marmosets were positive for a proposed novel species, Helicobacter jaachi sp. nov., by culture, and 48.7 % were positive by Helicobacter genus-specific PCR. Seventeen strains of Helicobacter sp. from 11 marmosets were cultured from various gastrointestinal sites. Older animals (age 6–11 years) had a higher helicobacter prevalence rate (57.1 %) compared with younger animals (age 3–5 years), which had a 27.2 % prevalence rate. Cells of H. jaachi sp. nov. were catalase, urease and oxidase positive and had fusiform morphology, with periplasmic fibres and multiple bipolar, sheathed flagella. All isolates had similar 16S and 23S rRNA sequences, which clustered as representatives of a novel Helicobacter species closely related to ‘Helicobacter sanguini’ (97 %), a species isolated from cotton-top tamarins and ‘Helicobacter callitrichis’ (96 %) isolated previously from the faeces of common marmosets. The whole genome sequence of one of the liver isolates, H. jaachi sp. nov. MIT 09-6949T, had a 1.9 Mb genome length with a 41 mol% DNA G+C content. The type strain of Helicobacter jaachi sp. nov., MIT 09-6949T, has been deposited in the BCCM/LMG Bacteria Collection as LMG 28613T. These findings add to the increasing number of animal species with gastrointestinal disease in which novel enterohepatic Helicobacter spp. have been isolated. PMID:26297446

The development of a specific pathogen free (SPF) barrier colony of marmosets (Callithrix jacchus) for aging research

PubMed Central

Ross, Corinna N.; Austad, Steven; Brasky, Kathy; Brown, Celeste J.; Forney, Larry J.; Gelfond, Jonathan A.; Lanford, Robert; Richardson, Arlan; Tardif, Suzette D.

2017-01-01

A specific pathogen free (SPF) barrier colony of breeding marmosets (Callithrix jacchus) was established at the Barshop Institute for Longevity and Aging Studies. Rodent and other animal models maintained as SPF barrier colonies have demonstrated improved health and lengthened lifespans enhancing the quality and repeatability of aging research. The marmosets were screened for two viruses and several bacterial pathogens prior to establishing the new SPF colony. Twelve founding animals successfully established a breeding colony with increased reproductive success, improved health parameters, and increased median lifespan when compared to a conventionally housed, open colony. The improved health and longevity of marmosets from the SPF barrier colony suggests that such management can be used to produce a unique resource for future studies of aging processes in a nonhuman primate model. PMID:29227963

A digital 3D atlas of the marmoset brain based on multi-modal MRI.

PubMed

Liu, Cirong; Ye, Frank Q; Yen, Cecil Chern-Chyi; Newman, John D; Glen, Daniel; Leopold, David A; Silva, Afonso C

2018-04-01

The common marmoset (Callithrix jacchus) is a New-World monkey of growing interest in neuroscience. Magnetic resonance imaging (MRI) is an essential tool to unveil the anatomical and functional organization of the marmoset brain. To facilitate identification of regions of interest, it is desirable to register MR images to an atlas of the brain. However, currently available atlases of the marmoset brain are mainly based on 2D histological data, which are difficult to apply to 3D imaging techniques. Here, we constructed a 3D digital atlas based on high-resolution ex-vivo MRI images, including magnetization transfer ratio (a T1-like contrast), T2w images, and multi-shell diffusion MRI. Based on the multi-modal MRI images, we manually delineated 54 cortical areas and 16 subcortical regions on one hemisphere of the brain (the core version). The 54 cortical areas were merged into 13 larger cortical regions according to their locations to yield a coarse version of the atlas, and also parcellated into 106 sub-regions using a connectivity-based parcellation method to produce a refined atlas. Finally, we compared the new atlas set with existing histology atlases and demonstrated its applications in connectome studies, and in resting state and stimulus-based fMRI. The atlas set has been integrated into the widely-distributed neuroimaging data analysis software AFNI and SUMA, providing a readily usable multi-modal template space with multi-level anatomical labels (including labels from the Paxinos atlas) that can facilitate various neuroimaging studies of marmosets. Published by Elsevier Inc.

Vasopressin and Oxytocin Reduce Food Sharing Behavior in Male, but Not Female Marmosets in Family Groups

PubMed Central

Taylor, Jack H.; Intorre, Allison A.; French, Jeffrey A.

2017-01-01

Oxytocin (OT) is critical for lactation and maternal care, but OT and the related nonapeptide vasopressin are important for caregiving behaviors in fathers and alloparents as well. This experiment tested the effects of vasopressin and OT on food sharing in marmoset families. We treated caregivers (parents, siblings) with intranasal vasopressin, OT, or saline, and then paired them with the youngest marmoset in the family. Caregivers were given preferred food, and then observed for food sharing and aggressive behavior with young marmosets. OT reduced food sharing from male alloparents to youngest siblings, and fathers that received vasopressin refused to share food with their youngest offspring more often than when treated with OT. Vasopressin increased aggressive vocalizations directed toward potential food recipients in all classes of caregivers. These results indicate that vasopressin and OT do not always enhance prosocial behavior: modulation of food sharing depends on both sex and parental status. PMID:28798724

Vasopressin and Oxytocin Reduce Food Sharing Behavior in Male, but Not Female Marmosets in Family Groups.

PubMed

Taylor, Jack H; Intorre, Allison A; French, Jeffrey A

2017-01-01

Oxytocin (OT) is critical for lactation and maternal care, but OT and the related nonapeptide vasopressin are important for caregiving behaviors in fathers and alloparents as well. This experiment tested the effects of vasopressin and OT on food sharing in marmoset families. We treated caregivers (parents, siblings) with intranasal vasopressin, OT, or saline, and then paired them with the youngest marmoset in the family. Caregivers were given preferred food, and then observed for food sharing and aggressive behavior with young marmosets. OT reduced food sharing from male alloparents to youngest siblings, and fathers that received vasopressin refused to share food with their youngest offspring more often than when treated with OT. Vasopressin increased aggressive vocalizations directed toward potential food recipients in all classes of caregivers. These results indicate that vasopressin and OT do not always enhance prosocial behavior: modulation of food sharing depends on both sex and parental status.

Stereo Navi 2.0: software for stereotaxic surgery of the common marmoset (Callithrix jacchus).

PubMed

Tokuno, Hironobu; Tanaka, Ikuko; Umitsu, Yoshitomo; Nakamura, Yasuhisa

2009-11-01

Recently, we reported our web-accessible digital brain atlas of the common marmoset (Callithrix jacchus) at http://marmoset-brain.org:2008. Using digital images obtained during construction of this website, we developed stand-alone software for navigation of electrodes or injection needles for stereotaxic electrophysiological or anatomical experiments in vivo. This software enables us to draw lines on exchangeable section images, measure the length and angle of lines, superimpose a stereotaxic reference grid on the image, and send the image to the system clipboard. The software, Stereo Navi 2.0, is freely available at our brain atlas website.

Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

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

Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov; Via, Laura E.; Kumar, Mia R.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT),more » with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.« less

The Brain/MINDS 3D digital marmoset brain atlas

PubMed Central

Woodward, Alexander; Hashikawa, Tsutomu; Maeda, Masahide; Kaneko, Takaaki; Hikishima, Keigo; Iriki, Atsushi; Okano, Hideyuki; Yamaguchi, Yoko

2018-01-01

We present a new 3D digital brain atlas of the non-human primate, common marmoset monkey (Callithrix jacchus), with MRI and coregistered Nissl histology data. To the best of our knowledge this is the first comprehensive digital 3D brain atlas of the common marmoset having normalized multi-modal data, cortical and sub-cortical segmentation, and in a common file format (NIfTI). The atlas can be registered to new data, is useful for connectomics, functional studies, simulation and as a reference. The atlas was based on previously published work but we provide several critical improvements to make this release valuable for researchers. Nissl histology images were processed to remove illumination and shape artifacts and then normalized to the MRI data. Brain region segmentation is provided for both hemispheres. The data is in the NIfTI format making it easy to integrate into neuroscience pipelines, whereas the previous atlas was in an inaccessible file format. We also provide cortical, mid-cortical and white matter boundary segmentations useful for visualization and analysis. PMID:29437168

Expression of tumor necrosis factor-α and interleukin-1β genes in the cochlea and inferior colliculus in salicylate-induced tinnitus

PubMed Central

2011-01-01

Background Changes in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate. Methods Forty-eight 3-month-old male SAMP8 mice were randomly and equally divided into two groups: salicylate-treated and saline-treated. All mice were trained to perform an active avoidance task for 5 days. Once conditioned, an active avoidance task was performed 2 hours after daily intraperitoneal injections of saline, either alone or containing 300 mg/kg sodium salicylate. Total numbers of times (tinnitus score) the mice climbed during the inter-trial silent period for 10 trials were recorded daily for 4 days (days 7 to 10), and then mice were euthanized for determination of mRNA expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC at day 10. Results Tinnitus scores increased in response to daily salicylate treatments. The mRNA expression levels of TNF-α increased significantly for the salicylate-treated group compared to the control group in both cochlea (1.89 ± 0.22 vs. 0.87 ± 0.07, P < 0.0001) and IC (2.12 ± 0.23 vs. 1.73 ± 0.22, p = 0.0040). mRNA expression levels for the IL-1β gene also increased significantly in the salicylate group compared to the control group in both cochlea (3.50 ± 1.05 vs. 2.80 ± 0.28, p < 0.0001) and IC (2.94 ± 0.51 versus 1.24 ± 0.52, p = 0.0013). Linear regression analysis revealed a significant positive association between tinnitus scores and expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC. In addition, expression levels of the TNF-α gene were positively correlated with those of the NR2Bgene in both cochlea and IC; whereas, the expression levels of the IL-1β gene was positively correlated with that of

An Observational Investigation of Behavioral Contagion in Common Marmosets (Callithrix jacchus): Indications for Contagious Scent-Marking

PubMed Central

Massen, Jorg J. M.; Šlipogor, Vedrana; Gallup, Andrew C.

2016-01-01

Behavioral contagion is suggested to promote group coordination that may facilitate activity transitions, increased vigilance, and state matching. Apart from contagious yawning, however, very little attention has been given to this phenomenon, and studies on contagious yawning in primates have so far only focused on Old World monkeys and apes. Here we studied behavioral contagion in common marmosets, a species for which group coordination and vigilance are paramount. In particular, we investigated the contagiousness of yawning, stretching, scratching, tongue protrusion, gnawing, and scent-marking. We coded these behaviors from 14 adult marmosets, from two different social groups. During testing sessions, animals were separated into groups of four individuals for 20-min observation periods, across three distinct diurnal time points (morning, midday, and afternoon) to test for circadian patterns. We observed almost no yawning (0.12 yawns/h) and very little stretching behavior. For all other behaviors, which were more common, we found several temporal and inter-individual differences (i.e., sex, age, dominance status) predictive of these responses. Moreover, we found that gnawing and scent-marking, which almost always co-occurred as a fixed-action pattern, were highly temporally clustered within observation sessions. We discuss the relative absence of yawning in marmosets as well as the possible function of contagious scent-marking, and provide suggestions for future research into the proximate and ultimate functions of these behaviors in marmosets. PMID:27563294

Immediate, but no delayed, behavioral response to a snake model by captive black tufted-ear marmosets.

PubMed

Cagni, Priscila; Sampaio, Ana Cristhina; Ribeiro, Natália B; Barros, Marilia

2011-07-01

Whether callitrichids are naturally capable of detecting and responding to predators - or if such skills are learned - remains a controversial issue, with results differing in terms of species, predator and encounter conditions. Therefore, the behavioral response of naïve adult captive black tufted-ear marmosets (Callithrix penicillata) was assessed before, during, 0 and 4 h after a 5-min encounter with a snake and flower model. Using a two-phase cross-over design, marmosets (n = 16) were submitted to one trial for each stimulus, divided into four 5-min intervals: pre-exposure, exposure and post-exposure observations held 0 and 4h later. The snake exposure increased the number of gazes made towards the stimulus and the time cage-mates spent close to each other, as well as induced tsik-tsik alarm/mobbing calls, while inhibiting foraging and decreasing the time spent near the snake's location. After the snake was removed, all changes were immediately reversed. Mobbing was not observed. The flower stimulus only increased direct gazes and time spent in proximity during its presentation. All marmosets were captive-born and snake-naïve yet had recently been confronted with a cat stimulus in a previous experiment. Thus, previous experiences with snakes may be required for marmosets to fully develop appropriate immediate and long-term responses. Copyright © 2011 Elsevier B.V. All rights reserved.

Birth of Healthy Offspring following ICSI in In Vitro-Matured Common Marmoset (Callithrix jacchus) Oocytes

PubMed Central

Takahashi, Tsukasa; Hanazawa, Kisaburo; Inoue, Takashi; Sato, Kenya; Sedohara, Ayako; Okahara, Junko; Suemizu, Hiroshi; Yagihashi, Chie; Yamamoto, Masafumi; Eto, Tomoo; Konno, Yusuke; Okano, Hideyuki; Suematsu, Makoto; Sasaki, Erika

2014-01-01

Intracytoplasmic sperm injection (ICSI), an important method used to treat male subfertility, is applied in the transgenic technology of sperm-mediated gene transfer. However, no study has described successful generation of offspring using ICSI in the common marmoset, a small non-human primate used as a model for biomedical translational research. In this study, we investigated blastocyst development and the subsequent live offspring stages of marmoset oocytes matured in vitro and fertilized by ICSI. To investigate the optimal timing of performing ICSI, corrected immature oocytes were matured in vitro and ICSI was performed at various time points (1–2 h, 2–4 h, 4–6 h, 6–8 h, and 8–10 h after extrusion of the first polar body (PB)). Matured oocytes were then divided randomly into two groups: one was used for in vitro fertilization (IVF) and the other for ICSI. To investigate in vivo development of embryos followed by ICSI, 6-cell- to 8-cell-stage embryos and blastocysts were nonsurgically transferred into recipient marmosets. Although no significant differences were observed in the fertilization rate of blastocysts among ICSI timing after the first PB extrusion, the blastocyst rate at 1–2 h was lowest among groups at 2–4 h, 4–6 h, 6–8 h, and 8–10 h. Comparing ICSI to IVF, the fertilization rates obtained in ICSI were higher than in IVF (p>0.05). No significant difference was noted in the cleaved blastocyst rate between ICSI and IVF. Following the transfer of 37 ICSI blastocysts, 4 of 20 recipients became pregnant, while with the transfer of 21 6-cell- to 8-cell-stage ICSI embryos, 3 of 8 recipients became pregnant. Four healthy offspring were produced and grew normally. These are the first marmoset offspring produced by ICSI, making it an effective fertilization method for marmosets. PMID:24751978

Comparative experimental subcutaneous glanders and melioidosis in the common marmoset (Callithrix jacchus)

PubMed Central

Nelson, Michelle; Salguero, Francisco J; Dean, Rachel E; Ngugi, Sarah A; Smither, Sophie J; Atkins, Timothy P; Lever, Mark S

2014-01-01

Glanders and melioidosis are caused by two distinct Burkholderia species and have generally been considered to have similar disease progression. While both of these pathogens are HHS/CDC Tier 1 agents, natural infection with both these pathogens is primarily through skin inoculation. The common marmoset (Callithrix jacchus) was used to compare disease following experimental subcutaneous challenge. Acute, lethal disease was observed in marmosets following challenge with between 26 and 1.2 × 108 cfu Burkholderia pseudomallei within 22–85 h. The reproducibility and progression of the disease were assessed following a challenge of 1 × 102 cfu of B. pseudomallei. Melioidosis was characterised by high levels of bacteraemia, focal microgranuloma progressing to non-necrotic multifocal solid lesions in the livers and spleens and multi-organ failure. Lethal disease was observed in 93% of animals challenged with Burkholderia mallei, occurring between 5 and 10.6 days. Following challenge with 1 × 102 cfu of B. mallei, glanders was characterised with lymphatic spread of the bacteria and non-necrotic, multifocal solid lesions progressing to a multifocal lesion with severe necrosis and pneumonia. The experimental results confirmed that the disease pathology and presentation is strikingly different between the two pathogens. The marmoset provides a model of the human syndrome for both diseases facilitating the development of medical countermeasures. PMID:25477002

Characterization and pathogenesis of aerosolized eastern equine encephalitis in the common marmoset (Callithrix jacchus).

PubMed

Porter, Aimee I; Erwin-Cohen, Rebecca A; Twenhafel, Nancy; Chance, Taylor; Yee, Steven B; Kern, Steven J; Norwood, David; Hartman, Laurie J; Parker, Michael D; Glass, Pamela J; DaSilva, Luis

2017-02-07

Licensed antiviral therapeutics and vaccines to protect against eastern equine encephalitis virus (EEEV) in humans currently do not exist. Animal models that faithfully recapitulate the clinical characteristics of human EEEV encephalitic disease, including fever, drowsiness, anorexia, and neurological signs such as seizures, are needed to satisfy requirements of the Food and Drug Administration (FDA) for clinical product licensing under the Animal Rule. In an effort to meet this requirement, we estimated the median lethal dose and described the pathogenesis of aerosolized EEEV in the common marmoset (Callithrix jacchus). Five marmosets were exposed to aerosolized EEEV FL93-939 in doses ranging from 2.4 × 10 1 PFU to 7.95 × 10 5 PFU. The median lethal dose was estimated to be 2.05 × 10 2 PFU. Lethality was observed as early as day 4 post-exposure in the highest-dosed marmoset but animals at lower inhaled doses had a protracted disease course where humane study endpoint was not met until as late as day 19 post-exposure. Clinical signs were observed as early as 3 to 4 days post-exposure, including fever, ruffled fur, decreased grooming, and leukocytosis. Clinical signs increased in severity as disease progressed to include decreased body weight, subdued behavior, tremors, and lack of balance. Fever was observed as early as day 2-3 post-exposure in the highest dose groups and hypothermia was observed in several cases as animals became moribund. Infectious virus was found in several key tissues, including brain, liver, kidney, and several lymph nodes. Clinical hematology results included early neutrophilia, lymphopenia, and thrombocytopenia. Key pathological changes included meningoencephalitis and retinitis. Immunohistochemical staining for viral antigen was positive in the brain, retina, and lymph nodes. More intense and widespread IHC labeling occurred with increased aerosol dose. We have estimated the medial lethal dose of aerosolized EEEV and

Behavioral phenotypes associated with MPTP induction of partial lesions in common marmosets (Callithrix jacchus).

PubMed

Phillips, Kimberley A; Ross, Corinna N; Spross, Jennifer; Cheng, Catherine J; Izquierdo, Alyssa; Biju, K C; Chen, Cang; Li, Senlin; Tardif, Suzette D

2017-05-15

Parkinson's disease is a chronic neurodegenerative disorder with the core motor features of resting tremor, bradykinesia, rigidity, and postural instability. Non-motor symptoms also occur, and include cognitive dysfunction, mood disorders, anosmia (loss of smell), and REM sleep disturbances. As the development of medications and other therapies for treatment of non-motor symptoms is ongoing, it is essential to have animal models that aid in understanding the neural changes underlying non-motor PD symptoms and serve as a testing ground for potential therapeutics. We investigated several non-motor symptoms in 10 adult male marmosets using the MPTP model, with both the full (n=5) and partial (n=5) MPTP dosing regimens. Baseline data in numerous domains were collected prior to dosing; assessments in these same domains occurred post-dosing for 12 weeks. Marmosets given the partial MPTP dose (designed to mimic the early stages of the disease) differed significantly from marmosets given the full MPTP dose in several ways, including behavior, olfactory discrimination, cognitive performance, and social responses. Importantly, while spontaneous recovery of PD motor symptoms has been previously reported in studies of MPTP monkeys and cats, we did not observe recovery of any non-motor symptoms. This suggests that the neurochemical mechanisms behind the non-motor symptoms of PD, which appear years before the onset of symptoms, are independent of the striatal dopaminergic transmission. We demonstrate the value of assessing a broad range of behavioral change to detect non-motor impairment, anosmia, and differences in socially appropriate responses, in the marmoset MPTP model of early PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnetic resonance imaging mesencephalic tectum dimensions according to age and gender.

PubMed

Sabanciogullari, Vedat; Salk, Ismail; Balaban, Hatice; Oztoprak, Ibrahim; Kelkit, Seref; Cimen, Mehmet

2013-01-01

To analyze and classify normal MRI tectum length and colliculus dimensions according to age and gender. Tectum length and colliculus diameters were measured on the T1 midsagittal and axial cranial MR images in the radiology archive of 532 (344 women, 188 men) patients aged 37.36+/-21.49 (range: 4-91) years old on average, and with no disorders affecting the mesencephalic tectum. All 532 patients underwent clinical MR imaging of the cranium at the MRI Unit of Sivas Numune Hospital and Sivas Cumhuriyet University Hospital, Sivas, Turkey between February and December 2011. Although there was a positive linear correlation between tectum length and age, there was a negative correlation between the anteroposterior diameter of the colliculus superior and colliculus inferior and age (p<0.01). While tectum length (M3) increases with age, the anteroposterior diameter of the colliculus superior and inferior (M1 and M2) decreased (p<0.01). The colliculi were larger, and the tectum was longer in men. Although there was no difference in size between right and left superior colliculi, the left colliculus inferior was larger than the right one. In addition to the fact that normal mesencephalic tectum dimensions provide information on the brain development of individuals, they may also be beneficial for the detection and treatment of related pathologies.

Maternal gestational androgens are associated with decreased juvenile play in white-faced marmosets (Callithrix geoffroyi)

PubMed Central

Birnie, Andrew K.; Hendricks, Shelton E.; Smith, Adam S.; Milam, Ross; French, Jeffrey A.

2013-01-01

Exposure to androgens during prenatal development shapes both physiological and behavioral developmental trajectories. Notably, in rhesus macaques, prenatal androgen exposure has been shown to increase rough-and-tumble play, a prominent behavioral feature in males during the juvenile period in primates. While macaques are an Old World, polygamous species with marked sexually dimorphic behavior, New World callitrichine primates (marmosets and tamarins) live in cooperative breeding groups and are considered to be socially monogamous and exhibit minimal sexual dimorphism in social play, which suggests that androgen may affect this species in different ways compared to macaques. In addition, we previously described considerable variation in maternal androgen production during gestation in marmosets. Here we tested the association between this variation and variation in offspring rough-and-tumble play patterns in both males and females. We measured testosterone and androstenedione levels in urine samples collected from pregnant marmoset mothers and then observed their offspring's play behavior as juveniles (5–10 months of age). In contrast to findings in rhesus macaques, hierarchical regression analyses showed that higher gestational testosterone levels, primarily in the second semester, were associated with decreased rough-and-tumble play in juveniles, and this relationship appears to be driven more so by males than females. We found no reliable associations between gestational androstenedione and juvenile play behavior. Our findings provide evidence to suggest that normative variation in levels of maternal androgen during gestation may influence developmental behavioral trajectories in marmosets in a way that contradicts previous findings in Old World primates. PMID:22705955

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation

NASA Astrophysics Data System (ADS)

Kosugi, Akito; Takemi, Mitsuaki; Tia, Banty; Castagnola, Elisa; Ansaldo, Alberto; Sato, Kenta; Awiszus, Friedemann; Seki, Kazuhiko; Ricci, Davide; Fadiga, Luciano; Iriki, Atsushi; Ushiba, Junichi

2018-06-01

Objective. Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. Approach. ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. Main results. Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. Significance. Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation.

PubMed

Kosugi, Akito; Takemi, Mitsuaki; Tia, Banty; Castagnola, Elisa; Ansaldo, Alberto; Sato, Kenta; Awiszus, Friedemann; Seki, Kazuhiko; Ricci, Davide; Fadiga, Luciano; Iriki, Atsushi; Ushiba, Junichi

2018-06-01

Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

Quality of maternal and paternal care predicts later stress reactivity in the cooperatively-breeding marmoset (Callithrix geoffroyi).

PubMed

Birnie, Andrew K; Taylor, Jack H; Cavanaugh, Jon; French, Jeffrey A

2013-12-01

Variation in the early postnatal social environment can have lasting effects on hypothalamic-pituitary-adrenal (HPA) axis stress responses. Both rats and macaque monkeys subjected to low quality or abusive maternal care during the early postnatal period have more pronounced HPA responses to environmental stressors throughout development and into adulthood compared to animals reared in higher quality early maternal environments. However, little is known about the relative contributions to HPA stress response styles in developing offspring in species in which offspring care is routinely provided by group members other than the mother, such as in cooperatively breeding mammals. Marmoset monkeys exhibit cooperative offspring rearing, with fathers and older siblings providing care in addition to that provided by the mother. We evaluated the effects of early maternal, paternal, and older sibling care on HPA responses to social separation across development in captive white-faced marmoset offspring (Callithrix geoffroyi). We monitored offspring care by mothers, fathers, and older siblings in marmosets for the first 60 days of life. Later in development, each marmoset experienced three standardized social separation/novelty exposure stressors at 6, 12, and 18 months of age. During separation, we collected urine samples and analyzed them via enzyme immunoassay for cortisol levels. Infants that received higher rates of rejections from the entire family group showed higher cortisol responses to social separation. This relationship was found when mothers, fathers, and older siblings, were analyzed separately as well. No differences in cortisol responses were found between offspring that received high and low rates of carrying or high and low rates of licking and grooming by any group member. In the cooperatively breeding marmoset, early social cues from multiple classes of caregivers may influence HPA stress responses throughout the lifespan. Published by Elsevier Ltd.

Quality of Maternal and Paternal Care Predicts Later Stress Reactivity in the Cooperatively-Breeding Marmoset (Callithrix geoffroyi)

PubMed Central

Birnie, Andrew K.; Taylor, Jack H.; Cavanaugh, Jon; French, Jeffrey A.

2013-01-01

Variation in the early postnatal social environment can have lasting effects on hypothalamic-pituitary-adrenal (HPA) axis stress responses. Both rats and macaque monkeys subjected to low quality or abusive maternal care during the early postnatal period have more pronounced HPA responses to environmental stressors throughout development and into adulthood compared to animals reared in higher quality early maternal environments. However, little is known about the relative contributions to HPA stress response styles in developing offspring in species in which offspring care is routinely provided by group members other than the mother, such as in cooperatively breeding mammals. Marmoset monkeys exhibit cooperative offspring rearing, with fathers and older siblings providing care in addition to that provided by the mother. We evaluated the effects of early maternal, paternal, and older sibling care on HPA responses to social separation across development in captive white-faced marmoset offspring (Callithrix geoffroyi). We monitored offspring care by mothers, fathers, and older siblings in marmosets for the first 60 days of life. Later in development, each marmoset experienced three standardized social separation/novelty exposure stressors at 6, 12, and 18 months of age. During separation, we collected urine samples and analyzed them via enzyme immunoassay for cortisol levels. Infants that received higher rates of rejections from the entire family group showed higher cortisol responses to social separation. This relationship was found when mothers, fathers, and older siblings, were analyzed separately as well. No differences in cortisol responses were found between offspring that received high and low rates of carrying or high and low rates of licking and grooming by any group member. In the cooperatively breeding marmoset, early social cues from multiple classes of caregivers may influence HPA stress responses throughout the lifespan. PMID:24099861

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

Comparative experimental subcutaneous glanders and melioidosis in the common marmoset (Callithrix jacchus).

PubMed

Nelson, Michelle; Salguero, Francisco J; Dean, Rachel E; Ngugi, Sarah A; Smither, Sophie J; Atkins, Timothy P; Lever, Mark S

2014-12-01

Glanders and melioidosis are caused by two distinct Burkholderia species and have generally been considered to have similar disease progression. While both of these pathogens are HHS/CDC Tier 1 agents, natural infection with both these pathogens is primarily through skin inoculation. The common marmoset (Callithrix jacchus) was used to compare disease following experimental subcutaneous challenge. Acute, lethal disease was observed in marmosets following challenge with between 26 and 1.2 × 10(8) cfu Burkholderia pseudomallei within 22-85 h. The reproducibility and progression of the disease were assessed following a challenge of 1 × 10(2) cfu of B. pseudomallei. Melioidosis was characterised by high levels of bacteraemia, focal microgranuloma progressing to non-necrotic multifocal solid lesions in the livers and spleens and multi-organ failure. Lethal disease was observed in 93% of animals challenged with Burkholderia mallei, occurring between 5 and 10.6 days. Following challenge with 1 × 10(2) cfu of B. mallei, glanders was characterised with lymphatic spread of the bacteria and non-necrotic, multifocal solid lesions progressing to a multifocal lesion with severe necrosis and pneumonia. The experimental results confirmed that the disease pathology and presentation is strikingly different between the two pathogens. The marmoset provides a model of the human syndrome for both diseases facilitating the development of medical countermeasures. © 2014 Crown copyright. International Journal of Experimental Pathology © 2014 Company of the International Journal of Experimental Pathology (CIJEP).

LANGUAGE DEVELOPMENT. The developmental dynamics of marmoset monkey vocal production.

PubMed

Takahashi, D Y; Fenley, A R; Teramoto, Y; Narayanan, D Z; Borjon, J I; Holmes, P; Ghazanfar, A A

2015-08-14

Human vocal development occurs through two parallel interactive processes that transform infant cries into more mature vocalizations, such as cooing sounds and babbling. First, natural categories of sounds change as the vocal apparatus matures. Second, parental vocal feedback sensitizes infants to certain features of those sounds, and the sounds are modified accordingly. Paradoxically, our closest living ancestors, nonhuman primates, are thought to undergo few or no production-related acoustic changes during development, and any such changes are thought to be impervious to social feedback. Using early and dense sampling, quantitative tracking of acoustic changes, and biomechanical modeling, we showed that vocalizations in infant marmoset monkeys undergo dramatic changes that cannot be solely attributed to simple consequences of growth. Using parental interaction experiments, we found that contingent parental feedback influences the rate of vocal development. These findings overturn decades-old ideas about primate vocalizations and show that marmoset monkeys are a compelling model system for early vocal development in humans. Copyright © 2015, American Association for the Advancement of Science.

Binaural interaction in low-frequency neurons in inferior colliculus of the cat. II. Effects of changing rate and direction of interaural phase.

PubMed

Yin, T C; Kuwada, S

1983-10-01

We used the binaural beat stimulus to study the interaural phase sensitivity of inferior colliculus (IC) neurons in the cat. The binaural beat, produced by delivering tones of slightly different frequencies to the two ears, generates continuous and graded changes in interaural phase. Over 90% of the cells that exhibit a sensitivity to changes in the interaural delay also show a sensitivity to interaural phase disparities with the binaural beat. Cells respond with a burst of impulses with each complete cycle of the beat frequency. The period histogram obtained by binning the poststimulus time histogram on the beat frequency gives a measure of the interaural phase sensitivity of the cell. In general, there is good correspondence in the shapes of the period histograms generated from binaural beats and the interaural phase curves derived from interaural delays and in the mean interaural phase angle calculated from them. The magnitude of the beat frequency determines the rate of change of interaural phase and the sign determines the direction of phase change. While most cells respond in a phase-locked manner up to beat frequencies of 10 Hz, there are some cells tht will phase lock up to 80 Hz. Beat frequency and mean interaural phase angle are linearly related for most cells. Most cells respond equally in the two directions of phase change and with different rates of change, at least up to 10 Hz. However, some IC cells exhibit marked sensitivity to the speed of phase change, either responding more vigorously at low beat frequencies or at high beat frequencies. In addition, other cells demonstrate a clear directional sensitivity. The cells that show sensitivity to the direction and speed of phase changes would be expected to demonstrate a sensitivity to moving sound sources in the free field. Changes in the mean interaural phase of the binaural beat period histograms are used to determine the effects of changes in average and interaural intensity on the phase sensitivity

Oxidative Injury and Iron Redistribution Are Pathological Hallmarks of Marmoset Experimental Autoimmune Encephalomyelitis.

PubMed

Dunham, Jordon; Bauer, Jan; Campbell, Graham R; Mahad, Don J; van Driel, Nikki; van der Pol, Susanne M A; 't Hart, Bert A; Lassmann, Hans; Laman, Jon D; van Horssen, Jack; Kap, Yolanda S

2017-06-01

Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2. The EAE lesion-associated liberation of iron (due to loss of iron-containing myelin) was associated with altered expression of the iron metabolic markers FtH1, lactoferrin, hephaestin, and ceruloplasmin. The enhanced expression of oxidative damage markers in inflammatory lesions indicates that the enhanced antioxidant enzyme expression could not counteract reactive oxygen and nitrogen species-induced cellular damage, as is also observed in MS brains. This study demonstrates that oxidative injury and aberrant iron distribution are prominent pathological hallmarks of marmoset EAE thus making this model suitable for therapeutic intervention studies aimed at reducing oxidative stress and associated iron dysmetabolism. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Small but wise: Common marmosets (Callithrix jacchus) use acoustic signals as cues to avoid interactions with blonde capuchin monkeys (Sapajus flavius).

PubMed

Bastos, Monique; Medeiros, Karolina; Jones, Gareth; Bezerra, Bruna

2018-03-01

Vocalizations are often used by animals to communicate and mediate social interactions. Animals may benefit from eavesdropping on calls from other species to avoid predation and thus increase their chances of survival. Here we use both observational and experimental evidence to investigate eavesdropping and how acoustic signals may mediate interactions between two sympatric and endemic primate species (common marmosets and blonde capuchin monkeys) in a fragment of Atlantic Rainforest in Northeastern Brazil. We observed 22 natural vocal encounters between the study species, but no evident visual or physical contact over the study period. These two species seem to use the same area throughout the day, but at different times. We broadcasted alarm and long distance calls to and from both species as well as two control stimuli (i.e., forest background noise and a loud call from an Amazonian primate) in our playback experiments. Common marmosets showed anti-predator behavior (i.e., vigilance and flight) when exposed to blonde capuchin calls both naturally and experimentally. However, blonde capuchin monkeys showed no anti-predator behavior in response to common marmoset calls. Blonde capuchins uttered long distance calls and looked in the direction of the speaker following exposure to their own long distance call, whereas they fled when exposed to their own alarm calls. Both blonde capuchin monkeys and common marmosets showed fear behaviors in response to the loud call from a primate species unknown to them, and showed no apparent response to the forest background noise. Common marmoset responses to blonde capuchin calls suggests that the latter is a potential predator. Furthermore, common marmosets appear to be eavesdropping on calls from blonde capuchin monkeys to avoid potentially costly encounters with them. © 2018 Wiley Periodicals, Inc.

Resequencing of the common marmoset genome improves genome assemblies and gene-coding sequence analysis.

PubMed

Sato, Kengo; Kuroki, Yoko; Kumita, Wakako; Fujiyama, Asao; Toyoda, Atsushi; Kawai, Jun; Iriki, Atsushi; Sasaki, Erika; Okano, Hideyuki; Sakakibara, Yasubumi

2015-11-20

The first draft of the common marmoset (Callithrix jacchus) genome was published by the Marmoset Genome Sequencing and Analysis Consortium. The draft was based on whole-genome shotgun sequencing, and the current assembly version is Callithrix_jacches-3.2.1, but there still exist 187,214 undetermined gap regions and supercontigs and relatively short contigs that are unmapped to chromosomes in the draft genome. We performed resequencing and assembly of the genome of common marmoset by deep sequencing with high-throughput sequencing technology. Several different sequence runs using Illumina sequencing platforms were executed, and 181 Gbp of high-quality bases including mate-pairs with long insert lengths of 3, 8, 20, and 40 Kbp were obtained, that is, approximately 60× coverage. The resequencing significantly improved the MGSAC draft genome sequence. The N50 of the contigs, which is a statistical measure used to evaluate assembly quality, doubled. As a result, 51% of the contigs (total length: 299 Mbp) that were unmapped to chromosomes in the MGSAC draft were merged with chromosomal contigs, and the improved genome sequence helped to detect 5,288 new genes that are homologous to human cDNAs and the gaps in 5,187 transcripts of the Ensembl gene annotations were completely filled.

Strategies in Landmark Use by Children, Adults, and Marmoset Monkeys

ERIC Educational Resources Information Center

MacDonald, Suzanne E.; Spetch, Marcia L.; Kelly, Debbie M.; Cheng, Ken

2004-01-01

Common marmosets ("Callithrix jacchus jacchus"), human children, and human adults learned to find a goal that was located in the center of a square array of four identical landmarks. The location of the landmark array and corresponding goal varied across trials, so the task could not be solved without using the landmark array. In Experiment 1, a…

Treatment With CRH-1 Antagonist Antalarmin Reduces Behavioral and Endocrine Responses to Social Stressors in Marmosets (Callithrix kuhlii)

PubMed Central

FRENCH, JEFFREY A.; FITE, JEFFREY E.; JENSEN, HEATHER; OPAROWSKI, KATIE; RUKSTALIS, MICHAEL R.; FIX, HOLLY; JONES, BRENDA; MAXWELL, HEATHER; PACER, MOLLY; POWER, MICHAEL L.; SCHULKIN, JAY

2010-01-01

Corticotropin-releasing hormone (CRH) has multiple roles in coordinating the behavioral and endocrine responses to a host of environmental challenges, including social stressors. In the present study we evaluated the role of CRH in mediating responses to a moderate social stressor in Wied’s black tufted-eared marmosets (Callithrix kuhlii). Male and female marmosets (n = 14) were administered antalarmin (a selective CRH-1 receptor antagonist; 50μg/kg, p.o.) or vehicle in a blind, counterbalanced, crossover design. One hr after treatment, marmosets were separated from long-term pairmates and then housed alone in a novel enclosure for 7 hr. Behavior was recorded during separation and upon reunion with the partner, and urine samples for cortisol assay collected before, during, and after the intervention. Separation from partners elevated urinary cortisol concentrations over baseline for both conditions, but antalarmin treatment reduced the magnitude of the elevation. Antalarmin also lowered rates of behavioral patterns associated with arousal (alarm and ‘‘e-e’’ vocalizations, object manipulate/chew), but had no effect on contact calls, locomotory activity or alertness. Although most patterns of social behavior upon reunion with the partner were not affected by antalarmin, antalarmin-treated marmosets displayed more sexual behavior (mounts and copulations) upon reunion. These data indicate that antagonism of the CRH-1 receptor acts to reduce the magnitude of both endocrine and behavioral responses to a moderate social stressor without causing any overall reduction in alertness or general activity. This supports the hypothesis that CRH, acting through its type 1 receptor, is involved in coordinating the responses to anxiety-producing events. These results further suggest that the marmoset is a useful model for exploration of the role of CRH in mediating the behavioral and neuroendocrine responses to psychosocial stressors, particularly in the context of

Processing and representation of social communication sounds in the brainstem auditory system of bats

NASA Astrophysics Data System (ADS)

Pollak, George D.

2003-10-01

While bats are best known for their abilities to orient and capture prey via echolocation, they are also highly social animals who use a rich repertoire of species-specific sounds for social communication. This talk explores how communication signals are progressively transformed and represented in the ascending auditory system. One principal transformation that distinguishes the inferior colliculus from lower nuclei is a change from processing that emphasizes response homogeneity among the neuronal population in each lower nucleus, to one that emphasizes heterogeneity and selectivity in the inferior colliculus. Collicular neurons are selective in that each neuron fails to respond to some, or even all calls, even though those calls have energy that encroaches upon their excitatory response regions, and are heterogeneous since each collicular neuron responds to a different subset of calls. The transformation from homogeneity to heterogeneity may largely be a consequence of the difference in the ways that the various excitatory and inhibitory inputs distribute along frequency contours in lower nuclei compared to the inferior colliculus. One important consequence is that those features endow the population in the inferior colliculus with the ability to respond to any signal with a unique and pronounced spatiotemporal pattern of activity. [Work supported by NIH Grant No. DC 00268.

Individual identity and affective valence in marmoset calls: in vivo brain imaging with vocal sound playback.

PubMed

Kato, Masaki; Yokoyama, Chihiro; Kawasaki, Akihiro; Takeda, Chiho; Koike, Taku; Onoe, Hirotaka; Iriki, Atsushi

2018-05-01

As with humans, vocal communication is an important social tool for nonhuman primates. Common marmosets (Callithrix jacchus) often produce whistle-like 'phee' calls when they are visually separated from conspecifics. The neural processes specific to phee call perception, however, are largely unknown, despite the possibility that these processes involve social information. Here, we examined behavioral and whole-brain mapping evidence regarding the detection of individual conspecific phee calls using an audio playback procedure. Phee calls evoked sound exploratory responses when the caller changed, indicating that marmosets can discriminate between caller identities. Positron emission tomography with [ 18 F] fluorodeoxyglucose revealed that perception of phee calls from a single subject was associated with activity in the dorsolateral prefrontal, medial prefrontal, orbitofrontal cortices, and the amygdala. These findings suggest that these regions are implicated in cognitive and affective processing of salient social information. However, phee calls from multiple subjects induced brain activation in only some of these regions, such as the dorsolateral prefrontal cortex. We also found distinctive brain deactivation and functional connectivity associated with phee call perception depending on the caller change. According to changes in pupillary size, phee calls from a single subject induced a higher arousal level compared with those from multiple subjects. These results suggest that marmoset phee calls convey information about individual identity and affective valence depending on the consistency or variability of the caller. Based on the flexible perception of the call based on individual recognition, humans and marmosets may share some neural mechanisms underlying conspecific vocal perception.

Abundant Occurrence of Basal Radial Glia in the Subventricular Zone of Embryonic Neocortex of a Lissencephalic Primate, the Common Marmoset Callithrix jacchus

PubMed Central

Kelava, Iva; Reillo, Isabel; Murayama, Ayako Y.; Kalinka, Alex T.; Stenzel, Denise; Tomancak, Pavel; Matsuzaki, Fumio; Lebrand, Cécile; Sasaki, Erika; Schwamborn, Jens C.; Okano, Hideyuki; Borrell, Víctor

2012-01-01

Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type. PMID:22114084

Marmoset induced pluripotent stem cells: Robust neural differentiation following pretreatment with dimethyl sulfoxide.

PubMed

Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L; Guerra, Bernadette; Lanford, Robert E; Hornsby, Peter J

2015-07-01

The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS) cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05-2% dimethyl sulfoxide (DMSO) for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy. Copyright © 2015. Published by Elsevier B.V.

Other-regarding preferences in a non-human primate: Common marmosets provision food altruistically

PubMed Central

Burkart, Judith M.; Fehr, Ernst; Efferson, Charles; van Schaik, Carel P.

2007-01-01

Human cooperation is unparalleled in the animal world and rests on an altruistic concern for the welfare of genetically unrelated strangers. The evolutionary roots of human altruism, however, remain poorly understood. Recent evidence suggests a discontinuity between humans and other primates because individual chimpanzees do not spontaneously provide food to other group members, indicating a lack of concern for their welfare. Here, we demonstrate that common marmoset monkeys (Callithrix jacchus) do spontaneously provide food to nonreciprocating and genetically unrelated individuals, indicating that other-regarding preferences are not unique to humans and that their evolution did not require advanced cognitive abilities such as theory of mind. Because humans and marmosets are cooperative breeders and the only two primate taxa in which such unsolicited prosociality has been found, we conclude that these prosocial predispositions may emanate from cooperative breeding. PMID:18077409

Representation of Glossy Material Surface in Ventral Superior Temporal Sulcal Area of Common Marmosets

PubMed Central

Miyakawa, Naohisa; Banno, Taku; Abe, Hiroshi; Tani, Toshiki; Suzuki, Wataru; Ichinohe, Noritaka

2017-01-01

The common marmoset (Callithrix jacchus) is one of the smallest species of primates, with high visual recognition abilities that allow them to judge the identity and quality of food and objects in their environment. To address the cortical processing of visual information related to material surface features in marmosets, we presented a set of stimuli that have identical three-dimensional shapes (bone, torus or amorphous) but different material appearances (ceramic, glass, fur, leather, metal, stone, wood, or matte) to anesthetized marmoset, and recorded multiunit activities from an area ventral to the superior temporal sulcus (STS) using multi-shanked, and depth resolved multi-electrode array. Out of 143 visually responsive multiunits recorded from four animals, 29% had significant main effect only of the material, 3% only of the shape and 43% of both the material and the shape. Furthermore, we found neuronal cluster(s), in which most cells: (1) showed a significant main effect in material appearance; (2) the best stimulus was a glossy material (glass or metal); and (3) had reduced response to the pixel-shuffled version of the glossy material images. The location of the gloss-selective area was in agreement with previous macaque studies, showing activation in the ventral bank of STS. Our results suggest that perception of gloss is an important ability preserved across wide range of primate species. PMID:28367117

Representation of Glossy Material Surface in Ventral Superior Temporal Sulcal Area of Common Marmosets.

PubMed

Miyakawa, Naohisa; Banno, Taku; Abe, Hiroshi; Tani, Toshiki; Suzuki, Wataru; Ichinohe, Noritaka

2017-01-01

The common marmoset ( Callithrix jacchus ) is one of the smallest species of primates, with high visual recognition abilities that allow them to judge the identity and quality of food and objects in their environment. To address the cortical processing of visual information related to material surface features in marmosets, we presented a set of stimuli that have identical three-dimensional shapes (bone, torus or amorphous) but different material appearances (ceramic, glass, fur, leather, metal, stone, wood, or matte) to anesthetized marmoset, and recorded multiunit activities from an area ventral to the superior temporal sulcus (STS) using multi-shanked, and depth resolved multi-electrode array. Out of 143 visually responsive multiunits recorded from four animals, 29% had significant main effect only of the material, 3% only of the shape and 43% of both the material and the shape. Furthermore, we found neuronal cluster(s), in which most cells: (1) showed a significant main effect in material appearance; (2) the best stimulus was a glossy material (glass or metal); and (3) had reduced response to the pixel-shuffled version of the glossy material images. The location of the gloss-selective area was in agreement with previous macaque studies, showing activation in the ventral bank of STS. Our results suggest that perception of gloss is an important ability preserved across wide range of primate species.

Differential effects of dopaminergic drugs on spontaneous motor activity in the common marmoset following pretreatment with a bilateral brain infusion of 6-hydroxydopamine

PubMed Central

Nishime, Chiyoko; Inoue, Ryo; Nishinaka, Eiko; Kawai, Kenji; Urano, Koji; Tsutsumi, Hideki

2017-01-01

The differential effects of dopaminergic drugs with different pharmacological profiles were investigated with respect to spontaneous motor activity in the common marmoset following pretreatment with a bilateral brain infusion of 6-hydroxydopamine (6-OHDA). Three marmosets received infusions of 6-OHDA (either 30 or 40 μg/side) into the bilateral dopamine-rich area running from the substantia nigra to the striatum. The motor activity of the 6-OHDA marmosets was compared with that of three intact marmosets. Following the administration of apomorphine (0.5 and 1 mg/kg, subcutaneously), the 6-OHDA group showed a tendency toward a brief increase in activity counts, suggesting denervation supersensitivity at the dopamine receptors. After the administration of methamphetamine (1 and 2 mg/kg, subcutaneously), the 6-OHDA group showed a significant decrease in activity counts, indicating limited dopamine release from the degenerated neurons. After the administration of l-3,4-dihydroxyphenylalanine (10 and 20 mg/kg, orally), the 6-OHDA group showed a significant increase in activity counts without hyperexcitation, consistent with the contribution of exogenous l-3,4-dihydroxyphenylalanine toward dopamine synthesis in the degenerated neurons. The present findings indicate that bilateral brain infusion of 6-OHDA in the marmoset may have preclinical utility as a primate model for investigating the behavioral properties of dopaminergic drugs in brains with dopaminergic neural deficits. PMID:29099404

Social mobbing calls in common marmosets (Callithrix jacchus): effects of experience and associated cortisol levels.

PubMed

Clara, Elena; Tommasi, Luca; Rogers, Lesley J

2008-04-01

We compared the mobbing response to model snakes of two groups of captive-born common marmosets (Callithrix jacchus) differing in genetic relatedness, age and past experience. Mobbing vocalisations (tsik calls), other mobbing behaviour and attention to the stimulus were recorded for 2 min. intervals pre-exposure, during exposure to various stimuli and post-exposure. Marmosets in one group were vocally reactive to all stimuli, although more so to one particular stimulus resembling rearing snakes and modified images of it, whereas the marmosets in a younger and genetically unrelated group attended to the stimuli but made very few mobbing calls. The parent stock of the first group had suffered stress in early life and had developed a phobic response to a specific stimulus, which they had transmitted to their offspring. A third group, matching the older group in age range but genetically unrelated, was also found to be unresponsive to the stimulus that elicited the strongest response in the first group. Cortisol levels in samples of hair were assayed and a significant negative correlation was found between the number of tsik calls made during presentation of the stimuli and the cortisol level, showing that mobbing behaviour/behavioural reactivity is associated with low levels of physiological stress.

The effect of habitat acoustics on common marmoset vocal signal transmission.

PubMed

Morrill, Ryan J; Thomas, A Wren; Schiel, Nicola; Souto, Antonio; Miller, Cory T

2013-09-01

Noisy acoustic environments present several challenges for the evolution of acoustic communication systems. Among the most significant is the need to limit degradation of spectro-temporal signal structure in order to maintain communicative efficacy. This can be achieved by selecting for several potentially complementary processes. Selection can act on behavioral mechanisms permitting signalers to control the timing and occurrence of signal production to avoid acoustic interference. Likewise, the signal itself may be the target of selection, biasing the evolution of its structure to comprise acoustic features that avoid interference from ambient noise or degrade minimally in the habitat. Here, we address the latter topic for common marmoset (Callithrix jacchus) long-distance contact vocalizations, known as phee calls. Our aim was to test whether this vocalization is specifically adapted for transmission in a species-typical forest habitat, the Atlantic forests of northeastern Brazil. We combined seasonal analyses of ambient habitat acoustics with experiments in which pure tones, clicks, and vocalizations were broadcast and rerecorded at different distances to characterize signal degradation in the habitat. Ambient sound was analyzed from intervals throughout the day and over rainy and dry seasons, showing temporal regularities across varied timescales. Broadcast experiment results indicated that the tone and click stimuli showed the typically inverse relationship between frequency and signaling efficacy. Although marmoset phee calls degraded over distance with marked predictability compared with artificial sounds, they did not otherwise appear to be specially designed for increased transmission efficacy or minimal interference in this habitat. We discuss these data in the context of other similar studies and evidence of potential behavioral mechanisms for avoiding acoustic interference in order to maintain effective vocal communication in common marmosets. © 2013

The Effect of Habitat Acoustics on Common Marmoset Vocal Signal Transmission

PubMed Central

MORRILL, RYAN J.; THOMAS, A. WREN; SCHIEL, NICOLA; SOUTO, ANTONIO; MILLER, CORY T.

2013-01-01

Noisy acoustic environments present several challenges for the evolution of acoustic communication systems. Among the most significant is the need to limit degradation of spectro-temporal signal structure in order to maintain communicative efficacy. This can be achieved by selecting for several potentially complementary processes. Selection can act on behavioral mechanisms permitting signalers to control the timing and occurrence of signal production to avoid acoustic interference. Likewise, the signal itself may be the target of selection, biasing the evolution of its structure to comprise acoustic features that avoid interference from ambient noise or degrade minimally in the habitat. Here, we address the latter topic for common marmoset (Callithrix jacchus) long-distance contact vocalizations, known as phee calls. Our aim was to test whether this vocalization is specifically adapted for transmission in a species-typical forest habitat, the Atlantic forests of northeastern Brazil. We combined seasonal analyses of ambient habitat acoustics with experiments in which pure tones, clicks, and vocalizations were broadcast and rerecorded at different distances to characterize signal degradation in the habitat. Ambient sound was analyzed from intervals throughout the day and over rainy and dry seasons, showing temporal regularities across varied timescales. Broadcast experiment results indicated that the tone and click stimuli showed the typically inverse relationship between frequency and signaling efficacy. Although marmoset phee calls degraded over distance with marked predictability compared with artificial sounds, they did not otherwise appear to be specially designed for increased transmission efficacy or minimal interference in this habitat. We discuss these data in the context of other similar studies and evidence of potential behavioral mechanisms for avoiding acoustic interference in order to maintain effective vocal communication in common marmosets. PMID

Patterns on serpentine shapes elicit visual attention in marmosets (Callithrix jacchus).

PubMed

Wombolt, Jessica R; Caine, Nancy G

2016-09-01

Given the prevalence of threatening snakes in the evolutionary history, and modern-day environments of human and nonhuman primates, sensory, and perceptual abilities that allow for quick detection of, and appropriate response to snakes are likely to have evolved. Many studies have demonstrated that primates recognize snakes faster than other stimuli, and it is suggested that the unique serpentine shape is responsible for its quick detection. However, there are many nonthreatening serpentine shapes in the environment (e.g., vines) that are not threatening; therefore, other cues must be used to distinguish threatening from benign serpentine objects. In two experiments, we systematically evaluated how common marmosets (Callithrix jacchus) visually attend to specific snake-like features. In the first experiment, we examined if skin pattern is a cue that elicits increased visual inspection of serpentine shapes by measuring the amount of time the marmosets looked into a blind before, during, and after presentation of clay models with and without patterns. The marmosets spent the most time looking at the objects, both serpentine and triangle, that were etched with scales, suggesting that something may be uniquely salient about scales in evoking attention. In contrast, they showed relatively little interest in the unpatterned serpentine and control (a triangle) stimuli. In experiment 2, we replicated and extended the results of experiment 1 by adding additional stimulus conditions. We found that patterns on a serpentine shape generated more inspection than those same patterns on a triangle shape. We were unable to confirm that a scaled pattern is unique in its ability to elicit visual interest; the scaled models elicited similar looking times as line and star patterns. Our data provide a foundation for future research to examine how snakes are detected and identified by primates. Am. J. Primatol. 78:928-936, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals

Common marmosets show social plasticity and group-level similarity in personality

PubMed Central

Koski, Sonja E.; Burkart, Judith M.

2015-01-01

The social environment influences animal personality on evolutionary and immediate time scales. However, studies of animal personality rarely assess the effects of the social environment, particularly in species that live in stable groups with individualized relationships. We assessed personality experimentally in 17 individuals of the common marmoset, living in four groups. We found their personality to be considerably modified by the social environment. Marmosets exhibited relatively high plasticity in their behaviour, and showed ‘group-personality’, i.e. group-level similarity in the personality traits. In exploratory behaviour this was maintained only in the social environment but not when individuals were tested alone, suggesting that exploration tendency is subjected to social facilitation. Boldness, in contrast, showed higher consistency across the social and solitary conditions, and the group-level similarity in trait scores was sustained also outside of the immediate social environment. The ‘group-personality’ was not due to genetic relatedness, supporting that it was produced by social effects. We hypothesize that ‘group-personality’ may be adaptive for highly cooperative animals through facilitating cooperation among individuals with similar behavioural tendency. PMID:25743581

Analysis of the cross-talk of Epstein–Barr virus-infected B cells with T cells in the marmoset

PubMed Central

Dunham, Jordon; van Driel, Nikki; Eggen, Bart JL; Paul, Chaitali; ‘t Hart, Bert A; Laman, Jon D; Kap, Yolanda S

2017-01-01

Despite the well-known association of Epstein–Barr virus (EBV), a lymphocryptovirus (LCV), with multiple sclerosis, a clear pathogenic role for disease progression has not been established. The translationally relevant experimental autoimmune encephalomyelitis (EAE) model in marmoset monkeys revealed that LCV-infected B cells have a central pathogenic role in the activation of T cells that drive EAE progression. We hypothesized that LCV-infected B cells induce T-cell functions relevant for EAE progression. In the current study, we examined the ex vivo cross-talk between lymph node mononuclear cells (MNCs) from EAE marmosets and (semi-) autologous EBV-infected B-lymphoblastoid cell lines (B-LCLs). Results presented here demonstrate that infection with EBV B95-8 has a strong impact on gene expression profile of marmoset B cells, particularly those involved with antigen processing and presentation or co-stimulation to T cells. At the cellular level, we observed that MNC co-culture with B-LCLs induced decrease of CCR7 expression on T cells from EAE responder marmosets, but not in EAE monkeys without clinically evident disease. B-LCL interaction with T cells also resulted in significant loss of CD27 expression and reduced expression of IL-23R and CCR6, which coincided with enhanced IL-17A production. These results highlight the profound impact that EBV-infected B-LCL cells can have on second and third co-stimulatory signals involved in (autoreactive) T-cell activation. PMID:28243437

The Distinct Role of the Amygdala, Superior Colliculus and Pulvinar in Processing of Central and Peripheral Snakes

PubMed Central

Almeida, Inês; Soares, Sandra C.; Castelo-Branco, Miguel

2015-01-01

Introduction Visual processing of ecologically relevant stimuli involves a central bias for stimuli demanding detailed processing (e.g., faces), whereas peripheral object processing is based on coarse identification. Fast detection of animal shapes holding a significant phylogenetic value, such as snakes, may benefit from peripheral vision. The amygdala together with the pulvinar and the superior colliculus are implicated in an ongoing debate regarding their role in automatic and deliberate spatial processing of threat signals. Methods Here we tested twenty healthy participants in an fMRI task, and investigated the role of spatial demands (the main effect of central vs. peripheral vision) in the processing of fear-relevant ecological features. We controlled for stimulus dependence using true or false snakes; snake shapes or snake faces and for task constraints (implicit or explicit). The main idea justifying this double task is that amygdala and superior colliculus are involved in both automatic and controlled processes. Moreover the explicit/implicit instruction in the task with respect to emotion is not necessarily equivalent to explicit vs. implicit in the sense of endogenous vs. exogenous attention, or controlled vs. automatic processes. Results We found that stimulus-driven processing led to increased amygdala responses specifically to true snake shapes presented in the centre or in the peripheral left hemifield (right hemisphere). Importantly, the superior colliculus showed significantly biased and explicit central responses to snake-related stimuli. Moreover, the pulvinar, which also contains foveal representations, also showed strong central responses, extending the results of a recent single cell pulvinar study in monkeys. Similar hemispheric specialization was found across structures: increased amygdala responses occurred to true snake shapes presented to the right hemisphere, with this pattern being closely followed by the superior colliculus and the

Topography of eye-position sensitivity of saccades evoked electrically from the cat's superior colliculus.

PubMed

McIlwain, J T

1990-03-01

Saccades evoked electrically from the deep layers of the superior colliculus have been examined in the alert cat with its head fixed. Amplitudes of the vertical and horizontal components varied linearly with the starting position of the eye. The slopes of the linear-regression lines provided an estimate of the sensitivity of these components to initial eye position. In observations on 29 sites in nine cats, the vertical and horizontal components of saccades evoked from a given site were rarely influenced to the same degree by initial eye position. For most sites, the horizontal component was more sensitive than the vertical component. Sensitivities of vertical and horizontal components were lowest near the representations of the horizontal and vertical meridians, respectively, of the collicular retinotopic map, but otherwise exhibited no systematic retinotopic dependence. Estimates of component amplitudes for saccades evoked from the center of the oculomotor range also diverged significantly from those predicted from the retinotopic map. The results of this and previous studies indicate that electrical stimulation of the cat's superior colliculus cannot yield a unique oculomotor map or one that is in register everywhere with the sensory retinotopic map. Several features of these observations suggest that electrical stimulation of the colliculus produces faulty activation of a saccadic control system that computes target position with respect to the head and that small and large saccades are controlled differently.

Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus

PubMed Central

Zhu, Shaomei; Liu, Bochao; Xu, Yuxia; Sun, Yachun; Wang, Yilin; Wang, Yuanzhan; Shuai, Lifang; Chen, Zixuan; Allain, Jean-Pierre

2016-01-01

ABSTRACT A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection. Three animals used as controls were injected with phosphate-buffered saline (PBS) or GBV-B, respectively. Six of seven HCV NS2 to -4A chimera-infected marmosets exhibited consistent viremia and one showed transient viremia during the course of follow-up detection. All six infected animals with persistent circulating viremia presented characteristics typical of viral hepatitis, including viral RNA and proteins in hepatocytes and histopathological changes in liver tissue. Viremia was consistently detected for 5 to 54 weeks of follow-up. FK506 immunosuppression facilitated the establishment of persistent chimera infection in marmosets. An animal with chimera infection spontaneously cleared the virus in blood 7 weeks following the first inoculation, but viral-RNA persistence, low-level viral protein, and mild necroinflammation remained in liver tissue. The specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rechallenging, but no viremia was detected during 57 weeks of follow-up. The chimera-infected marmosets described can be used as a suitable small-primate animal model for studying novel antiviral drugs and T-cell-based vaccines against HCV infection. IMPORTANCE HCV infection causes approximately 70% of chronic hepatitis and is frequently associated with primary liver cancer globally. Chimpanzees have been used as a reliable primate model

Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus.

PubMed

Zhu, Shaomei; Li, Tingting; Liu, Bochao; Xu, Yuxia; Sun, Yachun; Wang, Yilin; Wang, Yuanzhan; Shuai, Lifang; Chen, Zixuan; Allain, Jean-Pierre; Li, Chengyao

2016-09-15

A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection. Three animals used as controls were injected with phosphate-buffered saline (PBS) or GBV-B, respectively. Six of seven HCV NS2 to -4A chimera-infected marmosets exhibited consistent viremia and one showed transient viremia during the course of follow-up detection. All six infected animals with persistent circulating viremia presented characteristics typical of viral hepatitis, including viral RNA and proteins in hepatocytes and histopathological changes in liver tissue. Viremia was consistently detected for 5 to 54 weeks of follow-up. FK506 immunosuppression facilitated the establishment of persistent chimera infection in marmosets. An animal with chimera infection spontaneously cleared the virus in blood 7 weeks following the first inoculation, but viral-RNA persistence, low-level viral protein, and mild necroinflammation remained in liver tissue. The specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rechallenging, but no viremia was detected during 57 weeks of follow-up. The chimera-infected marmosets described can be used as a suitable small-primate animal model for studying novel antiviral drugs and T-cell-based vaccines against HCV infection. HCV infection causes approximately 70% of chronic hepatitis and is frequently associated with primary liver cancer globally. Chimpanzees have been used as a reliable primate model for HCV infection

Different ovarian responses to potential mates underlie species-specific breeding strategies in common marmoset and Goeldi's monkey.

PubMed

Mattle, Franziska M E; Pryce, Christopher R; Anzenberger, Gustl

2008-08-01

Callitrichids are cooperative breeders, characterized by obligate twinning, extensive paternal care, and monopolization of reproduction by the dominant female. This is the case in the common marmoset, and in common marmoset groups of more than one adult female, subordinate females are typically acyclic consistent with infertility. However, one callitrichid, Goeldi's monkey, gives birth to singletons and exhibits low paternal care. Given these reproductive traits of Goeldi's monkey, we hypothesized that there would not be suppression of ovarian activity. To test this hypothesis, we applied non-invasive endocrine methods in a step-wise experiment with laboratory groups of both species. In each species, six pairs of sisters were studied alone, in visual contact with an unrelated male and in a polygynous trio with the male, and urine samples were collected for determination of oestrogen titres reflecting ovarian activity. Common marmoset sister pairs exhibited a marked difference in social status: during the study 5 of 6 dominant females conceived but only 1 of 6 subordinate females; the remaining 5 subordinates were acyclic at the end of the study, and instances of ovulation typically resulted in aggression. Goeldi's monkey sister pairs showed no status differences: in all pairs, however, both sisters exhibited a temporary cessation of ovarian cyclicity on trio formation, followed by ovulation and conception. We conclude that these marked differences in ovarian responses reflect the differences in inter-female competition for paternal caregiving resources. In common marmosets with high inter-female competition, suppression of ovulation functions to reduce aggression received by subordinate females; in Goeldi's monkey with low competition, temporary cessation of ovulation could facilitate female choice.

The atypical antipsychotic blonanserin reverses (+)-PD-128907- and ketamine-induced deficit in executive function in common marmosets.

PubMed

Kotani, Manato; Enomoto, Takeshi; Murai, Takeshi; Nakako, Tomokazu; Iwamura, Yoshihiro; Kiyoshi, Akihiko; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Nakayama, Tatsuo; Ogi, Yuji; Ikeda, Kazuhito

2016-05-15

Antagonism of the dopamine D3 receptor is considered a promising strategy for the treatment of cognitive impairment associated with schizophrenia. We have previously reported that the atypical antipsychotic blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptor antagonist, highly occupies dopamine D3 receptors at its antipsychotic dose range in rats. In the present study, we evaluated the effects of blonanserin on executive function in common marmosets using the object retrieval with detour (ORD) task. The dopamine D3 receptor-preferring agonist (+)-PD-128907 at 1mg/kg decreased success rate in the difficult trial, but not in the easy trial. Since the difference between the two trials is only cognitive demand, our findings indicate that excess activation of dopamine D3 receptors impairs executive function in common marmosets. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by (+)-PD-128907 in the difficult trial. This finding indicates that blonanserin has beneficial effect on executive function deficit induced by activation of the dopamine D3 receptor in common marmosets. Next, and based on the glutamatergic hypothesis of schizophrenia, the common marmosets were treated with the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. Ketamine at sub-anesthetic doses decreased success rate in the difficult trial, but not in the easy trial. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by ketamine in the difficult trial. The findings of this study suggest that blonanserin might have beneficial effect on executive dysfunction in patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of mammary epithelial stem/progenitor cells and their changes with aging in common marmosets.

PubMed

Wu, Anqi; Dong, Qiaoxiang; Gao, Hui; Shi, Yuanshuo; Chen, Yuanhong; Zhang, Fuchuang; Bandyopadhyay, Abhik; Wang, Danhan; Gorena, Karla M; Huang, Changjiang; Tardif, Suzette; Nathanielsz, Peter W; Sun, Lu-Zhe

2016-08-25

Age is the number one risk factor for breast cancer, yet the underlying mechanisms are unexplored. Age-associated mammary stem cell (MaSC) dysfunction is thought to play an important role in breast cancer carcinogenesis. Non-human primates with their close phylogenetic relationship to humans provide a powerful model system to study the effects of aging on human MaSC. In particular, the common marmoset monkey (Callithrix jacchus) with a relatively short life span is an ideal model for aging research. In the present study, we characterized for the first time the mammary epithelial stem/progenitor cells in the common marmoset. The MaSC-enriched cells formed four major types of morphologically distinct colonies when cultured on plates pre-seeded with irradiated NIH3T3 fibroblasts, and were also capable of forming mammospheres in suspension culture and subsequent formation of 3D organoids in Matrigel culture. Most importantly, these 3D organoids were found to contain stem/progenitor cells that can undergo self-renewal and multi-lineage differentiation both in vitro and in vivo. We also observed a significant decrease of luminal-restricted progenitors with age. Our findings demonstrate that common marmoset mammary stem/progenitor cells can be isolated and quantified with established in vitro and in vivo assays used for mouse and human studies.

Parturition Signaling by Visual Cues in Female Marmosets (Callithrix jacchus).

PubMed

Moreira, Laís Alves Antonio; de Oliveira, Danilo Gustavo Rodrigues; de Sousa, Maria Bernardete Cordeiro; Pessoa, Daniel Marques Almeida

2015-01-01

New World monkeys have polymorphic color vision, in which all males and some females are dichromats, while most females are trichromats. There is little consensus about which selective pressures fashioned primate color vision, although detection of food, mates and predators has been hypothesized. Behavioral evidence shows that males from different species of Neotropical primates seem to perceive the timing of female conception and gestation, although, no signals fulfilling this function have been identified. Therefore, we used visual models to test the hypothesis that female marmosets show chromatic and/or achromatic cues that may indicate the time of parturition for male and female conspecifics. By recording the reflectance spectra of female marmosets' (Callithrix jacchus) sexual skin, and running chromatic and achromatic discrimination models, we found that both variables fluctuate during the weeks that precede and succeed parturition, forming "U" and inverted "U" patterns for chromatic and achromatic contrast, respectively. We suggest that variation in skin chroma and luminance might be used by female helpers and dominant females to identify the timing of birth, while achromatic variations may be used as clues by potential fathers to identify pregnancy stage in females and prepare for paternal burdens as well as to detect oestrus in the early post-partum period.

Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

PubMed

Chaplin, Tristan A; Allitt, Benjamin J; Hagan, Maureen A; Price, Nicholas S C; Rajan, Ramesh; Rosa, Marcello G P; Lui, Leo L

2017-09-01

Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments. NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural

Flibanserin and 8-OH-DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair-bond quality

PubMed Central

Aubert, Yves; Gustison, Morgan L.; Gardner, Lindsey A.; Bohl, Michael A.; Lange, Jason R.; Allers, Kelly A.; Sommer, Bernd; Datson, Nicole A.; Abbott, David H.

2018-01-01

Introduction Psychopathological origins of personally distressing, hypoactive sexual desire disorder (HSDD) in women are unknown, but are generally attributed to an inhibitory neural regulator, serotonin (5-HT). Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, shows promise as a treatment for HSDD. Aim To test the hypothesis that female marmoset sexual behavior is enhanced by flibanserin and diminished by 8-OH-DPAT, in order to evaluate the efficacy of serotonergic modulation of female sexual behavior in a pairmate social setting comparable to humans. Methods Sexual and social behavior were examined in 8 female marmoset monkeys receiving daily flibanserin (15mg/kg), 8-OH-DPAT (0.1 mg/kg) or corresponding vehicle for 15–16 weeks in a counterbalanced, within-subject design, while housed in long-term, stable male-female pairs. Main outcome measures Marmoset pairmate interactions, including sexual and social behavior, were scored during weeks 5–6 of daily flibanserin, 8-OH-DPAT or vehicle treatment. 24-h pharmacokinetic profiles of the drugs and their metabolites, as well as drug-induced acute symptoms of the 5-HT behavioral syndrome were also assessed. Results 2-way analysis of variance reveals that flibanserin-treated females attract more male sexual interest (p = .020) and trigger increased grooming (p = .001) between partners. In contrast, 8-OH-DPAT-treated females show increased rejection of male sexual advances (p = .024), a tendency for decreased male sexual interest (p = .080), and increased aggression with their male pairmates (p = .049). Conclusions While 8-OH-DPAT-treated female marmosets display decreased sexual receptivity and increased aggressive interactions with their male pairmates, flibanserin-treated female marmosets demonstrate increased affiliative behavior with their male pairmates. Such pro-affiliation attributes may underly flibanserin’s effectiveness in treating HSDD in women. PMID:22304661

Striatal and extrastriatal dopamine release in the common marmoset brain measured by positron emission tomography and [(18)F]fallypride.

PubMed

Ota, Miho; Ogawa, Shintaro; Kato, Koichi; Masuda, Chiaki; Kunugi, Hiroshi

2015-12-01

Previous studies have demonstrated that patients with schizophrenia show greater sensitivity to psychostimulants than healthy subjects. Sensitization to psychostimulants and resultant alteration of dopaminergic neurotransmission in rodents has been suggested as a useful model of schizophrenia. This study sought to examine the use of methylphenidate as a psychostimulant to induce dopamine release and that of [(18)F]fallypride as a radioligand to quantify the release in a primate model of schizophrenia. Four common marmosets were scanned by positron emission tomography twice, before and after methylphenidate challenge, to evaluate dopamine release. Four other marmosets were sensitized by repeated methamphetamine (MAP) administration. Then, they were scanned twice, before and after methylphenidate challenge, to evaluate whether MAP-sensitization induced greater sensitivity to methylphenidate. We revealed a main effect of the methylphenidate challenge but not the MAP pretreatment on the striatal binding potential. These results suggest that methylphenidate-induced striatal dopamine release in the common marmoset could be evaluated by [(18)F]fallypride. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Predictive Value of Parkinsonian Primates in Pharmacologic Studies: A Comparison between the Macaque, Marmoset, and Squirrel Monkey.

PubMed

Veyres, Nicolas; Hamadjida, Adjia; Huot, Philippe

2018-05-01

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate is the gold-standard animal model of Parkinson disease (PD) and has been used to assess the effectiveness of experimental drugs on dyskinesia, parkinsonism, and psychosis. Three species have been used in most studies-the macaque, marmoset, and squirrel monkey-the last much less so than the first two species; however, the predictive value of each species at forecasting clinical efficacy, or lack thereof, is poorly documented. Here, we have reviewed all the published literature detailing pharmacologic studies that assessed the effects of experimental drugs on dyskinesia, parkinsonism, and psychosis in each of these species and have calculated their predictive value of success and failure at the clinical level. We found that, for dyskinesia, the macaque has a positive predictive value of 87.5% and a false-positive rate of 38.1%, whereas the marmoset has a positive predictive value of 76.9% and a false-positive rate of 15.6%. For parkinsonism, the macaque has a positive predictive value of 68.2% and a false-positive rate of 44.4%, whereas the marmoset has a positive predictive value of 86.9% and a false-positive rate of 41.7%. No drug that alleviates psychosis in the clinic has shown efficacy at doing so in the macaque, whereas the marmoset has 100% positive predictive value. The small number of studies conducted in the squirrel monkey precluded us from calculating its predictive efficacy. We hope our results will help in the design of pharmacologic experiments and will facilitate the drug discovery and development process in PD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Methylmercury poisoning in common marmosets--a study of selective vulnerability within the cerebral cortex.

PubMed

Eto, K; Yasutake, A; Kuwana, T; Korogi, Y; Akima, M; Shimozeki, T; Tokunaga, H; Kaneko, Y

2001-01-01

Neuropathological lesions found in chronic human Minamata disease tend to be localized in the calcarine cortex of occipital lobes, the pre- and postcentral lobuli, and the temporal gyri. The mechanism for the selective vulnerability is still not clear, though several hypotheses have been proposed. One hypothesis is vascular and postulates that the lesions are the result of ischemia secondary to compression of sulcal arteries from methylmercury-induced cerebral edema. To test this hypothesis, we studied common marmosets because the cerebrum of marmosets has 2 distinct deep sulci, the calcarine and Sylvian fissures. MRI analysis, mercury assays of tissue specimens, histologic and histochemical studies of the brain are reported and discussed. Brains sacrificed early after exposure to methylmercury showed high contents of methylmercury and edema of the cerebral white matter. These results may explain the selective cortical degeneration along the deep cerebral fissures or sulci.

Intravenous administration of the adeno-associated virus-PHP.B capsid fails to upregulate transduction efficiency in the marmoset brain.

PubMed

Matsuzaki, Yasunori; Konno, Ayumu; Mochizuki, Ryuta; Shinohara, Yoichiro; Nitta, Keisuke; Okada, Yukihiro; Hirai, Hirokazu

2018-02-05

Intravenous administration of adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV9 containing seven amino acid insertions, results in a greater permeability of the blood brain barrier (BBB) than standard AAV9 in mice, leading to highly efficient and global transduction of the central nervous system (CNS). The present study aimed to examine whether the enhanced BBB penetrance of AAV-PHP.B observed in mice also occurs in non-human primates. Thus, a young adult (age, 1.6 years) and an old adult (age, 7.2 years) marmoset received an intravenous injection of AAV-PHP.B expressing enhanced green fluorescent protein (EGFP) under the control of the constitutive CBh promoter (a hybrid of cytomegalovirus early enhancer and chicken β-actin promoter). Age-matched control marmosets were treated with standard AAV9-capsid vectors. The animals were sacrificed 6 weeks after the viral injection. Based on the results, only limited transduction of neurons (0-2%) and astrocytes (0.1-2.5%) was observed in both AAV-PHP.B- and AAV9-treated marmosets. One noticeable difference between AAV-PHP.B and AAV9 was the marked transduction of the peripheral dorsal root ganglia neurons. Indeed, the soma and axons in the projection from the spinal cord to the nucleus cuneatus in the medulla oblongata were strongly labeled with EGFP by AAV-PHP.B. Thus, except for the peripheral dorsal root ganglia neurons, the AAV-PHP.B transduction efficiency in the CNS of marmosets was comparable to that of AAV9 vectors. Copyright © 2017 Elsevier B.V. All rights reserved.

Vocal Learning via Social Reinforcement by Infant Marmoset Monkeys.

PubMed

Takahashi, Daniel Y; Liao, Diana A; Ghazanfar, Asif A

2017-06-19

For over half a century now, primate vocalizations have been thought to undergo little or no experience-dependent acoustic changes during development [1]. If any changes are apparent, then they are routinely (and quite reasonably) attributed to the passive consequences of growth. Indeed, previous experiments on squirrel monkeys and macaque monkeys showed that social isolation [2, 3], deafness [2], cross-fostering [4] and parental absence [5] have little or no effect on vocal development. Here, we explicitly test in marmoset monkeys-a very vocal and cooperatively breeding species [6]-whether the transformation of immature into mature contact calls by infants is influenced by contingent parental vocal feedback. Using a closed-loop design, we experimentally provided more versus less contingent vocal feedback to twin infant marmoset monkeys over their first 2 months of life, the interval during which their contact calls transform from noisy, immature calls to tonal adult-like "phee" calls [7, 8]. Infants who received more contingent feedback had a faster rate of vocal development, producing mature-sounding contact calls earlier than the other twin. The differential rate of vocal development was not linked to genetics, perinatal experience, or body growth; nor did the amount of contingency influence the overall rate of spontaneous vocal production. Thus, we provide the first experimental evidence for production-related vocal learning during the development of a nonhuman primate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mirror Neurons in a New World Monkey, Common Marmoset

PubMed Central

Suzuki, Wataru; Banno, Taku; Miyakawa, Naohisa; Abe, Hiroshi; Goda, Naokazu; Ichinohe, Noritaka

2015-01-01

Mirror neurons respond when executing a motor act and when observing others' similar act. So far, mirror neurons have been found only in macaques, humans, and songbirds. To investigate the degree of phylogenetic specialization of mirror neurons during the course of their evolution, we determined whether mirror neurons with similar properties to macaques occur in a New World monkey, the common marmoset (Callithrix jacchus). The ventral premotor cortex (PMv), where mirror neurons have been reported in macaques, is difficult to identify in marmosets, since no sulcal landmarks exist in the frontal cortex. We addressed this problem using “in vivo” connection imaging methods. That is, we first identified cells responsive to others' grasping action in a clear landmark, the superior temporal sulcus (STS), under anesthesia, and injected fluorescent tracers into the region. By fluorescence stereomicroscopy, we identified clusters of labeled cells in the ventrolateral frontal cortex, which were confirmed to be within the ventrolateral frontal cortex including PMv after sacrifice. We next implanted electrodes into the ventrolateral frontal cortex and STS and recorded single/multi-units under an awake condition. As a result, we found neurons in the ventrolateral frontal cortex with characteristic “mirror” properties quite similar to those in macaques. This finding suggests that mirror neurons occur in a common ancestor of New and Old World monkeys and its common properties are preserved during the course of primate evolution. PMID:26696817

Single Unit Recordings of Cells Responsive to Visual, Somatic, Acoustic, and Noxious Stimuli in the Superior Colliculus of the Golden Hamster.

DTIC Science & Technology

1978-08-01

Acoustic, and Noxious Stimuli Thesis in the Superior Colliculus of the Golden 6. PERFORMING OG. REPORT NUMBER Hamster -. _ // 7. AUTHOR( a ) S. CONTRACT...OR GRANT NUMBER(s) James P. Dixon I - "JV 9. PERF 7 MING ORGANIZATION NAME A D10. PROGRAM ELEMENT, PROJECT, TASK AFIT Student at: Virginia...studied in the superior colliculus of the golden hamster. A laminar organiza- tion was observed with cells in the superficial layers responding exclusively

The transcriptomes of novel marmoset monkey embryonic stem cell lines reflect distinct genomic features

PubMed Central

Debowski, Katharina; Drummer, Charis; Lentes, Jana; Cors, Maren; Dressel, Ralf; Lingner, Thomas; Salinas-Riester, Gabriela; Fuchs, Sigrid; Sasaki, Erika; Behr, Rüdiger

2016-01-01

Embryonic stem cells (ESCs) are useful for the study of embryonic development. However, since research on naturally conceived human embryos is limited, non-human primate (NHP) embryos and NHP ESCs represent an excellent alternative to the corresponding human entities. Though, ESC lines derived from naturally conceived NHP embryos are still very rare. Here, we report the generation and characterization of four novel ESC lines derived from natural preimplantation embryos of the common marmoset monkey (Callithrix jacchus). For the first time we document derivation of NHP ESCs derived from morula stages. We show that quantitative chromosome-wise transcriptome analyses precisely reflect trisomies present in both morula-derived ESC lines. We also demonstrate that the female ESC lines exhibit different states of X-inactivation which is impressively reflected by the abundance of the lncRNA X inactive-specific transcript (XIST). The novel marmoset ESC lines will promote basic primate embryo and ESC studies as well as preclinical testing of ESC-based regenerative approaches in NHP. PMID:27385131

The transcriptomes of novel marmoset monkey embryonic stem cell lines reflect distinct genomic features.

PubMed

Debowski, Katharina; Drummer, Charis; Lentes, Jana; Cors, Maren; Dressel, Ralf; Lingner, Thomas; Salinas-Riester, Gabriela; Fuchs, Sigrid; Sasaki, Erika; Behr, Rüdiger

2016-07-07

Embryonic stem cells (ESCs) are useful for the study of embryonic development. However, since research on naturally conceived human embryos is limited, non-human primate (NHP) embryos and NHP ESCs represent an excellent alternative to the corresponding human entities. Though, ESC lines derived from naturally conceived NHP embryos are still very rare. Here, we report the generation and characterization of four novel ESC lines derived from natural preimplantation embryos of the common marmoset monkey (Callithrix jacchus). For the first time we document derivation of NHP ESCs derived from morula stages. We show that quantitative chromosome-wise transcriptome analyses precisely reflect trisomies present in both morula-derived ESC lines. We also demonstrate that the female ESC lines exhibit different states of X-inactivation which is impressively reflected by the abundance of the lncRNA X inactive-specific transcript (XIST). The novel marmoset ESC lines will promote basic primate embryo and ESC studies as well as preclinical testing of ESC-based regenerative approaches in NHP.

Responses to pure tones and linear FM components of the CF-FM biosonar signal by single units in the inferior colliculus of the mustached bat.

PubMed

O'Neill, W E

1985-12-01

The responses of 682 single-units in the inferior colliculus (IC) of 13 mustached bats (Pteronotus parnellii parnellii) were measured using pure tones (CF), frequency modulations (FM) and pairs of CF-FM signals mimicking the species' biosonar signal, which are stimuli known to be essential to the responses of CF/CF and FM-FM facilitation neurons in auditory cortex. Units were arbitrarily classified into 'reference frequency' (RF), 'FM2' and 'Non-echolocation' (NE) categories according to the relationship of their best frequencies (BF) to the biosonar signal frequencies. RF units have high Q10dB values and are tuned to the reference frequency of each bat, which ranged between 60.73 and 62.73 kHz. FM2 units had BF's between 50 and 60 kHz, while NE units had BF's outside the ranges of the RF and FM2 classes. PST histograms of the responses revealed discharge patterns such as 'onset', 'onset-bursting' (most common), 'on-off', 'tonic-on','pauser', and 'chopper'. Changes in discharge patterns usually resulted from changes in the frequency and/or intensity of the stimuli, most often involving a change from onset-bursting to on-off. Different patterns were also elicited by CF and FM stimuli. Frequency characteristics and thresholds to CF and FM stimuli were measured. RF neurons were very sharply tuned with Q10dB's ranging from 50-360. Most (92%) also responded to FM2 stimuli, but 78% were significantly more sensitive (greater than 5 dB) to CF stimuli, and only 3% had significantly lower thresholds to FM2. The best initial frequency for FM2 sweeps in RF units was 65.35 +/- 2.138 kHz (n = 118), well above the natural frequency of the 2nd harmonic. FM2 and NE units were indistinguishable from each other, but were quite different from RF units: 41% of these two classes had lower thresholds to CF, 49% were about equally sensitive, and 10% had lower thresholds to FM. For FM2 units, mean best initial frequency for FM was 60.94 kHz +/- 3.162 kHz (n = 114), which is closely matched

Quality of common marmoset (Callithrix jacchus) oocytes collected after ovarian stimulation.

PubMed

Kanda, Akifumi; Nobukiyo, Asako; Yoshioka, Miyuki; Hatakeyama, Teruhiko; Sotomaru, Yusuke

2018-01-15

The common marmoset (Callithrix jacchus) is an experimental animal that is considered suitable for the creation of next-generation human disease models. It has recently been used in the reproductive technology field. Oocytes can be effectively collected from female marmosets via ovarian stimulation with injections of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). The oocytes, collected about 28 h after the hCG injection, include both premature oocytes and postmature (in vivo matured; IVO) oocytes, and the premature oocytes can be matured by in vitro culture (in vitro matured; IVM). Although IVM and IVO oocytes are equivalent in appearance at the MII stage, it remains unclear whether there are differences in their properties. Therefore, we investigated their in vitro fertilization and developmental capacities and cytoskeletal statuses. Our findings revealed that the IVM and IVO oocytes had similar fertilization rates but that no IVO oocytes could develop to the blastocyst stage. Additionally, IVO oocytes showed abnormal cytoskeletal formation. It is concluded that IVM oocytes maintain normal function, whereas IVO oocytes would be affected by aging and other factors when they remain for a long time in the ovary. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset

PubMed Central

McKinnell, Chris; Mitchell, Rod T.; Walker, Marion; Morris, Keith; Kelnar, Chris J.H.; Wallace, W. Hamish; Sharpe, Richard M.

2009-01-01

BACKGROUND Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (CIS) or testicular germ cell tumours (TGCT). METHODS Pregnant female marmosets were dosed from ∼7–15 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (1–5 days; n = 6) or in adulthood (n = 5). In another study, newborn males (n = 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at ∼4 days of age. RESULTS Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for CIS or TGCT. CONCLUSIONS Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance. PMID:19491204

Advantages and Risks of Husbandry and Housing Changes to Improve Animal Wellbeing in a Breeding Colony of Common Marmosets (Callithrix jacchus)

PubMed Central

Bakker, Jaco; Ouwerling, Boudewijn; Heidt, Peter J; Kondova, Ivanela; Langermans, Jan AM

2015-01-01

Between 1975 and 2014, housing conditions for laboratory-housed marmosets changed dramatically after the introduction of new guidelines designed to improve their care and wellbeing. According to these guidelines, our facility provided marmosets with outside enclosures, switched to deep litter as bedding material, and discontinued the use of disinfectant agents in animal enclosures. However, both deep litter and access to outside enclosures hypothetically increase the risk of potential exposure to pathogenic microorganisms. We evaluated whether these housing and husbandry modifications constituted an increased veterinary risk for laboratory-housed common marmosets (Callithrix jacchus). After the animals had been exposed to these new housing conditions for 2.5 y, we examined their intestinal bacterial flora and feces, the deep litter, and insects present in the housing. In addition, we assessed the marmosets’ general health and the effect of outdoor housing on, for example, vitamin D levels. Although numerous bacterial strains—from nonpathogenic to potentially pathogenic—were cultured, we noted no increase in illness, mortality, or breeding problems related to this environmental microflora. Housing laboratory marmosets in large enriched cages, with both indoor and outdoor enclosures, providing them with deep litter, and eliminating the use of disinfectants present an increased veterinary risk. However, after evaluating all of the collected data, we estimate that the veterinary risk of the new housing conditions is minimal to none in terms of clinical disease, disease outbreaks, abnormal behavior, and negative effects on reproduction. PMID:26045452

Oxytocin is associated with infant-care behavior and motivation in cooperatively breeding marmoset monkeys.

PubMed

Finkenwirth, Christa; Martins, Eloisa; Deschner, Tobias; Burkart, Judith M

2016-04-01

The neurohormone oxytocin (OT) is positively involved in the regulation of parenting and social bonding in mammals, and may thus also be important for the mediation of alloparental care. In cooperatively breeding marmosets, infants are raised in teamwork by parents and adult and sub-adult non-reproductive helpers (usually older siblings). Despite high intrinsic motivation, which may be mediated by hormonal priming, not all individuals are always equally able to contribute to infant-care due to competition among care-takers. Among the various care-taking behaviors, proactive food sharing may reflect motivational levels best, since it can be performed ad libitum by several individuals even if competition among surplus care-takers constrains access to infants. Our aim was to study the link between urinary OT levels and care-taking behaviors in group-living marmosets, while taking affiliation with other adults and infant age into account. Over eight reproductive cycles, 26 individuals were monitored for urinary baseline OT, care-taking behaviors (baby-licking, -grooming, -carrying, and proactive food sharing), and adult-directed affiliation. Mean OT levels were generally highest in female breeders and OT increased significantly in all individuals after birth. During early infancy, high urinary OT levels were associated with increased infant-licking but low levels of adult-affiliation, and during late infancy, with increased proactive food sharing. Our results show that, in marmoset parents and alloparents, OT is positively involved in the regulation of care-taking, thereby reflecting the changing needs during infant development. This particularly included behaviors that are more likely to reflect intrinsic care motivation, suggesting a positive link between OT and motivational regulation of infant-care. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain.

PubMed

Ono, Munenori; Bishop, Deborah C; Oliver, Douglas L

2016-02-12

Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound.

Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain

PubMed Central

Ono, Munenori; Bishop, Deborah C.; Oliver, Douglas L.

2016-01-01

Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound. PMID:26867811

Effects of aging and rifampicin pretreatment on the pharmacokinetics of human cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol and midazolam in common marmosets genotyped for cytochrome P450 2C19.

PubMed

Toda, Akiko; Uehara, Shotaro; Inoue, Takashi; Utoh, Masahiro; Kusama, Takashi; Shimizu, Makiko; Uno, Yasuhiro; Mogi, Masayuki; Sasaki, Erika; Yamazaki, Hiroshi

2018-07-01

1. The pharmacokinetics were investigated for human cytochrome P450 probes after single intravenous and oral administrations of 0.20 and 1.0 mg/kg, respectively, of caffeine, warfarin, omeprazole, metoprolol and midazolam to aged (10-14 years old, n = 4) or rifampicin-treated/young (3 years old, n = 3) male common marmosets all genotyped as heterozygous for a cytochrome P450 2C19 variant. 2. Slopes of the plasma concentration-time curves after intravenous administration of warfarin and midazolam were slightly, but significantly (two-way analysis of variance), decreased in aged marmosets compared with young marmosets. The mean hepatic clearances determined by in silico fitting for individual pharmacokinetic models of warfarin and midazolam in the aged group were, respectively, 23% and 56% smaller than those for the young group. 3. Significantly enhanced plasma clearances of caffeine, warfarin, omeprazole and midazolam were evident in young marmosets pretreated with rifampicin (25 mg/kg daily for 4 days). Two- to three-fold increases in hepatic intrinsic clearance values were observed in the individual pharmacokinetic models. 4. The in vivo dispositions of multiple simultaneously administered drugs in old, young and P450-enzyme-induced marmosets were elucidated. The results suggest that common marmosets could be experimental models for aged, induced or polymorphic P450 enzymes in P450-dependent drug metabolism studies.

An Embedded 4-Channel Receive-Only RF Coil Array for fMRI Experiments of the Somatosensory Pathway in Conscious Awake Marmosets at 7T

PubMed Central

Papoti, Daniel; Yen, Cecil Chern-Chyi; Mackel, Julie B.; Merkle, Hellmut; Silva, Afonso C.

2014-01-01

Functional Magnetic Resonance Imaging (fMRI) has established itself as the main research tool in neuroscience and brain cognitive research. The common marmoset (Callithrix jacchus) is a non-human primate model of increasing interest in biomedical research. However, commercial MRI coils for marmosets are not generally available. The present work describes the design and construction of a 4-channel receive-only surface RF coil array with excellent signal-to-noise ratio (SNR) specifically optimized for fMRI experiments in awake marmosets in response to somatosensory stimulation. The array was designed as part of a helmet-based head restraint system used to prevent motion during the scans. High SNR was obtained by building the coil array using a thin and flexible substrate glued to the inner surface of the restraint helmet, so as to minimize the distance between the array elements and the somatosensory cortex. Decoupling between coil elements was achieved by partial geometrical overlapping and by connecting them to home-built low input impedance preamplifiers. In vivo images show excellent coverage of the brain cortical surface with high sensitivity near the somatosensory cortex. Embedding the coil elements within the restraint helmet allowed fMRI data in response to somatosensory stimulation to be collected with high sensitivity and reproducibility in conscious, awake marmosets. PMID:23696219

Object permanence in adult common marmosets (Callithrix jacchus): not everything is an "A-not-B" error that seems to be one.

PubMed

Kis, Anna; Gácsi, Márta; Range, Friederike; Virányi, Zsófia

2012-01-01

In this paper, we describe a behaviour pattern similar to the "A-not-B" error found in human infants and young apes in a monkey species, the common marmosets (Callithrix jacchus). In contrast to the classical explanation, recently it has been suggested that the "A-not-B" error committed by human infants is at least partially due to misinterpretation of the hider's ostensively communicated object hiding actions as potential 'teaching' demonstrations during the A trials. We tested whether this so-called Natural Pedagogy hypothesis would account for the A-not-B error that marmosets commit in a standard object permanence task, but found no support for the hypothesis in this species. Alternatively, we present evidence that lower level mechanisms, such as attention and motivation, play an important role in committing the "A-not-B" error in marmosets. We argue that these simple mechanisms might contribute to the effect of undeveloped object representational skills in other species including young non-human primates that commit the A-not-B error.

Corticofugal modulation of time-domain processing of biosonar information in bats.

PubMed

Yan, J; Suga, N

1996-08-23

The Jamaican mustached bat has delay-tuned neurons in the inferior colliculus, medial geniculate body, and auditory cortex. The responses of these neurons to an echo are facilitated by a biosonar pulse emitted by the bat when the echo returns with a particular delay from a target located at a particular distance. Electrical stimulation of cortical delay-tuned neurons increases the delay-tuned responses of collicular neurons tuned to the same echo delay as the cortical neurons and decreases those of collicular neurons tuned to different echo delays. Cortical neurons improve information processing in the inferior colliculus by way of the corticocollicular projection.

An eye tracking system for monitoring face scanning patterns reveals the enhancing effect of oxytocin on eye contact in common marmosets.

PubMed

Kotani, Manato; Shimono, Kohei; Yoneyama, Toshihiro; Nakako, Tomokazu; Matsumoto, Kenji; Ogi, Yuji; Konoike, Naho; Nakamura, Katsuki; Ikeda, Kazuhito

2017-09-01

Eye tracking systems are used to investigate eyes position and gaze patterns presumed as eye contact in humans. Eye contact is a useful biomarker of social communication and known to be deficient in patients with autism spectrum disorders (ASDs). Interestingly, the same eye tracking systems have been used to directly compare face scanning patterns in some non-human primates to those in human. Thus, eye tracking is expected to be a useful translational technique for investigating not only social attention and visual interest, but also the effects of psychiatric drugs, such as oxytocin, a neuropeptide that regulates social behavior. In this study, we report on a newly established method for eye tracking in common marmosets as unique New World primates that, like humans, use eye contact as a mean of communication. Our investigation was aimed at characterizing these primates face scanning patterns and evaluating the effects of oxytocin on their eye contact behavior. We found that normal common marmosets spend more time viewing the eyes region in common marmoset's picture than the mouth region or a scrambled picture. In oxytocin experiment, the change in eyes/face ratio was significantly greater in the oxytocin group than in the vehicle group. Moreover, oxytocin-induced increase in the change in eyes/face ratio was completely blocked by the oxytocin receptor antagonist L-368,899. These results indicate that eye tracking in common marmosets may be useful for evaluating drug candidates targeting psychiatric conditions, especially ASDs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Positron emission tomography assessment of 8-OH-DPAT-mediated changes in an index of cerebral glucose metabolism in female marmosets

PubMed Central

Converse, Alexander K.; Aubert, Yves; Farhoud, Mohammed; Weichert, Jamey P.; Rowland, Ian J.; Ingrisano, Nicole M.; Allers, Kelly A.; Sommer, Bernd; Abbott, David H.

2013-01-01

As part of a larger experiment investigating serotonergic regulation of female marmoset sexual behavior, this study was designed to (1) advance methods for PET imaging of common marmoset monkey brain, (2) measure normalized FDG uptake as an index of local cerebral metabolic rates for glucose, and (3) study changes induced in this index of cerebral glucose metabolism by chronic treatment of female marmosets with a serotonin 1A receptor (5-HT1A) agonist. We hypothesized that chronic treatment with the 5-HT1A agonist 8-OH-DPAT would alter the glucose metabolism index in dorsal raphe (DR), medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus (VMH), and field CA1 of hippocampus. Eight adult ovariectomized female common marmosets (Callithrix jacchus) were studied with and without estradiol replacement. In a crossover design, each subject was treated daily with 8-OH-DPAT (0.1 mg/kg SC daily) or saline. After 42–49 days of treatment, the glucose metabolism radiotracer FDG was administered to each female immediately prior to 30 min of interaction with her male pairmate, after which the subject was anesthetized and imaged by PET. Whole brain normalized PET images were analyzed with anatomically defined regions of interest (ROI). Whole brain voxelwise mapping was also used to explore treatment effects and correlations between alterations in the glucose metabolism index and pairmate interactions. The rank order of normalized FDG uptake was VMH/mPOA>DR>mPFC/CA1 in both conditions. 8-OH-DPAT did not induce alterations in the glucose metabolism index in ROIs. Voxelwise mapping showed a significant reduction in normalized FDG uptake in response to 8-OH-DPAT in a cluster in medial occipital cortex as well as a significant correlation between increased rejection of mount attempts and reduced normalized FDG uptake in an overlapping cluster. In conclusion, PET imaging has been used to measure FDG uptake relative to whole

Binaural interaction in low-frequency neurons in inferior colliculus of the cat. I. Effects of long interaural delays, intensity, and repetition rate on interaural delay function.

PubMed

Kuwada, S; Yin, T C

1983-10-01

Detailed, quantitative studies were made of the interaural phase sensitivity of 197 neurons with low best frequency in the inferior colliculus (IC) of the barbiturate-anesthetized cat. We analyzed the responses of single cells to interaural delays in which tone bursts were delivered to the two ears via sealed earphones and the onset of the tone to one ear with respect to the other was varied. For most (80%) cells the discharge rate is a cyclic function of interaural delay at a period corresponding to that of the stimulating frequency. The cyclic nature of the interaural delay curve indicates that these cells are sensitive to the interaural phase difference. These cells are distributed throughout the low-frequency zone of the IC, but they are less numerous in the medial and caudal zones. Cells with a wide variety of response patterns will exhibit interaural phase sensitivities at stimulating frequencies up to 3,100 Hz, although above 2,500 Hz the number of such cells decrease markedly. Using dichotic stimuli we could study the cell's sensitivity to the onset delay and interaural phase independently. The large majority of IC cells respond only to changes in interaural phase, with no sensitivity to the onset delay. However, a small number (7%) of cells exhibit a sensitivity to the onset delay as well as to the interaural phase disparity, and most of these cells show an onset response. The effects of changing the stimulus intensity equally to both ears or of changing the interaural intensity difference on the mean interaural phase were studied. While some neurons are not affected by level changes, others exhibit systematic phase shifts for both average and interaural intensity variations, and there is a continuous distribution of sensitivities between these extremes. A few cells also showed systematic changes in the shape of the interaural delay curves as a function of interaural intensity difference, especially at very long delays. These shifts can be interpreted as a

Sleep and Alertness Management I: Pharmacokinetics of Hypnotics and Alertness Enhancers in Marmoset Monkeys (slaap- en alertheidsmanagement I: farmacokinetiek van slaap- en alertheidsverhogendemiddelen in marmosetapen)

DTIC Science & Technology

2006-10-01

drugs. However, if these drugs are to be used in a novel animal model setting ( the marmoset), pharmacokinetics will be different and need to be re... pharmacokinetics are usually well- known for approved drugs. However, if these drugs are to be used in a novel animal model setting ( the marmoset...an adsorption phase and elimination phase. In Figure 7 the combined data of 30 mg/kg and repeated caffeine dosing was shown. Toxicokinetic parameters

Spontaneous mediastinal myeloid sarcoma in a common marmoset (Callithrix jacchus) and review of the veterinary literature

PubMed Central

Morosco, Danielle T.; Cline, Curtis R.; Owston, Michael A.; Kumar, Shyamesh; Dick, Edward J.

2017-01-01

Background Myeloid sarcoma is a rare manifestation of myeloproliferative disorder defined as an extramedullary mass composed of myeloid precursor cells. A 9-month old, female, common marmoset (Callithrix jacchus) had increased respiratory effort. Methods A complete necropsy with histology and immunohistochemistry was performed. Results The thymus was replaced by a firm, grey-tan mass with a faint green tint, filling over 50% of the thoracic cavity. Sheets of granulocytes, lymphoid cells, nucleated erythrocytes, megakaryocytes, and hematopoietic precursors of indeterminate cell lineage replaced the thymus, perithymic connective tissue, mediastinal adipose tissues, epicardium, and much of the myocardium. The cells demonstrated diffuse strong cytoplasmic immunoreactivity for lysozyme, and strong, multifocal membranous immunoreactivity for CD117. Conclusion We report the first case of a myeloid sarcoma in a common marmoset (Callithrix jacchus), similar to reported human cases of mediastinal myeloid sarcoma, and present a review of myeloproliferative diseases from the veterinary literature. PMID:28145579

How many pygmy marmoset (Cebuella Gray, 1870) species are there? A taxonomic re-appraisal based on new molecular evidence.

PubMed

Boubli, Jean P; da Silva, Maria N F; Rylands, Anthony B; Nash, Stephen D; Bertuol, Fabrício; Nunes, Mário; Mittermeier, Russell A; Byrne, Hazel; Silva, Felipe E; Röhe, Fábio; Sampaio, Iracilda; Schneider, Horacio; Farias, Izeni P; Hrbek, Tomas

2018-03-01

The pygmy marmoset, Cebuella pygmaea, the smallest of the New World monkeys, has one of the largest geographical distributions of the Amazonian primates. Two forms have been recognized: Cebuella pygmaea pygmaea (Spix, 1823), and C. p. niveiventris Lönnberg, 1940. In this study, we investigated if the separation of pygmy marmosets into these two clades can be corroborated by molecular data. We also examine and compare coloration of the pelage in light of the new molecular results. We analyzed the mtDNA cytochrome b gene and, for the first time for any Neotropical primate, we used a reduced representation genome sequencing approach (ddRADseq) to obtain data for recently collected, geographically representative samples from the Rio Japurá, a northern tributary of the Rio Solimões and from the Javarí, Jutaí, Juruá, Madeira and Purus river basins, all tributaries south of the Solimões. We estimated phylogenies and diversification times under both maximum likelihood and Bayesian inference criteria. Our analysis showed two highly supported clades, with intraclade divergences much smaller than interclade divergences, indicating two species of Cebuella: one from the Rio Japurá and one to the south of Solimões. The interpretation of our results in light of the current taxonomy is not trivial however. Lönnberg stated that the type of Spix's pygmy marmoset (type locality 'near Tabatinga') was obtained from the south of the Solimões, and his description of the distinct niveiventris from Lago Ipixuna, south of the Solimões and several hundred kilometres east of Tabatinga, was based on a comparison with specimens that he determined as typical pygmaea that were from the upper Rio Juruá (south of the Solimões). As such it remains uncertain whether the name pygmaea should be applicable to the pygmy marmosets north of the Rio Solimões (Tabatinga type locality) or south (near Tabatinga but across the Solimões). Finally, our analysis of pelage coloration revealed three

ELECTROPHYSIOLOGICAL AND MORPHOLOGICAL EVIDENCE FOR A DIAMETER-BASED INNERVATION PATTERN OF THE SUPERIOR COLLICULUS (JOURNAL VERSION)

EPA Science Inventory

Neurophysiological and morphological techniques were used to describe changes in the optic tract and superior colliculus (SC) in response to monocular enucleation. Long-Evans, male, (250g) rats were implanted with chronic bipolar stimulating electrodes located in the optic chiasm...

The effect of simultaneous negative and positive defocus on eye growth and development of refractive state in marmosets.

PubMed

Benavente-Perez, Alexandra; Nour, Ann; Troilo, David

2012-09-21

We evaluated the effect of imposing negative and positive defocus simultaneously on the eye growth and refractive state of the common marmoset, a New World primate that compensates for either negative and positive defocus when they are imposed individually. Ten marmosets were reared with multizone contact lenses of alternating powers (-5 diopters [D]/+5 D), 50:50 ratio for average pupil of 2.80 mm over the right eye (experimental) and plano over the fellow eye (control) from 10 to 12 weeks. The effects on refraction (mean spherical equivalent [MSE]) and vitreous chamber depth (VC) were measured and compared to untreated, and -5 D and +5 D single vision contact lens-reared marmosets. Over the course of the treatment, pupil diameters ranged from 2.26 to 2.76 mm, leading to 1.5 times greater exposure to negative than positive power zones. Despite this, at different intervals during treatment, treated eyes were on average relatively more hyperopic and smaller than controls (experimental-control [exp-con] mean MSE ± SE +1.44 ± 0.45 D, mean VC ± SE -0.05 ± 0.02 mm) and the effects were similar to those in marmosets raised on +5 D single vision contact lenses (exp-con mean MSE ± SE +1.62 ± 0.44 D. mean VC ± SE -0.06 ± 0.03 mm). Six weeks into treatment, the interocular growth rates in multizone animals were already lower than in -5 D-treated animals (multizone -1.0 ± 0.1 μm/day, -5 D +2.1 ± 0.9 μm/day) and did not change significantly throughout treatment. Imposing hyperopic and myopic defocus simultaneously using concentric contact lenses resulted in relatively smaller and less myopic eyes, despite treated eyes being exposed to a greater percentage of negative defocus. Exposing the retina to combined dioptric powers with multifocal lenses that include positive defocus might be an effective treatment to control myopia development or progression.

Effects of lurasidone on ketamine-induced joint visual attention dysfunction as a possible disease model of autism spectrum disorders in common marmosets.

PubMed

Nakako, Tomokazu; Murai, Takeshi; Ikejiri, Masaru; Hashimoto, Takashi; Kotani, Manato; Matsumoto, Kenji; Manabe, Shoji; Ogi, Yuji; Konoike, Naho; Nakamura, Katsuki; Ikeda, Kazuhito

2014-11-01

Infants with autism have difficulties performing joint visual attention (JVA), defined as following another person's pointing gesture and gaze. Some non-human primates (NHPs) can also perform JVA. Most preclinical research on autism spectrum disorders (ASD) has used rodents as animal models of this social interaction disorder. However, models using rodents fail to capture the complexity of social interactions that are disrupted in ASD. Therefore, JVA impairment in NHPs might be a more useful model of ASD. The aim of this study was to develop an appropriate and convenient ASD model with common marmosets. We first tested whether marmosets were capable of performing JVA. Subsequently, we administered ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, to induce JVA impairment and investigated the effects of lurasidone, a newer antipsychotic agent, on the JVA impairments. An apparatus was constructed using 4 white boxes, which were attached to the corners of a frame. All boxes had a hinged door, and marmosets could easily obtain a reward by pushing the door. An experimenter pointed and gazed at the boxes to inform the marmosets which box contained the reward. Their behavior was scored according to the number of incorrect choices. The JVA score was significantly higher in the cued vs. uncued tasks. Ketamine significantly decreased the JVA score, but lurasidone significantly reversed this effect. These findings suggest that this experimental system could be a useful animal model of neuropsychiatric disorders characterized by NMDA-receptor signaling, including ASD, and that lurasidone might be effective for some aspects of ASD. Copyright © 2014 Elsevier B.V. All rights reserved.

Gestational cortisol and social play shape development of marmosets' HPA functioning and behavioral responses to stressors.

PubMed

Mustoe, Aaryn C; Taylor, Jack H; Birnie, Andrew K; Huffman, Michelle C; French, Jeffrey A

2014-09-01

Both gestational cortisol exposure (GCE) and variability in postnatal environments can shape the later-life behavioral and endocrine outcomes of the hypothalamic-pituitary-adrenal (HPA) axis. We examined the influence of GCE and social play on HPA functioning in developing marmosets. Maternal urinary cortisol samples were collected across pregnancy to determine GCE for 28 marmoset offspring (19 litters). We administered a social separation stressor to offspring at 6, 12, and 18 months of age, during which we collected urinary cortisol samples and behavioral observations. Increased GCE was associated with increased basal cortisol levels and cortisol reactivity, but the strength of this relationship decreased across age. Increased social play was associated with decreased basal cortisol levels and a marginally greater reduction in cortisol reactivity as offspring aged, regardless of offspring GCE. Thus, GCE is associated with HPA functioning, but socially enriching postnatal environments can alter the effects associated with increased fetal exposure to glucocorticoids. © 2014 Wiley Periodicals, Inc.

Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities.

PubMed

Seferovic, Maxim; Martín, Claudia Sánchez-San; Tardif, Suzette D; Rutherford, Julienne; Castro, Eumenia C C; Li, Tony; Hodara, Vida L; Parodi, Laura M; Giavedoni, Luis; Layne-Colon, Donna; Tamhankar, Manasi; Yagi, Shigeo; Martyn, Calla; Reyes, Kevin; Suter, Melissa A; Aagaard, Kjersti M; Chiu, Charles Y; Patterson, Jean L

2018-05-01

During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.

Calibration and validation of a physiologically based model for soman intoxication in the rat, marmoset, guinea pig and pig.

PubMed

Chen, Kaizhen; Seng, Kok-Yong

2012-09-01

A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model has been developed for low, medium and high levels of soman intoxication in the rat, marmoset, guinea pig and pig. The primary objective of this model was to describe the pharmacokinetics of soman after intravenous, intramuscular and subcutaneous administration in the rat, marmoset, guinea pig, and pig as well as its subsequent pharmacodynamic effects on blood acetylcholinesterase (AChE) levels, relating dosimetry to physiological response. The reactions modelled in each physiologically realistic compartment are: (1) partitioning of C(±)P(±) soman from the blood into the tissue; (2) inhibition of AChE and carboxylesterase (CaE) by soman; (3) elimination of soman by enzymatic hydrolysis; (4) de novo synthesis and degradation of AChE and CaE; and (5) aging of AChE-soman and CaE-soman complexes. The model was first calibrated for the rat, then extrapolated for validation in the marmoset, guinea pig and pig. Adequate fits to experimental data on the time course of soman pharmacokinetics and AChE inhibition were achieved in the mammalian models. In conclusion, the present model adequately predicts the dose-response relationship resulting from soman intoxication and can potentially be applied to predict soman pharmacokinetics and pharmacodynamics in other species, including human. Copyright © 2011 John Wiley & Sons, Ltd.

Large-scale brain networks in the awake, truly resting marmoset monkey.

PubMed

Belcher, Annabelle M; Yen, Cecil C; Stepp, Haley; Gu, Hong; Lu, Hanbing; Yang, Yihong; Silva, Afonso C; Stein, Elliot A

2013-10-16

Resting-state functional MRI is a powerful tool that is increasingly used as a noninvasive method for investigating whole-brain circuitry and holds great potential as a possible diagnostic for disease. Despite this potential, few resting-state studies have used animal models (of which nonhuman primates represent our best opportunity of understanding complex human neuropsychiatric disease), and no work has characterized networks in awake, truly resting animals. Here we present results from a small New World monkey that allows for the characterization of resting-state networks in the awake state. Six adult common marmosets (Callithrix jacchus) were acclimated to light, comfortable restraint using individualized helmets. Following behavioral training, resting BOLD data were acquired during eight consecutive 10 min scans for each conscious subject. Group independent component analysis revealed 12 brain networks that overlap substantially with known anatomically constrained circuits seen in the awake human. Specifically, we found eight sensory and "lower-order" networks (four visual, two somatomotor, one cerebellar, and one caudate-putamen network), and four "higher-order" association networks (one default mode-like network, one orbitofrontal, one frontopolar, and one network resembling the human salience network). In addition to their functional relevance, these network patterns bear great correspondence to those previously described in awake humans. This first-of-its-kind report in an awake New World nonhuman primate provides a platform for mechanistic neurobiological examination for existing disease models established in the marmoset.

Production and Perception of Sex Differences in Vocalizations of Wied’s Black-Tufted-Ear Marmosets (Callithrix kuhlii)

PubMed Central

Smith, Adam S.; Birnie, Andrew K.; Lane, Kent R.; French, Jeffrey A.

2010-01-01

Males and females from many species produce distinct acoustic variations of functionally identical call types. Social behavior may be primed by sex-specific variation in acoustic features of calls. We present a series of acoustic analyses and playback experiments as methods for investigating this subject. Acoustic parameters of phee calls produced by Wied’s black-tufted-ear marmosets (Callithrix kuhlii) were analyzed for sex differences. Discriminant function analyses showed that calls contained sufficient acoustic variation to predict the sex of the caller. Several frequency variables differed significantly between the sexes. Natural and synthesized calls were presented to male–female pairs. Calls elicited differential behavioral responses based on the sex of the caller. Marmosets became significantly more vigilant following the playback of male phee calls (both natural and synthetic) than following female phee calls. In a second playback experiment, synthesized calls were modified by independently manipulating three parameters that were known to differ between the sexes (low-, peak-, and end-frequency). When end-frequency-modified calls were presented, responsiveness was differentiable by sex of caller but did not differ from responses to natural calls. This suggests that marmosets did not use end-frequency to determine the sex of the caller. Manipulation of peak-and low-frequency parameters eliminated the discrete behavioral responses to male and female calls. Together, these parameters may be important features that encode for the sex-specific signal. Recognition of sex by acoustic cues seems to be a multivariate process that depends on the congruency of acoustic features. PMID:19090554

Glutamine/glutamate (Glx) concentration in prefrontal cortex predicts reversal learning performance in the marmoset.

PubMed

Lacreuse, Agnès; Moore, Constance M; LaClair, Matthew; Payne, Laurellee; King, Jean A

2018-07-02

This study used Magnetic Resonance Spectroscopy (MRS) to identify potential neurometabolitic markers of cognitive performance in male (n = 7) and female (n = 8) middle-aged (∼5 years old) common marmosets (Callithrix jacchus). Anesthetized marmosets were scanned with a 4.7 T/40 cm horizontal magnet equipped with 450 mT/m magnetic field gradients and a 20 G/cm magnetic field gradient insert, within 3 months of completing the CANTAB serial Reversal Learning task. Neurometabolite concentrations of N-Acetyl Asparate, Myo-Inositol, Choline, Phosphocreatine + creatine, Glutamate and Glutamine were acquired from a 3 mm 3 voxel positioned in the Prefrontal Cortex (PFC). Males acquired the reversals (but not simple discriminations) faster than the females. Higher PFC Glx (glutamate + glutamine) concentration was associated with faster acquisition of the reversals. Interestingly, the correlation between cognitive performance and Glx was significant in males, but not in females. These results suggest that MRS is a useful tool to identify biochemical markers of cognitive performance in the healthy nonhuman primate brain and that biological sex modulates the relationship between neurochemical composition and cognition. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of spiral acquisition variants for functional imaging of human superior colliculus at 3T field strength.

PubMed

Singh, Vimal; Pfeuffer, Josef; Zhao, Tiejun; Ress, David

2018-04-01

High-resolution functional magnetic resonance imaging of human subcortical brain structures is challenging because of their deep location in the cranium, and their comparatively weak blood oxygen level dependent responses to strong stimuli. Magnetic resonance imaging data for subcortical brain regions exhibit both low signal-to-noise ratio and low functional contrast-to-noise ratio. To overcome these challenges, this work evaluates the use of dual-echo spiral variants that combine outward and inward trajectories. Specifically, in-in, in-out, and out-out combinations are evaluated. For completeness, single-echo spiral-in and parallel-receive-accelerated echo-planar-imaging sequences are also evaluated. Sequence evaluation was based on comparison of functional contrast-to-noise ratio within retinotopically predefined regions of interest. Superior colliculus was chosen as sample subcortical brain region because it exhibits a strong visual response. All sequences were compared relative to a single-echo spiral-out trajectory to establish a within-session reference. In superior colliculus, the dual-echo out-out outperformed the reference trajectory by 55% in contrast-to-noise ratio, while all other trajectories had performance similar to the reference. The sequences were also compared in early visual cortex. Here, both dual-echo spiral out-out and in-out outperformed the reference by ∼25%. Dual-echo spiral variants offer improved contrast-to-noise ratio performance for high-resolution imaging for both superior colliculus and cortex. Magn Reson Med 79:1931-1940, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Multiple vaccine and pyridostigmine bromide interactions in the common marmoset Callithrix jacchus: immunological and endocrinological effects.

PubMed

Hornby, Rebecca J; Pearce, Peter C; Bowditch, Andrew P; Scott, Leah; Griffiths, Gareth D

2006-12-05

Following active service during the 1990/1991 Gulf Conflict, a number of UK and US veterans presented with a diverse range of symptoms, collectively known as Gulf Veterans Illnesses (GVI). The administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (PB), given to Armed Forces personnel during the Gulf Conflict has been implicated as a possible factor in the aetiology of these illnesses. The possibility that adverse health effects may result from the administration of these vaccines (anthrax, pertussis, plague, yellow fever, polio, typhoid, tetanus, hepatitis B, meningococcal meningitis and cholera) and/or PB, have been investigated over an eighteen month period, in a non-human primate model, the common marmoset. This study reports immunological indices, including leukocyte phenotypes, intracellular cytokines IFN-gamma and IL-4 and antibody responses against vaccine antigens. Using human isotyping reagents previously shown to cross react with marmoset immunoglobulins (ibid) it was shown that marmosets responded strongly against anthrax PA and pertussis and weakly against killed whole cell plague, cholera and typhoid. At the end of the study the immune response to a previously unseen T-cell dependent antigen, keyhole limpet haemocyanin (KLH), was examined in order to determine whether immune function had been compromised by the compounds administered. Statistically equivalent, robust antibody responses were measured against KLH in all treatment groups indicating that the immune system had not been compromised by any of the treatments. In addition, urinary cortisol was measured at key points throughout the study as an index of physiological stress which may have been induced by the treatments. There were no effects of treatment on urinary cortisol secretion. With respect to the other immunological indices measured, there were no statistical differences between the treatment groups during the period of the study.

Fetal sulcation and gyrification in common marmosets (Callithrix jacchus) obtained by ex vivo magnetic resonance imaging.

PubMed

Sawada, K; Hikishima, K; Murayama, A Y; Okano, H J; Sasaki, E; Okano, H

2014-01-17

The present study characterized fetal sulcation patterns and gyrification in the cerebrum of the New World monkey group, common marmosets, using a 3D T2-weighted high-resolution anatomical magnetic resonance imaging (MRI) sequence from the fixed brain at 7-tesla ex vivo. Fetal sulcation in the marmoset cerebrum began to indent the lateral fissure and hippocampal sulcus in gestational week (GW) 12, and then the following sulci emerged: the callosal and calcarine sulci on GW 15; the superior temporal sulcus on GW 17; and the circular and occipitotemporal sulci on GW 18. The degree of cortical convolution was evaluated quantitatively based on 2D MRI slices by the gyrification index (GI) and based on 3D MRI data by sulcation index (SI). Both the mean GI and SI increased from GW 16, and were closely correlated with the cortical volume and the cortical surface area during fetal periods (their correlation coefficients marked more than 0.95). After birth, both the mean GI and SI decreased slightly by 2years of age, whereas the cortical volume and surface area continuously increased. Notably, histological analysis showed that the outer subventricular zone (oSVZ) in non-sulcal regions was thicker than that in the presumptive calcarine sulcal region on GW 13, preceding the infolding of the calcarine sulcus. The present results showed definite sulcal infolding on the cerebral cortical surface of the marmosets, with similar pattern and sequence of their emergences to other higher-order primates such as macaques and humans. Differential expansion of the oSVZ may be involved in gyral convolution and sulcal infolding in the developing cerebrum. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Cutting costs in response to predatory threat by Geoffroy's marmosets (Callithrix geoffroyi).

PubMed

Caine, N G

1998-01-01

Ideally, prey should respond to their predators efficiently, without over- or underreacting to the threat. This may be particularly important for small-bodied species for whom metabolic demands are high and predatory risk is great. In the current study, two family groups of Callithrix geoffroyi living outside in a rural setting at the Center for Reproduction of Endangered Species, San Diego Wild Animal Park, were observed before, during, and after ten presentations of a great horned owl model. The owl was mounted on a post on a nearby hillside, simulating a situation in which a real but nonimminent threat is posed. As controls, a model of a crow and a cloth bag were also presented, each for ten trials. During the 10 min presentations of the owl, rates of play and foraging decreased, and rates of locomotion and vigilant looking increased from baseline rates. Data on occupation of the best viewing area suggest that the marmosets shared the job of monitoring a potential threat. After the owl was removed, behavior quickly returned to baseline rates, with the exception of looking at the place where the owl had been, and play. Neither the bag nor the crow generated significant differences from the baseline condition that preceded it. Marmosets may reduce the costs of antipredator behavior by appropriately assessing the degree of risk and by quickly resuming important activities once a potential threat has passed.

Chronic stress impairs acoustic conditioning more than visual conditioning in rats: morphological and behavioural evidence.

PubMed

Dagnino-Subiabre, A; Terreros, G; Carmona-Fontaine, C; Zepeda, R; Orellana, J A; Díaz-Véliz, G; Mora, S; Aboitiz, F

2005-01-01

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.

Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

PubMed

Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

2015-01-01

Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease

PubMed Central

Mucker, Eric M.; Chapman, Jennifer; Huzella, Louis M.; Huggins, John W.; Shamblin, Joshua; Robinson, Camenzind G.; Hensley, Lisa E.

2015-01-01

Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox. PMID:26147658

Cognitive impairment in a young marmoset reveals lateral ventriculomegaly and a mild hippocampal atrophy: a case report

PubMed Central

Sadoun, A.; Strelnikov, K.; Bonté, E.; Fonta, C.; Girard, P.

2015-01-01

The number of studies that use the common marmoset (Callithrix jacchus) in various fields of neurosciences is increasing dramatically. In general, animals enter the study when their health status is considered satisfactory on the basis of classical clinical investigations. In behavioral studies, variations of score between individuals are frequently observed, some of them being considered as poor performers or outliers. Experimenters rarely consider the fact that it could be related to some brain anomaly. This raises the important issue of the reliability of such classical behavioral approaches without using complementary imaging, especially in animals lacking striking external clinical signs. Here we report the case of a young marmoset which presented a set of cognitive impairments in two different tasks compared to other age-matched animals. Brain imaging revealed a patent right lateral ventricular enlargement with a mild hippocampal atrophy. This abnormality could explain the cognitive impairments of this animal. Such a case points to the importance of complementing behavioral studies by imaging explorations to avoid experimental bias. PMID:26527211

Protection by pyridostigmine bromide of marmoset hemi-diaphragm acetylcholinesterase activity after soman exposure.

PubMed

Haigh, Julian R; Adler, Michael; Apland, James P; Deshpande, Sharad S; Barham, Charles B; Desmond, Patrick; Koplovitz, Irwin; Lenz, David E; Gordon, Richard K

2010-09-06

Pyridostigmine bromide (PB) was approved by the U.S. Food and Drug Administration (FDA) in 2003 as a pretreatment in humans against the lethal effects of the irreversible nerve agent soman (GD). Organophosphate (OP) chemical warfare agents such as GD exert their toxic effects by inhibiting acetylcholinesterase (AChE) from terminating the action of acetylcholine at postsynaptic sites in cholinergic nerve terminals (including crucial peripheral muscle such as diaphragm). As part of the post-marketing approval of PB, the FDA required (under 21CFR314, the "two animal rule") the study of a non-human primate model (the common marmoset Callithrix jacchus jacchus) to demonstrate increased survival against lethal GD poisoning, and protection of physiological hemi-diaphragm function after PB pretreatment and subsequent GD exposure. Marmosets (male and female) were placed in the following experimental groups: (i) control (saline pretreatment only), (ii) low dose PB (12.5 microg/kg), or (iii) high dose (39.5 microg/kg) PB. Thirty minutes after the PB dose, animals were challenged with either saline (control) or soman (GD, 45 microg/kg), followed 1 min later by atropine (2mg/kg) and 2-PAM (25mg/kg). After a further 16 min, animals were euthanized and the complete diaphragm removed; the right hemi-diaphragm was frozen immediately at -80 degrees C, and the left hemi-diaphragm was placed in a tissue bath for 4h (to allow for decarbamylation to occur), then frozen. AChE activities were determined using the automated WRAIR cholinesterase assay. Blood samples were collected for AChE activities prior to PB, before GD challenge, and after sacrifice. RBC-AChE was inhibited by approximately 18% and 50% at the low and high doses of PB, respectively, compared to control (baseline) activity. In the absence of PB pretreatment, the inhibition of RBC-AChE by GD was 98%. The recovery of hemi-diaphragm AChE activity after the 4h wash period (decarbamylation) was approximately 8% and 17%, at the

Preimplantation development of somatic cell cloned embryos in the common marmoset (Callithrix jacchus).

PubMed

Sotomaru, Yusuke; Hirakawa, Reiko; Shimada, Akiko; Shiozawa, Seiji; Sugawara, Ayako; Oiwa, Ryo; Nobukiyo, Asako; Okano, Hideyuki; Tamaoki, Norikazu; Nomura, Tatsuji; Hiyama, Eiso; Sasaki, Erika

2009-12-01

The somatic cell nuclear transfer technique has been applied to various mammals to produce cloned animals; however, a standardized method is not applicable to all species. We aimed here to develop optimum procedures for somatic cell cloning in nonhuman primates, using common marmosets. First, we confirmed that parthenogenetic activation of in vitro matured oocytes was successfully induced by electrical stimulation (three cycles of 150 V/mm, 50 microsec x 2, 20 min intervals), and this condition was applied to the egg activation procedure in the subsequent experiments. Next, nuclear transfer to recipient enucleated oocytes was performed 1 h before, immediately after, or 1 h after egg activation treatment. The highest developmental rate was observed when nuclear transfer was performed 1 h before activation, but none of the cloned embryos developed beyond the eight-cell stage. To investigate the causes of the low developmental potential of cloned embryos, a study was performed to determine whether the presence of metaphase II (MII) chromosome in recipient ooplasm has an effect on developmental potential. As a result, only tetraploid cloned embryos produced by transferring a donor cell into a recipient bearing the MII chromosome developed into blastocysts (66.7%). In contrast, neither parthenogenetic embryos nor cloned embryos (whether diploid or tetraploid) produced using enucleated oocytes developed past the eight-cell stage. These results suggest that MII chromosome, or cytoplasm proximal to the MII chromosome, plays a major role in the development of cloned embryos in common marmosets.

Prenatal programming of metabolic syndrome in the common marmoset is associated with increased expression of 11beta-hydroxysteroid dehydrogenase type 1.

PubMed

Nyirenda, Moffat J; Carter, Roderick; Tang, Justin I; de Vries, Annick; Schlumbohm, Christina; Hillier, Stephen G; Streit, Frank; Oellerich, Michael; Armstrong, Victor W; Fuchs, Eberhard; Seckl, Jonathan R

2009-12-01

Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which amplifies local tissue glucocorticoid concentrations. The reasons for this 11beta-HSD1 dysregulation are unknown. Here, we tested whether 11beta-HSD1 expression, like the metabolic syndrome, is "programmed" by prenatal environmental events in a nonhuman primate model, the common marmoset monkey. We used a "fetal programming" paradigm where brief antenatal exposure to glucocorticoids leads to the metabolic syndrome in the offspring. Pregnant marmosets were given the synthetic glucocorticoid dexamethasone orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11beta-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age. Prenatal dexamethasone administration, selectively during late gestation, resulted in early and persistent elevations in 11beta-HSD1 mRNA expression and activity in the liver, pancreas, and subcutaneous-but not visceral-fat. The increase in 11beta-HSD1 occurred before animals developed obesity or overt features of the metabolic syndrome. In contrast to rodents, in utero dexamethasone exposure did not alter glucocorticoid receptor expression in metabolic tissues in marmosets. These data suggest that long-term upregulation of 11beta-HSD1 in metabolically active tissues may follow prenatal "stress" hormone exposure and indicates a novel mechanism for fetal origins of adult obesity and the metabolic syndrome.

A longitudinal analysis of the effects of age on the blood plasma metabolome in the common marmoset, Callithrix jacchus

PubMed Central

Hoffman, Jessica M.; Tran, ViLinh; Wachtman, Lynn M.; Green, Cara L.; Jones, Dean P.; Promislow, Daniel E.L.

2016-01-01

Primates tend to be long-lived for their size with humans being the longest lived of all primates. There are compelling reasons to understand the underlying age-related processes that shape human lifespan. But the very fact of our long lifespan that makes it so compelling, also makes it especially difficult to study. Thus, in studies of aging, researchers have turned to non-human primate models, including chimpanzees, baboons, and rhesus macaques. More recently, the common marmoset, Callithrix jacchus, has been recognized as a particularly valuable model in studies of aging, given its small size, ease of housing in captivity, and relatively short lifespan. However, little is known about the physiological changes that occur as marmosets age. To begin to fill in this gap, we utilized high sensitivity metabolomics to define the longitudinal biochemical changes associated with age in the common marmoset. We measured 2104 metabolites from blood plasma at three separate time points over a 17-month period, and we completed both a cross-sectional and longitudinal analysis of the metabolome. We discovered hundreds of metabolites associated with age and body weight in both male and female animals. Our longitudinal analysis identified age-associated metabolic pathways that were not found in our cross-sectional analysis. Pathways enriched for age-associated metabolites included tryptophan, nucleotide, and xenobiotic metabolism, suggesting these biochemical pathways might play an important role in the basic mechanisms of aging in primates. Moreover, we found that many metabolic pathways associated with age were sex specific. Our work illustrates the power of longitudinal approaches, even in a short time frame, to discover novel biochemical changes that occur with age. PMID:26805607

An Epstein–Barr-related herpesvirus from marmoset lymphomas

PubMed Central

Cho, Young-Gyu; Ramer, Jan; Rivailler, Pierre; Quink, Carol; Garber, Richard L.; Beier, David R.; Wang, Fred

2001-01-01

Epstein–Barr virus (EBV) is implicated in the development of human B cell lymphomas and carcinomas. Although related oncogenic herpesviruses were believed to be endemic only in Old World primate species, we now find these viruses to be endemic in New World primates. We have isolated a transforming, EBV-related virus from spontaneous B cell lymphomas of common marmosets (Callithrix jacchus). Sequencing of two-thirds of the genome reveals considerable divergence from the genomes of EBV and Old World primate EBV-related viruses, including differences in genes important for virus-induced cell growth transformation and pathogenesis. DNA related to the C. jacchus herpesvirus is frequently detected in squirrel monkey peripheral blood lymphocytes, indicating that persistent infection with EBV-related viruses is prevalent in both New World primate families. Understanding how these more divergent EBV-related viruses achieve similar biologic outcomes in their natural host is likely to provide important insights into EBV infection, B cell growth transformation, and oncogenesis. PMID:11158621

Precise Motor Control Enables Rapid Flexibility in Vocal Behavior of Marmoset Monkeys.

PubMed

Pomberger, Thomas; Risueno-Segovia, Cristina; Löschner, Julia; Hage, Steffen R

2018-03-05

Investigating the evolution of human speech is difficult and controversial because human speech surpasses nonhuman primate vocal communication in scope and flexibility [1-3]. Monkey vocalizations have been assumed to be largely innate, highly affective, and stereotyped for over 50 years [4, 5]. Recently, this perception has dramatically changed. Current studies have revealed distinct learning mechanisms during vocal development [6-8] and vocal flexibility, allowing monkeys to cognitively control when [9, 10], where [11], and what to vocalize [10, 12, 13]. However, specific call features (e.g., duration, frequency) remain surprisingly robust and stable in adult monkeys, resulting in rather stereotyped and discrete call patterns [14]. Additionally, monkeys seem to be unable to modulate their acoustic call structure under reinforced conditions beyond natural constraints [15, 16]. Behavioral experiments have shown that monkeys can stop sequences of calls immediately after acoustic perturbation but cannot interrupt ongoing vocalizations, suggesting that calls consist of single impartible pulses [17, 18]. Using acoustic perturbation triggered by the vocal behavior itself and quantitative measures of resulting vocal adjustments, we show that marmoset monkeys are capable of producing calls with durations beyond the natural boundaries of their repertoire by interrupting ongoing vocalizations rapidly after perturbation onset. Our results indicate that marmosets are capable of interrupting vocalizations only at periodic time points throughout calls, further supported by the occurrence of periodically segmented phees. These ideas overturn decades-old concepts on primate vocal pattern generation, indicating that vocalizations do not consist of one discrete call pattern but are built of many sequentially uttered units, like human speech. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The different clinical effects of anti-BLyS, anti-APRIL and anti-CD20 antibodies point at a critical pathogenic role of γ-herpesvirus infected B cells in the marmoset EAE model.

PubMed

Anwar Jagessar, S; Fagrouch, Zahra; Heijmans, Nicole; Bauer, Jan; Laman, Jon D; Oh, Luke; Migone, Thi; Verschoor, Ernst J; 't Hart, Bert A

2013-06-01

The robust and rapid clinical effect of depleting anti-CD20 monoclonal antibodies (mAb) in multiple sclerosis (MS) demonstrates a critical pathogenic contribution of B cells. The clinical effect of anti-CD20 mAb has been replicated in a relevant preclinical MS model, experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys (Callithrix jacchus). By contrast, treatment with mAbs against two essential cytokines in B cell activation growth and survival, i.e. BlyS/BAFF and APRIL, was only partially effective. All three mAbs induced depletion of CD20+ B cells from the circulation, albeit with different kinetics and based on distinct mechanisms of action. In the current study we analyzed whether the different clinical effect of anti-CD20 mAb or the anti-BLyS and anti-APRIL mAbs is due to different depletion of B cells infected with the EBV of marmosets, CalHV3. Employing a novel PCR-based assay, half of the colony of group-housed marmosets was tested positive for CalHV3 DNA in secondary lymphoid organs. The same prevalence was observed in placebo-treated monkeys. In marmosets treated with anti-CD20 mAb the load of CalHV3 DNA in lymphoid organs was substantially reduced, while this was not observed in the monkeys treated with anti-BLyS or anti-APRIL mAbs. To examine the pathogenic role of virus-transformed B cells, we infused EBV-transformed B lymphoblastic cell (BLC) lines presenting the immunodominant MOG34-56 peptide. We observed in the recipients of MOG34-56 pulsed BLC, but not in their fraternal siblings infused with non-pulsed BLC, activation of anti-MOG34-56 T cells and meningeal inflammation. Collectively, the data show that among CD20+ B cells, the herpesvirus-transformed subset has a particularly important pathogenic role in the marmoset EAE model.

Marmoset monkeys evaluate third-party reciprocity.

PubMed

Kawai, Nobuyuki; Yasue, Miyuki; Banno, Taku; Ichinohe, Noritaka

2014-05-01

Many non-human primates have been observed to reciprocate and to understand reciprocity in one-to-one social exchanges. A recent study demonstrated that capuchin monkeys are sensitive to both third-party reciprocity and violation of reciprocity; however, whether this sensitivity is a function of general intelligence, evidenced by their larger brain size relative to other primates, remains unclear. We hypothesized that highly pro-social primates, even with a relatively smaller brain, would be sensitive to others' reciprocity. Here, we show that common marmosets discriminated between human actors who reciprocated in social exchanges with others and those who did not. Monkeys accepted rewards less frequently from non-reciprocators than they did from reciprocators when the non-reciprocators had retained all food items, but they accepted rewards from both actors equally when they had observed reciprocal exchange between the actors. These results suggest that mechanisms to detect unfair reciprocity in third-party social exchanges do not require domain-general higher cognitive ability based on proportionally larger brains, but rather emerge from the cooperative and pro-social tendencies of species, and thereby suggest this ability evolved in multiple primate lineages. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Relationship between cortical state and spiking activity in the lateral geniculate nucleus of marmosets

PubMed Central

Pietersen, Alexander N.J.; Cheong, Soon Keen; Munn, Brandon; Gong, Pulin; Solomon, Samuel G.

2017-01-01

Key points How parallel are the primate visual pathways? In the present study, we demonstrate that parallel visual pathways in the dorsal lateral geniculate nucleus (LGN) show distinct patterns of interaction with rhythmic activity in the primary visual cortex (V1).In the V1 of anaesthetized marmosets, the EEG frequency spectrum undergoes transient changes that are characterized by fluctuations in delta‐band EEG power.We show that, on multisecond timescales, spiking activity in an evolutionary primitive (koniocellular) LGN pathway is specifically linked to these slow EEG spectrum changes. By contrast, on subsecond (delta frequency) timescales, cortical oscillations can entrain spiking activity throughout the entire LGN.Our results are consistent with the hypothesis that, in waking animals, the koniocellular pathway selectively participates in brain circuits controlling vigilance and attention. Abstract The major afferent cortical pathway in the visual system passes through the dorsal lateral geniculate nucleus (LGN), where nerve signals originating in the eye can first interact with brain circuits regulating visual processing, vigilance and attention. In the present study, we investigated how ongoing and visually driven activity in magnocellular (M), parvocellular (P) and koniocellular (K) layers of the LGN are related to cortical state. We recorded extracellular spiking activity in the LGN simultaneously with local field potentials (LFP) in primary visual cortex, in sufentanil‐anaesthetized marmoset monkeys. We found that asynchronous cortical states (marked by low power in delta‐band LFPs) are linked to high spike rates in K cells (but not P cells or M cells), on multisecond timescales. Cortical asynchrony precedes the increases in K cell spike rates by 1–3 s, implying causality. At subsecond timescales, the spiking activity in many cells of all (M, P and K) classes is phase‐locked to delta waves in the cortical LFP, and more cells are phase�

Describing Ovarian Cycles, Pregnancy Characteristics, and the Use of Contraception in Female White-faced Marmosets, Callithrix geoffroyi

PubMed Central

MUSTOE, AARYN C.; JENSEN, HEATHER A.; FRENCH, JEFFREY A.

2012-01-01

Endocrine data and characteristics of nonconceptive ovarian cycling and pregnancy are limited within the genus Callithrix to the common marmoset (C. jacchus) and Wied's black tufted-ear marmoset (C. kuhlii). This paper presents patterns of urinary pregnandiol-3-glucuronide (PdG) excretion, as determined by enzyme immunoassay, throughout the course of ovarian cycling and pregnancy in white-faced marmosets (C. geoffroyi). Furthermore, characteristics of reproductive parameters including litter size, duration of gestation, maternal age, and information about ovarian cycling following administration of contraceptives are also described. A steep increase in PdG, an indication of ovulation, characterizes normative ovarian cycles, with peak-to-peak intervals between cycles being 27.82 ± 1.49 days in length. PdG excretion (μg/mg Cr) across pregnancy peaked during the 1st and 2nd trimesters (1st = 20.71 ± 2.98, 2nd = 21.16 ± 2.60) and declined gradually to near preconception levels over the 3rd trimester until parturition (3rd = 5.74 ± 1.60). Gestation lasted 148.55 ± 1.89 days. Most pregnancies (82.8%) resulted in an immediate postpartum ovulation (PPO) of 17.45 ± 2.22 days with 58.3% of PPOs resulting in conception. No differences in PdG excretion during the 1st trimester between full pregnancies and miscarriages were found, and pregnancy characteristics such as litter size, duration of gestation, and maternal age were not associated with PdG concentrations. Administration of cloprostenol resulted in shorter cycle durations, but ovulation was detectable with similar concentrations of peak PdG to a normal non-conceptive cycle. Conversely, medroxyprogesterone acetate (DMPA) injections resulted in little to no PdG excretion across the ovarian cycle, with both methods of contraception providing effective prevention of conception. Overall, these results show that strong similarities in reproductive parameters persist within the genus Callithrix and to a lesser extent

Retinal Origin of Direction Selectivity in the Superior Colliculus

PubMed Central

Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron; Koren, David; Jin, Yanjiao; Liu, Xiaorong; Wei, Wei; Cang, Jianhua

2017-01-01

Detecting visual features in the environment such as motion direction is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. Here, we optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly-tuned retinal ganglion cells. The direction selective retinal input is linearly amplified by the intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using 2-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC, and reveal a central visual deficit as a consequence of altered feature selectivity in the retina. PMID:28192394

Interlayer neurones in the rat superior colliculus: a tracer study using Dil/Di-ASP.

PubMed

Hilbig, H; Schierwagen, A

1994-01-12

Five different populations of interlayer neurones (ILNs) can be described after DiI/Di-ASP tracing in rat superior colliculus (SC). All of these labelled neurones preferentially lay in the rostro-medial part of the SC. Most of them are located in the stratum opticum and in the stratum griseum superficiale. Our results indicate that ILNs represent a minority of neurones in the superficial layers but may constitute a substantial population of neurones in the stratum opticum connecting the visual and the multimodal collicular layers.

Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues.

PubMed

Carrion, Ricardo; Brasky, Kathleen; Mansfield, Keith; Johnson, Curtis; Gonzales, Monica; Ticer, Anysha; Lukashevich, Igor; Tardif, Suzette; Patterson, Jean

2007-06-01

Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

Use of alternative plant resources by common marmosets (Callithrix jacchus) in the semi-arid caatinga scrub forests of northeastern Brazil.

PubMed

Amora, Tacyana Duarte; Beltrão-Mendes, Raone; Ferrari, Stephen F

2013-04-01

The common marmoset (Callithrix jacchus) is amply distributed in the Brazilian Northeast, but little is known of its ecology in the semi-arid Caatinga scrublands. The present study provides the first detailed data on the composition of the diet of C. jacchus in Caatinga ecosystems, derived from observations at four sites in the state of Sergipe. While exudate sources were gouged at all four sites in a manner typical of the species, fruit was the principal component of the diet at the main study site during most months, and a number of unusual items were eaten, including leaves, and the reproductive parts of cacti and bromeliads. These plants are rarely recorded in marmoset diets, but are common in caatinga habitats. Leaves were ingested during 5 of the 8 months monitored at the main study site, reaching 39.74% of the diet in 1 month, and appeared to be an alternative fallback food to plant exudates during periods when fruit was scarce. Three species of cactus provided both flowers and fruits, while the terrestrial bromeliad, Encholirium spectabile, provided nectar (30.81% of the diet in November). Approximately half of the plant species (and three families) identified in this study had not been recorded previously in the diet of Callithrix. Overall, the data suggest that, while the marmosets exploit the same types of plant foods in the Caatinga, the resource base is quite distinct from that of the Atlantic Forest. Other differences, such as relatively small groups and large home ranges, may contribute to divergent ecological patterns, which require more systematic investigation. Am. J. Primatol. 75:333-341, 2013. © 2012 Wiley Periodicals, Inc. © 2012 Wiley Periodicals, Inc.

Distinct Neural Activities in Premotor Cortex during Natural Vocal Behaviors in a New World Primate, the Common Marmoset (Callithrix jacchus).

PubMed

Roy, Sabyasachi; Zhao, Lingyun; Wang, Xiaoqin

2016-11-30

Although evidence from human studies has long indicated the crucial role of the frontal cortex in speech production, it has remained uncertain whether the frontal cortex in nonhuman primates plays a similar role in vocal communication. Previous studies of prefrontal and premotor cortices of macaque monkeys have found neural signals associated with cue- and reward-conditioned vocal production, but not with self-initiated or spontaneous vocalizations (Coudé et al., 2011; Hage and Nieder, 2013), which casts doubt on the role of the frontal cortex of the Old World monkeys in vocal communication. A recent study of marmoset frontal cortex observed modulated neural activities associated with self-initiated vocal production (Miller et al., 2015), but it did not delineate whether these neural activities were specifically attributed to vocal production or if they may result from other nonvocal motor activity such as orofacial motor movement. In the present study, we attempted to resolve these issues and examined single neuron activities in premotor cortex during natural vocal exchanges in the common marmoset (Callithrix jacchus), a highly vocal New World primate. Neural activation and suppression were observed both before and during self-initiated vocal production. Furthermore, by comparing neural activities between self-initiated vocal production and nonvocal orofacial motor movement, we identified a subpopulation of neurons in marmoset premotor cortex that was activated or suppressed by vocal production, but not by orofacial movement. These findings provide clear evidence of the premotor cortex's involvement in self-initiated vocal production in natural vocal behaviors of a New World primate. Human frontal cortex plays a crucial role in speech production. However, it has remained unclear whether the frontal cortex of nonhuman primates is involved in the production of self-initiated vocalizations during natural vocal communication. Using a wireless multichannel neural

Hierarchical equivalence of somatosensory areas I and II for tactile processing in the cerebral cortex of the marmoset monkey.

PubMed

Zhang, H Q; Zachariah, M K; Coleman, G T; Rowe, M J

2001-05-01

Responsiveness of the first somatosensory area (SI) of the cerebral cortex was investigated in the marmoset monkey (Callithrix jacchus) in association with cooling-induced, reversible inactivation of the second somatosensory area, SII. The aim was to determine whether SI responsiveness to peripheral tactile stimulation depends on SII and therefore whether SI and SII in the marmoset occupy hierarchically equivalent positions in a parallel organizational scheme for thalamocortical tactile processing as appears to be the case in nonprimate mammals. Inactivation of SII was achieved when the temperature over SII was lowered to < or =12 degrees C, as indicated by abolition of the SII-evoked potentials generated by brief tap stimuli to the hand or foot, and by abolition of tactile responses in single SII neurons located at the margin beneath the block. The effect of SII inactivation on SI-evoked potentials was examined in 16 experiments by simultaneous recording of the SI- and SII-evoked potentials. SI-evoked potentials were never abolished and remained unaffected in 11 cases. In three experiments there was a small reduction in amplitude and inconsistent effects in the remaining two. Responsiveness to controlled tactile stimuli was examined quantitatively in 31 individual SI neurons of different functional classes before, during, and after the inactivation of SII. Tactile responsiveness in individual SI neurons was never abolished by SII inactivation, remaining unchanged in 20 neurons (65%) while undergoing some reduction in the remaining 11 SI neurons (35%). This reduction of tactile responsiveness in one-third of SI neurons is most likely attributable to a removal of a facilitatory influence emanating from SII, based on the observation that background activity of the affected neurons was also reduced. Furthermore, phase locking of SI responses to vibrotactile stimulation was unchanged when SII was inactivated. The retention of responsiveness in SI neurons when SII was

Consistent inter-individual differences in common marmosets (Callithrix jacchus) in Boldness-Shyness, Stress-Activity, and Exploration-Avoidance.

PubMed

Šlipogor, Vedrana; Gunhold-de Oliveira, Tina; Tadić, Zoran; Massen, Jorg J M; Bugnyar, Thomas

2016-09-01

The study of animal personality, defined as consistent inter-individual differences in correlated behavioral traits stable throughout time and/or contexts, has recently become one of the fastest growing areas in animal biology, with study species ranging from insects to non-human primates. The latter have, however, only occasionally been tested with standardized experiments. Instead their personality has usually been assessed using questionnaires. Therefore, this study aimed to test 21 common marmosets (Callithrix jacchus) living in three family groups, in five different experiments, and their corresponding controls. We found that behavioral differences between our animals were not only consistent over time, but also across different contexts. Moreover, the consistent behaviors formed a construct of four major non-social personality components: Boldness-Shyness in Foraging, Boldness-Shyness in Predation, Stress-Activity, and Exploration-Avoidance. We found no sex or age differences in these components, but our results did reveal differences in Exploration-Avoidance between the three family groups. As social environment can have a large influence on behavior of individuals, our results may suggest group-level similarity in personality (i.e., "group personality") in common marmosets, a species living in highly cohesive social groups. Am. J. Primatol. 78:961-973, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Digital cranial endocast of Hyopsodus (Mammalia, "Condylarthra"): a case of paleogene terrestrial echolocation?

PubMed

Orliac, Maeva J; Argot, Christine; Gilissen, Emmanuel

2012-01-01

We here describe the endocranial cast of the Eocene archaic ungulate Hyopsodus lepidus AMNH 143783 (Bridgerian, North America) reconstructed from X-ray computed microtomography data. This represents the first complete cranial endocast known for Hyopsodontinae. The Hyopsodus endocast is compared to other known "condylarthran" endocasts, i. e. those of Pleuraspidotherium (Pleuraspidotheriidae), Arctocyon (Arctocyonidae), Meniscotherium (Meniscotheriidae), Phenacodus (Phenacodontidae), as well as to basal perissodactyls (Hyracotherium) and artiodactyls (Cebochoerus, Homacodon). Hyopsodus presents one of the highest encephalization quotients of archaic ungulates and shows an "advanced version" of the basal ungulate brain pattern, with a mosaic of archaic characters such as large olfactory bulbs, weak ventral expansion of the neopallium, and absence of neopallium fissuration, as well as more specialized ones such as the relative reduction of the cerebellum compared to cerebrum or the enlargement of the inferior colliculus. As in other archaic ungulates, Hyopsodus midbrain exposure is important, but it exhibits a dorsally protruding largely developed inferior colliculus, a feature unique among "Condylarthra". A potential correlation between the development of the inferior colliculus in Hyopsodus and the use of terrestrial echolocation as observed in extant tenrecs and shrews is discussed. The detailed analysis of the overall morphology of the postcranial skeleton of Hyopsodus indicates a nimble, fast moving animal that likely lived in burrows. This would be compatible with terrestrial echolocation used by the animal to investigate subterranean habitat and/or to minimize predation during nocturnal exploration of the environment.

Digital Cranial Endocast of Hyopsodus (Mammalia, “Condylarthra”): A Case of Paleogene Terrestrial Echolocation?

PubMed Central

Orliac, Maeva J.; Argot, Christine; Gilissen, Emmanuel

2012-01-01

We here describe the endocranial cast of the Eocene archaic ungulate Hyopsodus lepidus AMNH 143783 (Bridgerian, North America) reconstructed from X-ray computed microtomography data. This represents the first complete cranial endocast known for Hyopsodontinae. The Hyopsodus endocast is compared to other known “condylarthran” endocasts, i. e. those of Pleuraspidotherium (Pleuraspidotheriidae), Arctocyon (Arctocyonidae), Meniscotherium (Meniscotheriidae), Phenacodus (Phenacodontidae), as well as to basal perissodactyls (Hyracotherium) and artiodactyls (Cebochoerus, Homacodon). Hyopsodus presents one of the highest encephalization quotients of archaic ungulates and shows an “advanced version” of the basal ungulate brain pattern, with a mosaic of archaic characters such as large olfactory bulbs, weak ventral expansion of the neopallium, and absence of neopallium fissuration, as well as more specialized ones such as the relative reduction of the cerebellum compared to cerebrum or the enlargement of the inferior colliculus. As in other archaic ungulates, Hyopsodus midbrain exposure is important, but it exhibits a dorsally protruding largely developed inferior colliculus, a feature unique among “Condylarthra”. A potential correlation between the development of the inferior colliculus in Hyopsodus and the use of terrestrial echolocation as observed in extant tenrecs and shrews is discussed. The detailed analysis of the overall morphology of the postcranial skeleton of Hyopsodus indicates a nimble, fast moving animal that likely lived in burrows. This would be compatible with terrestrial echolocation used by the animal to investigate subterranean habitat and/or to minimize predation during nocturnal exploration of the environment. PMID:22347998

A dimensional approach to modeling symptoms of neuropsychiatric disorders in the marmoset monkey

PubMed Central

Oikonomidis, Lydia; Santangelo, Andrea M.; Shiba, Yoshiro; Clarke, F. Hannah; Robbins, Trevor W.

2017-01-01

ABSTRACT Some patients suffering from the same neuropsychiatric disorder may have no overlapping symptoms whilst others may share symptoms common to other distinct disorders. Therefore, the Research Domain Criteria initiative recognises the need for better characterisation of the individual symptoms on which to focus symptom‐based treatment strategies. Many of the disorders involve dysfunction within the prefrontal cortex (PFC) and so the marmoset, due to their highly developed PFC and small size, is an ideal species for studying the neurobiological basis of the behavioural dimensions that underlie these symptoms.Here we focus on a battery of tests that address dysfunction spanning the cognitive (cognitive inflexibility and working memory), negative valence (fear generalisation and negative bias) and positive valence (anhedonia) systems pertinent for understanding disorders such as ADHD, Schizophrenia, Anxiety, Depression and OCD. Parsing the separable prefrontal and striatal circuits and identifying the selective neurochemical modulation (serotonin vs dopamine) that underlie cognitive dysfunction have revealed counterparts in the clinical domain. Aspects of the negative valence system have been explored both at individual‐ (trait anxiety and genetic variation in serotonin transporter) and circuit‐based levels enabling the understanding of generalisation processes, negative biases and differential responsiveness to SSRIs. Within the positive valence system, the combination of cardiovascular and behavioural measures provides a framework for understanding motivational, anticipatory and consummatory aspects of anhedonia and their neurobiological mechanisms. Together, the direct comparison of experimental findings in marmosets with clinical studies is proving an excellent translational model to address the behavioural dimensions and neurobiology of neuropsychiatric symptoms. © 2016 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc

Developmental origins of pregnancy loss in the adult female common marmoset monkey (Callithrix jacchus).

PubMed

Rutherford, Julienne N; deMartelly, Victoria A; Layne Colon, Donna G; Ross, Corinna N; Tardif, Suzette D

2014-01-01

The impact of the intrauterine environment on the developmental programming of adult female reproductive success is still poorly understood and potentially underestimated. Litter size variation in a nonhuman primate, the common marmoset monkey (Callithrix jacchus), allows us to model the effects of varying intrauterine environments (e.g. nutrient restriction, exposure to male womb-mates) on the risk of losing fetuses in adulthood. Our previous work has characterized the fetuses of triplet pregnancies as experiencing intrauterine nutritional restriction. We used over a decade of demographic data from the Southwest National Primate Research Center common marmoset colony. We evaluated differences between twin and triplet females in the number of pregnancies they produce and the proportion of those pregnancies that ended in fetal loss. We found that triplet females produced the same number of total offspring as twin females, but lost offspring during pregnancy at a significantly higher rate than did twins (38% vs. 13%, p = 0.02). Regardless of their own birth weight or the sex ratio of the litter the experienced as fetuses, triplet females lost more fetuses than did twins. Females with a male littermate experienced a significant increase in the proportion of stillbirths. These striking findings anchor pregnancy loss in the mother's own fetal environment and development, underscoring a "Womb to Womb" view of the lifecourse and the intergenerational consequences of development. This has important translational implications for understanding the large proportion of human stillbirths that are unexplained. Our findings provide strong evidence that a full understanding of mammalian life history and reproductive biology requires a developmental foundation.

Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets.

PubMed

Guy, Joseph R; Sati, Pascal; Leibovitch, Emily; Jacobson, Steven; Silva, Afonso C; Reich, Daniel S

2016-01-15

MRI has the advantage of sampling large areas of tissue and locating areas of interest in 3D space in both living and ex vivo systems, whereas histology has the ability to examine thin slices of ex vivo tissue with high detail and specificity. Although both are valuable tools, it is currently difficult to make high-precision comparisons between MRI and histology due to large differences inherent to the techniques. A method combining the advantages would be an asset to understanding the pathological correlates of MRI. 3D-printed brain holders were used to maintain marmoset brains in the same orientation during acquisition of ex vivo MRI and pathologic cutting of the tissue. The results of maintaining this same orientation show that sub-millimeter, discrete neuropathological features in marmoset brain consistently share size, shape, and location between histology and ex vivo MRI, which facilitates comparison with serial imaging acquired in vivo. Existing methods use computational approaches sensitive to data input in order to warp histologic images to match large-scale features on MRI, but the new method requires no warping of images, due to a preregistration accomplished in the technique, and is insensitive to data formatting and artifacts in both MRI and histology. The simple method of using 3D-printed brain holders to match brain orientation during pathologic sectioning and MRI acquisition enables rapid and precise comparison of small features seen on MRI to their underlying histology. Published by Elsevier B.V.

Effects of beta-blockers and nicardipine on oxotremorine-induced tremor in common marmosets.

PubMed

Mitsuda, M; Nomoto, M; Iwata, S

1999-10-01

Effects of beta-blockers (propranolol, arotinolol and nipradilol) and a Ca2+ channel blocker (nicardipine) on oxotremorine-induced tremor were studied in common marmosets. Generalized tremor was elicited by an intraperitoneal administration of 0.25 mg/kg oxotremorine. Intensity of the tremor was classified into 7 degrees, and it was evaluated every 10 min. The total intensity of oxotremorine-induced tremor for each drug was expressed as "points", which were the sum of tremor intensity scores evaluated every 10 min up to 190 min following the administration of oxotremorine. Beta-blockers significantly suppressed the tremor. On the other hand, the Ca2+ channel blocker exacerbated the tremor.

Inhalation and Percutaneous Toxicokinetics of Sulfur Mustard and Its adducts in Hairless Guinea Pigs and Marmosets. Efficacy of Nasal Scavengers

DTIC Science & Technology

2004-08-01

As a follow-up to DAMDl7-94-V-4OO9, the inhalation toxicokinetics of sulfur mustard are studied in more detail in the hairless guinea pig as well as...in a species more relevant for man, i.e., the marmoset. Furthermore, its percutaneous toxicokinetics are studied in the hairless guinea pig at a lower

Sleep and Alertness Management III: Effects of a Nap and Hypnotics on Performance During the Late Evening, Night and Early Morning in Marmosets

DTIC Science & Technology

2006-11-01

positive reinforcement as a motivating stimulus (small pieces of marshmallow ) has been used to asses the HEC [Philippens et al. 2000]. The marmoset...apparatus using positive reinforcement as a motivating stimulus for the animals (small pieces of marshmallow ) has been used to asses the Hand-eye

Molecular and neurochemical substrates of the audiogenic seizure strains: The GASH:Sal model.

PubMed

Prieto-Martín, Ana I; Aroca-Aguilar, J Daniel; Sánchez-Sánchez, Francisco; Muñoz, Luis J; López, Dolores E; Escribano, Julio; de Cabo, Carlos

2017-06-01

Animal models of audiogenic epilepsy are useful tools to understand the mechanisms underlying human reflex epilepsies. There is accumulating evidence regarding behavioral, anatomical, electrophysiological, and genetic substrates of audiogenic seizure strains, but there are still aspects concerning their neurochemical basis that remain to be elucidated. Previous studies have shown the involved of γ-amino butyric acid (GABA) in audiogenic seizures. The aim of our research was to clarify the role of the GABAergic system in the generation of epileptic seizures in the genetic audiogenic seizure-prone hamster (GASH:Sal) strain. We studied the K + /Cl - cotransporter KCC2 and β2-GABAA-type receptor (GABAAR) and β3-GABAAR subunit expressions in the GASH:Sal both at rest and after repeated sound-induced seizures in different brain regions using the Western blot technique. We also sequenced the coding region for the KCC2 gene both in wild- type and GASH:Sal hamsters. Lower expression of KCC2 protein was found in GASH:Sal when compared with controls at rest in several brain areas: hippocampus, cortex, cerebellum, hypothalamus, pons-medulla, and mesencephalon. Repeated induction of seizures caused a decrease in KCC2 protein content in the inferior colliculus and hippocampus and an increase in the pons-medulla. When compared to controls, the basal β 2 -GABA A R subunit in the GASH:Sal was overexpressed in the inferior colliculus, rest of the mesencephalon, and cerebellum, whereas basal β 3 subunit levels were lower in the inferior colliculus and rest of the mesencephalon. Repeated seizures increased β2 both in the inferior colliculus and in the hypothalamus and β 3 in the hypothalamus. No differences in the KCC2 gene-coding region were found between GASH:Sal and wild-type hamsters. These data indicate that GABAergic system functioning is impaired in the GASH:Sal strain, and repeated seizures seem to aggravate this dysfunction. These results have potential clinical

Inhibition of allergic encephalomyelitis in marmosets by vaccination with recombinant vaccinia virus encoding for myelin basic protein.

PubMed

Genain, C P; Gritz, L; Joshi, N; Panicali, D; Davis, R L; Whitaker, J N; Letvin, N L; Hauser, S L

1997-11-01

A primary demyelinating form of experimental allergic encephalomyelitis (EAE) resembling human multiple sclerosis (MS) occurs in Callithrix jacchus marmosets following immunization with human white matter. Participation of a T-cell immune response against myelin basic protein (MBP) in this disease model is supported by observations of increased reactivity against MBP in PBMC and of adoptive transfer of an inflammatory form of EAE by MBP-reactive T-cells. To evaluate the effects of ectopic presentation of MBP on marmoset EAE, animals were vaccinated prior to induction of EAE by subcutaneous injection of attenuated strains of vaccinia virus genetically engineered to contain either the entire coding sequence for human MBP (vT15) or the equine herpes virus glycoprotein gH gene (vAbT249). Vaccination with vT15 was followed by transient cytoplasmic and surface membrane expression of MBP in circulating PBMC (15-45 days). The onset of clinical EAE after immunization (pi) was markedly delayed in vT15-vaccinated animals (37-97 days pi, n = 4) compared to vAbT249-vaccinated controls (14-18 days pi, n = 3). Proliferative responses against MBP but not against vaccinia antigens or phytohemagglutinin were suppressed in protected animals. Thus, development of attenuated live viruses carrying genes for myelin antigens could be useful for induction of immunologic tolerance and for modulation of autoimmune demyelination.

The influence of vibrissal somatosensory processing in rat superior colliculus on prey capture.

PubMed

Favaro, P D N; Gouvêa, T S; de Oliveira, S R; Vautrelle, N; Redgrave, P; Comoli, E

2011-03-10

The lateral part of intermediate layer of superior colliculus (SCl) is a critical substrate for successful predation by rats. Hunting-evoked expression of the activity marker Fos is concentrated in SCl while prey capture in rats with NMDA lesions in SCl is impaired. Particularly affected are rapid orienting and stereotyped sequences of actions associated with predation of fast moving prey. Such deficits are consistent with the view that the deep layers of SC are important for sensory guidance of movement. Although much of the relevant evidence involves visual control of movement, less is known about movement guidance by somatosensory input from vibrissae. Indeed, our impression is that prey contact with whiskers is a likely stimulus to trigger predation. Moreover, SCl receives whisker and orofacial somatosensory information directly from trigeminal complex, and indirectly from zona incerta, parvicelular reticular formation and somatosensory barrel cortex. To better understand sensory guidance of predation by vibrissal information we investigated prey capture by rats after whisker removal and the role of superior colliculus (SC) by comparing Fos expression after hunting with and without whiskers. Rats were allowed to hunt cockroaches, after which their whiskers were removed. Two days later they were allowed to hunt cockroaches again. Without whiskers the rats were less able to retain the cockroaches after capture and less able to pursue them in the event of the cockroach escaping. The predatory behaviour of rats with re-grown whiskers returned to normal. In parallel, Fos expression in SCl induced by predation was significantly reduced in whiskerless animals. We conclude that whiskers contribute to the efficiency of rat prey capture and that the loss of vibrissal input to SCl, as reflected by reduced Fos expression, could play a critical role in predatory deficits of whiskerless rats. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Development of methods to measure humoral immune responses against selected antigens in the common marmoset (Callithrix jacchus) and the effect of pyridostigmine bromide administration.

PubMed

Griffiths, Gareth D; Hornby, Rebecca J; Jagger, Christopher P; Brown, Alan P; Stoten, Adam; Pearce, Peter C; Scott, Leah; Pritchard, David I

2006-12-05

This methodological study was carried out in preparation for a major long term study, also reported in this volume, which was designed to investigate whether the combination of vaccines and pyridostigmine bromide (PB) could have been responsible for adverse signs and symptoms reported by a number of veterans of the 1990/1991 Gulf conflict. In this context, the marmoset has been used to model aspects of the human immune system. The purposes of this methodological study were to select appropriate immunochemical reagents to measure humoral responses induced in marmosets in response to selected health and hygiene and biological warfare vaccines and to initially assess the effects of PB on the responses recorded. Vaccines were administered at 1/5th of a human dose, and also investigated in combination with the nerve agent pretreatment compound PB. PB dosing was selected to induce an inhibition of erythrocyte acetylcholinesterase by 30%. In order to assess the functionality of the immune system, antibody responses to a neo-antigen (keyhole limpet haemocyanin--KLH), administered some 2 months following the completion of the vaccination schedule, were measured. The present study identified appropriate isotyping reporter reagents which cross-reacted with equivalent marmoset immunoglobulins. Robust antibody responses were identified against anthrax protective antigen (PA), whole cell pertussis vaccine and KLH, while weaker responses were measured against cholera and typhoid vaccines. The killed whole cell plague vaccine induced a response which was at the limit of detection of the assay. Coadministered PB had no discernable effect on immunological responses in this study.

Developmental Origins of Pregnancy Loss in the Adult Female Common Marmoset Monkey (Callithrix jacchus)

PubMed Central

Rutherford, Julienne N.; deMartelly, Victoria A.; Layne Colon, Donna G.; Ross, Corinna N.; Tardif, Suzette D.

2014-01-01

Background The impact of the intrauterine environment on the developmental programming of adult female reproductive success is still poorly understood and potentially underestimated. Litter size variation in a nonhuman primate, the common marmoset monkey (Callithrix jacchus), allows us to model the effects of varying intrauterine environments (e.g. nutrient restriction, exposure to male womb-mates) on the risk of losing fetuses in adulthood. Our previous work has characterized the fetuses of triplet pregnancies as experiencing intrauterine nutritional restriction. Methodology/Principal Findings We used over a decade of demographic data from the Southwest National Primate Research Center common marmoset colony. We evaluated differences between twin and triplet females in the number of pregnancies they produce and the proportion of those pregnancies that ended in fetal loss. We found that triplet females produced the same number of total offspring as twin females, but lost offspring during pregnancy at a significantly higher rate than did twins (38% vs. 13%, p = 0.02). Regardless of their own birth weight or the sex ratio of the litter the experienced as fetuses, triplet females lost more fetuses than did twins. Females with a male littermate experienced a significant increase in the proportion of stillbirths. Conclusions/Significance These striking findings anchor pregnancy loss in the mother’s own fetal environment and development, underscoring a "Womb to Womb" view of the lifecourse and the intergenerational consequences of development. This has important translational implications for understanding the large proportion of human stillbirths that are unexplained. Our findings provide strong evidence that a full understanding of mammalian life history and reproductive biology requires a developmental foundation. PMID:24871614

Neural Prediction of Multidimensional Decisions in Monkey Superior Colliculus

NASA Astrophysics Data System (ADS)

Hasegawa, Ryohei P.; Hasegawa, Yukako T.; Segraves, Mark A.

To examine the function of the superior colliculus (SC) in decision-making processes and the application of its single trial activity for “neural mind reading,” we recorded from SC deep layers while two monkeys performed oculomotor go/no-go tasks. We have recently focused on monitoring single trial activities in single SC neurons, and designed a virtual decision function (VDF) to provide a good estimation of single-dimensional decisions (go/no-go decisions for a cue presented at a specific visual field, a response field of each neuron). In this study, we used two VDFs for multidimensional decisions (go/no-go decisions at two cue locations) with the ensemble activity which was simultaneously recorded from a small group (4 to 6) of neurons at both sides of the SC. VDFs predicted cue locations as well as go/no-go decisions. These results suggest that monitoring of ensemble SC activity had sufficient capacity to predict multidimensional decisions on a trial-by-trial basis, which is an ideal candidate to serve for cognitive brain-machine interfaces (BMI) such as two-dimensional word spellers.

Role of the superior colliculus in choosing mixed-strategy saccades.

PubMed

Thevarajah, Dhushan; Mikulić, Areh; Dorris, Michael C

2009-02-18

Game theory outlines optimal response strategies during mixed-strategy competitions. The neural processes involved in choosing individual strategic actions, however, remain poorly understood. Here, we tested whether the superior colliculus (SC), a brain region critical for generating sensory-guided saccades, is also involved in choosing saccades under strategic conditions. Monkeys were free to choose either of two saccade targets as they competed against a computer opponent during the mixed-strategy game "matching pennies." The accuracy with which presaccadic SC activity predicted upcoming choice gradually increased in the time leading up to the saccade. Probing the SC with suprathreshold stimulation demonstrated that these evolving signals were functionally involved in preparing strategic saccades. Finally, subthreshold stimulation of the SC increased the likelihood that contralateral saccades were selected. Together, our results suggest that motor regions of the brain play an active role in choosing strategic actions rather than passively executing those prespecified by upstream executive regions.

The effects of lesions of the superior colliculus on locomotor orientation and the orienting reflex in the rat.

PubMed

Goodale, M A; Murison, R C

1975-05-02

The effects of bilateral removal of the superior colliculus or visual cortex on visually guided locomotor movements in rats performing a brightness discrimination task were investigated directly with the use of cine film. Rats with collicular lesions showed patterns of locomotion comparable to or more efficient than those of normal animals when approaching one of 5 small doors located at one end of a large open area. In contrast, animals with large but incomplete lesions of visual cortex were distinctly impaired in their visual control of approach responses to the same stimuli. On the other hand, rats with collicular damage showed no orienting reflex or evidence of distraction in the same task when novel visual or auditory stimuli were presented. However, both normal and visual-decorticate rats showed various components of the orienting reflex and disturbance in task performance when the same novel stimuli were presented. These results suggest that although the superior colliculus does not appear to be essential to the visual control of locomotor orientation, this midbrain structure might participate in the mediation of shifts in visual fixation and attention. Visual cortex, while contributing to visuospatial guidance of locomotor movements, might not play a significant role in the control and integration of the orienting reflex.

Edaravone is a free radical scavenger that protects against laser-induced choroidal neovascularization in mice and common marmosets.

PubMed

Masuda, Tomomi; Shimazawa, Masamitsu; Takata, Shinsuke; Nakamura, Shinsuke; Tsuruma, Kazuhiro; Hara, Hideaki

2016-05-01

Choroidal neovascularization (CNV) is a main characteristic in exudative type of age-related macular degeneration (AMD). Our study aimed to evaluate the effects of edaravone, a free radical scavenger on laser-induced CNV. CNV was induced by laser photocoagulation to the subretinal choroidal area of mice and common marmosets. Edaravone was administered either intraperitoneally twice a day for 2 weeks or intravenously just once after laser photocoagulation. The effects of edaravone on laser-induced CNV were evaluated by fundus fluorescein angiography, CNV area measurements, and the expression of 4-hydroxy-2-nonenal (4-HNE) modified proteins, a marker of oxidative stress. Furthermore, the effects of edaravone on the production of H2O2-induced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF)-induced cell proliferation were evaluated using human retinal pigment epithelium cells (ARPE-19) and human retinal microvascular endothelial cells, respectively. CNV areas in the edaravone-treated group were significantly smaller in mice and common marmosets. The expression of 4-HNE modified proteins was upregulated 3 h after laser photocoagulation, and intravenously administered edaravone decreased it. In in vitro studies, edaravone inhibited H2O2-induced ROS production and VEGF-induced cell proliferation. These findings suggest that edaravone may protect against laser-induced CNV by inhibiting oxidative stress and endothelial cell proliferation. Copyright © 2016 Elsevier Ltd. All rights reserved.

The serotonin 5-HT₁A receptor agonist tandospirone improves executive function in common marmosets.

PubMed

Baba, Satoko; Murai, Takeshi; Nakako, Tomokazu; Enomoto, Takeshi; Ono, Michiko; Shimizu, Isao; Ikeda, Kazuhito

2015-01-01

Previous pilot clinical studies have shown that the serotonin 5-HT1A receptor agonist tandospirone has beneficial effect on cognitive deficits associated with schizophrenia. In the present study, we evaluated the cognitive efficacy of tandospirone, given alone or in combination with the antipsychotic blonanserin, risperidone or haloperidol, on executive function in marmosets using the object retrieval with detour (ORD) task. Treatment with tandospirone alone at 20 and 40 mg/kg increased the number of correct responses in the difficult trial, while risperidone (0.3mg/kg) and haloperidol (0.3mg/kg) decreased the number of correct responses in this trial. On the other hand, blonanserin (0.1-0.3mg/kg), an atypical antipsychotic highly selective for dopamine D2/D3 and serotonin 5-HT2A receptors, did not affect the number of correct responses in both the easy and difficult trials. Co-treatment with tandospirone (20mg/kg) and risperidone (0.1-0.3mg/kg) or haloperidol (0.1-0.3mg/kg) did not improve animals' performance in the difficult trial. However, co-treatment with tandospirone and blonanserin (0.1-0.3mg/kg) increased the number of correct responses in the difficult trial. In addition, treatment with the dopamine D1 receptor agonist SKF-81297 at 1mg/kg increased marmosets correct responses in the difficult trial. These results suggest that tandospirone is a promising candidate for the treatment of cognitive deficits associated with schizophrenia and that adjunctive treatment with tandospirone and blonanserin is more appropriate for cognitive deficits than combination therapy with tandospirone and risperidone or haloperidol. The results of this study also indicate that the putative mechanism of action of tandospirone might be related to enhancement of dopamine neurotransmission via activation of the 5-HT1A receptor. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)

PubMed Central

Via, Laura E.; Weiner, Danielle M.; Schimel, Daniel; Lin, Philana Ling; Dayao, Emmanuel; Tankersley, Sarah L.; Cai, Ying; Coleman, M. Teresa; Tomko, Jaime; Paripati, Praveen; Orandle, Marlene; Kastenmayer, Robin J.; Tartakovsky, Michael; Rosenthal, Alexander; Portevin, Damien; Eum, Seok Yong; Lahouar, Saher; Gagneux, Sebastien; Young, Douglas B.; Flynn, JoAnne L.

2013-01-01

Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades. PMID:23716617

Natural and Anthropogenic Hybridization in Two Species of Eastern Brazilian Marmosets (Callithrix jacchus and C. penicillata)

PubMed Central

Malukiewicz, Joanna; Boere, Vanner; Fuzessy, Lisieux F.; Grativol, Adriana D.; de Oliveira e Silva, Ita; Pereira, Luiz C. M.; Ruiz-Miranda, Carlos R.; Valença, Yuri M.; Stone, Anne C.

2015-01-01

Animal hybridization is well documented, but evolutionary outcomes and conservation priorities often differ for natural and anthropogenic hybrids. Among primates, an order with many endangered species, the two contexts can be hard to disentangle from one another, which carries important conservation implications. Callithrix marmosets give us a unique glimpse of genetic hybridization effects under distinct natural and human-induced contexts. Here, we use a 44 autosomal microsatellite marker panel to examine genome-wide admixture levels and introgression at a natural C. jacchus and C. penicillata species border along the São Francisco River in NE Brazil and in an area of Rio de Janeiro state where humans introduced these species exotically. Additionally, we describe for the first time autosomal genetic diversity in wild C. penicillata and expand previous C. jacchus genetic data. We characterize admixture within the natural zone as bimodal where hybrid ancestry is biased toward one parental species or the other. We also show evidence that São Francisco River islands are gateways for bidirectional gene flow across the species border. In the anthropogenic zone, marmosets essentially form a hybrid swarm with intermediate levels of admixture, likely from the absence of strong physical barriers to interspecific breeding. Our data show that while hybridization can occur naturally, the presence of physical, even if leaky, barriers to hybridization is important for maintaining species genetic integrity. Thus, we suggest further study of hybridization under different contexts to set well informed conservation guidelines for hybrid populations that often fit somewhere between “natural” and “man-made.” PMID:26061111

Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets.

PubMed

Koshiba, Mamiko; Karino, Genta; Mimura, Koki; Nakamura, Shun; Yui, Kunio; Kunikata, Tetsuya; Yamanouchi, Hideo

2016-01-01

Educational treatment to support social development of children with autism spectrum disorder (ASD) is an important topic in developmental psychiatry. However, it remains difficult to objectively quantify the socio-emotional development of ASD children. To address this problem, we developed a novel analytical method that assesses subjects' complex behaviors using multivariate analysis, 'Behavior Output analysis for Quantitative Emotional State Translation' (BOUQUET). Here, we examine the potential for psycho-cognitive ASD therapy based on comparative evaluations of clinical (human) and experimental (animal) models. Our observations of ASD children (vs. their normally developing siblings) and the domestic chick in socio-sensory deprivation models show the importance of unimodal sensory stimulation, particularly important for tactile- and auditory-biased socialization. Identifying psycho-cognitive elements in early neural development, human newborn infants in neonatal intensive care unit as well as a New World monkey, the common marmoset, also prompted us to focus on the development of voluntary movement against gravity. In summary, striking behavioral similarities between children with ASD and domestic chicks' socio-sensory deprivation models support the role of multimodal sensory-motor integration as a prerequisite step for normal development of socio-emotional and psycho-cognitive functions. Data obtained in the common marmoset model also suggest that switching from primitive anti-gravity reflexes to complex voluntary movement may be a critical milestone for psycho-cognitive development. Combining clinical findings with these animal models, and using multivariate integrative analyses may facilitate the development of effective interventions to improve social functions in infants and in children with neurodevelopmental disorders.

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

Inferior Vena Cava Filter Placement and Removal

MedlinePlus

... Professions Site Index A-Z Inferior Vena Cava Filter Placement and Removal During Inferior Vena Cava (IVC) ... benefits vs. risks? What is Inferior Vena Cava Filter Placement and Removal? In an inferior vena cava ...

Design of Phase II Non-inferiority Trials.

PubMed

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

The binaural masking level difference: cortical correlates persist despite severe brain stem atrophy in progressive supranuclear palsy

PubMed Central

Rowe, James B.; Ghosh, Boyd C. P.; Carlyon, Robert P.; Plack, Christopher J.; Gockel, Hedwig E.

2014-01-01

Under binaural listening conditions, the detection of target signals within background masking noise is substantially improved when the interaural phase of the target differs from that of the masker. Neural correlates of this binaural masking level difference (BMLD) have been observed in the inferior colliculus and temporal cortex, but it is not known whether degeneration of the inferior colliculus would result in a reduction of the BMLD in humans. We used magnetoencephalography to examine the BMLD in 13 healthy adults and 13 patients with progressive supranuclear palsy (PSP). PSP is associated with severe atrophy of the upper brain stem, including the inferior colliculus, confirmed by voxel-based morphometry of structural MRI. Stimuli comprised in-phase sinusoidal tones presented to both ears at three levels (high, medium, and low) masked by in-phase noise, which rendered the low-level tone inaudible. Critically, the BMLD was measured using a low-level tone presented in opposite phase across ears, making it audible against the noise. The cortical waveforms from bilateral auditory sources revealed significantly larger N1m peaks for the out-of-phase low-level tone compared with the in-phase low-level tone, for both groups, indicating preservation of early cortical correlates of the BMLD in PSP. In PSP a significant delay was observed in the onset of the N1m deflection and the amplitude of the P2m was reduced, but these differences were not restricted to the BMLD condition. The results demonstrate that although PSP causes subtle auditory deficits, binaural processing can survive the presence of significant damage to the upper brain stem. PMID:25231610

The binaural masking level difference: cortical correlates persist despite severe brain stem atrophy in progressive supranuclear palsy.

PubMed

Hughes, Laura E; Rowe, James B; Ghosh, Boyd C P; Carlyon, Robert P; Plack, Christopher J; Gockel, Hedwig E

2014-12-15

Under binaural listening conditions, the detection of target signals within background masking noise is substantially improved when the interaural phase of the target differs from that of the masker. Neural correlates of this binaural masking level difference (BMLD) have been observed in the inferior colliculus and temporal cortex, but it is not known whether degeneration of the inferior colliculus would result in a reduction of the BMLD in humans. We used magnetoencephalography to examine the BMLD in 13 healthy adults and 13 patients with progressive supranuclear palsy (PSP). PSP is associated with severe atrophy of the upper brain stem, including the inferior colliculus, confirmed by voxel-based morphometry of structural MRI. Stimuli comprised in-phase sinusoidal tones presented to both ears at three levels (high, medium, and low) masked by in-phase noise, which rendered the low-level tone inaudible. Critically, the BMLD was measured using a low-level tone presented in opposite phase across ears, making it audible against the noise. The cortical waveforms from bilateral auditory sources revealed significantly larger N1m peaks for the out-of-phase low-level tone compared with the in-phase low-level tone, for both groups, indicating preservation of early cortical correlates of the BMLD in PSP. In PSP a significant delay was observed in the onset of the N1m deflection and the amplitude of the P2m was reduced, but these differences were not restricted to the BMLD condition. The results demonstrate that although PSP causes subtle auditory deficits, binaural processing can survive the presence of significant damage to the upper brain stem. Copyright © 2014 the American Physiological Society.

Towards a comprehensive atlas of cortical connections in a primate brain: Mapping tracer injection studies of the common marmoset into a reference digital template.

PubMed

Majka, Piotr; Chaplin, Tristan A; Yu, Hsin-Hao; Tolpygo, Alexander; Mitra, Partha P; Wójcik, Daniel K; Rosa, Marcello G P

2016-08-01

The marmoset is an emerging animal model for large-scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for coregistration of retrograde tracing data on connections of cortical areas into a 3D marmoset brain template, generated from Nissl-stained sections. The procedure results in a series of spatial transformations that are applied to the coordinates of labeled neurons in the different cases, bringing them into common stereotaxic space. We applied this procedure to 17 injections, placed in the frontal lobe of nine marmosets as part of earlier studies. Visualizations of cortical patterns of connections revealed by these injections are supplied as Supplementary Materials. Comparison between the results of the automated and human-based processing of these cases reveals that the centers of injection sites can be reconstructed, on average, to within 0.6 mm of coordinates estimated by an experienced neuroanatomist. Moreover, cell counts obtained in different areas by the automated approach are highly correlated (r = 0.83) with those obtained by an expert, who examined in detail histological sections for each individual. The present procedure enables comparison and visualization of large datasets, which in turn opens the way for integration and analysis of results from many animals. Its versatility, including applicability to archival materials, may reduce the number of additional experiments required to produce the first detailed cortical connectome of a primate brain. J. Comp. Neurol. 524:2161-2181, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Gender and Gonadal Status Differences in Zona Reticularis Expression in Marmoset Monkey Adrenals: Cytochrome b5 Localization With Respect To Cytochrome P450 17,20-Lyase Activity.

PubMed Central

Pattison, J Christina; Saltzman, Wendy; Abbott, David H; Hogan, Brynn K; Nguyen, Ann D; Husen, Bettina; Einspanier, Almuth; Conley, Alan J; Bird., Ian M

2007-01-01

Neonatal marmosets express an adrenal fetal zone comparable to humans. While adult males fail to express a functional ZR, with barely detectable blood DHEA levels, females produce higher levels of DHEA than males in adulthood. We investigated the presence of a putative functional ZR in adult female marmosets. In contrast to males, immunohistochemical analysis showed the ZR marker cytochrome b5 was elevated in the innermost zone in cycling females (compared to testis-intact males), further elevated in the adrenals from anovulatory females, and substantially elevated and continuous in ovariectomized females. As a functional test in vivo, following overnight dexamethasone treatment, cycling and anovulatory females showed higher levels of DHEA relative to males, but DHEA failed to increase in response to ACTH. In direct contrast, while ovariectomized females exhibited lower initial DHEA levels, clear increases were detectable after ACTH administration (p<0.05), suggesting an adrenal origin. The apparent differences in cytochrome b5 expression between groups were also further verified by western blotting of adrenal microsomes, and compared to 17,20-lyase activity; the two parameters were positively correlated (p<0.01) across multiple treatment groups. We conclude that the cycling female marmoset expresses a rudimentary ZR with at least a capacity for DHEA production that becomes significantly ACTH-responsive after anovulation. Expression of cytochrome b5 in this region may be directly or indirectly controlled by gonadal function, and is, at least in part, a critical determinant in the development of an adrenal ZR that is more defined and significantly ACTH-responsive. PMID:17222503

Progression and recovery of Parkinsonism in a chronic progressive MPTP-induction model in the marmoset without persistent molecular and cellular damage.

PubMed

Franke, S K; van Kesteren, R E; Wubben, J A M; Hofman, S; Paliukhovich, I; van der Schors, R C; van Nierop, P; Smit, A B; Philippens, I H C H M

2016-01-15

Chronic exposure to low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in marmoset monkeys was used to model the prodromal stage of Parkinson's disease (PD), and to investigate mechanisms underlying disease progression and recovery. Marmosets were subcutaneously injected with MPTP for a period of 12weeks, 0.5mg/kg once per week, and clinical signs of Parkinsonism, motor- and non-motor behaviors were recorded before, during and after exposure. In addition, postmortem immunohistochemistry and proteomics analysis were performed. MPTP-induced parkinsonian clinical symptoms increased in severity during exposure, and recovered after MPTP administration was ended. Postmortem analyses, after the recovery period, revealed no alteration of the number and sizes of tyrosine hydroxylase (TH)-positive dopamine (DA) neurons in the substantia nigra. Also levels of TH in putamen and caudate nucleus were unaltered, no differences were observed in DA, serotonin or nor-adrenalin levels in the caudate nucleus, and proteomics analysis revealed no global changes in protein expression in these brain areas between treatment groups. Our findings indicate that parkinsonian symptoms can occur without detectable damage at the cellular or molecular level. Moreover, we show that parkinsonian symptoms may be reversible when diagnosed and treated early. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Enhanced visual responses in the superior colliculus in an animal model of attention-deficit hyperactivity disorder and their suppression by D-amphetamine.

PubMed

Clements, K M; Devonshire, I M; Reynolds, J N J; Overton, P G

2014-08-22

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by overactivity, impulsiveness and attentional problems, including an increase in distractibility. A structure that is intimately linked with distractibility is the superior colliculus (SC), a midbrain sensory structure which plays a particular role in the production of eye and head movements. Although others have proposed the involvement of such diverse elements as the frontal cortex and forebrain noradrenaline in ADHD, given the role of the colliculus in distractibility and the increased distractibility in ADHD, we have proposed that distractibility in ADHD arises due to collicular sensory hyper-responsiveness. To further investigate this possibility, we recorded the extracellular activity (multi-unit (MUA) and local field potential (LFP)) in the superficial visual layers of the SC in an animal model of ADHD, the New Zealand genetically hypertensive (GH) rat, in response to wholefield light flashes. The MUA and LFP peak amplitude and summed activity within a one-second time window post-stimulus were both significantly greater in GH rats than in Wistar controls, across the full range of stimulus intensities. Given that baseline firing rate did not differ between the strains, this suggests that the signal-to-noise ratio is elevated in GH animals. D-Amphetamine reduced the peak amplitude and summed activity of the multi-unit response in Wistar animals. It also reduced the peak amplitude and summed activity of the multi-unit response in GH animals, at higher doses bringing it down to levels that were equivalent to those of Wistar animals at baseline. The present results provide convergent evidence that a collicular dysfunction (sensory hyper-responsiveness) is present in ADHD, and that it may underlie the enhanced distractibility. In addition, D-amphetamine - a widely used treatment in ADHD - may have one of its loci of therapeutic action at the level of the

Salicylate-induced abnormal activity in the inferior colliculus of rats.

PubMed

Chen, G D; Jastreboff, P J

1995-02-01

The evaluation of the spontaneous activity of 471 units from the external nucleus of the IC revealed that salicylate induces an increase of the spontaneous activity and the emergence of a bursting type of activity longer than 4 spikes. For sharply tuned units, the affected cells were from the frequency range of 10-16 kHz, which corresponds to the behaviorally measured pitch of salicylate-induced tinnitus in rats. An exogenous calcium supplement, provided under the conditions shown to attenuate the behavioral manifestation of salicylate-induced tinnitus, abolished the modification of the spontaneous activity induced by salicylate. Finally, profound changes of activity were observed for cells not responding to contralateral sound. We propose that the observed long bursts of discharges represent tinnitus-related neuronal activity. The results are consistent with the hypothesis that GABA-mediated disinhibition is involved in the processing of tinnitus-related neuronal activity.

Inferior alveolar nerve block: Alternative technique.

PubMed

Thangavelu, K; Kannan, R; Kumar, N Senthil

2012-01-01

Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages.

Nonvisual influences on visual-information processing in the superior colliculus.

PubMed

Stein, B E; Jiang, W; Wallace, M T; Stanford, T R

2001-01-01

Although visually responsive neurons predominate in the deep layers of the superior colliculus (SC), the majority of them also receive sensory inputs from nonvisual sources (i.e. auditory and/or somatosensory). Most of these 'multisensory' neurons are able to synthesize their cross-modal inputs and, as a consequence, their responses to visual stimuli can be profoundly enhanced or depressed in the presence of a nonvisual cue. Whether response enhancement or response depression is produced by this multisensory interaction is predictable based on several factors. These include: the organization of a neuron's visual and nonvisual receptive fields; the relative spatial relationships of the different stimuli (to their respective receptive fields and to one another); and whether or not the neuron is innervated by a select population of cortical neurons. The response enhancement or depression of SC neurons via multisensory integration has significant survival value via its profound impact on overt attentive/orientation behaviors. Nevertheless, these multisensory processes are not present at birth, and require an extensive period of postnatal maturation. It seems likely that the sensory experiences obtained during this period play an important role in crafting the processes underlying these multisensory interactions.

Non-inferiority trials: are they inferior? A systematic review of reporting in major medical journals

PubMed Central

Morris, Tim P; Fielding, Katherine; Carpenter, James R; Phillips, Patrick P J

2016-01-01

Objective To assess the adequacy of reporting of non-inferiority trials alongside the consistency and utility of current recommended analyses and guidelines. Design Review of randomised clinical trials that used a non-inferiority design published between January 2010 and May 2015 in medical journals that had an impact factor >10 (JAMA Internal Medicine, Archives Internal Medicine, PLOS Medicine, Annals of Internal Medicine, BMJ, JAMA, Lancet and New England Journal of Medicine). Data sources Ovid (MEDLINE). Methods We searched for non-inferiority trials and assessed the following: choice of non-inferiority margin and justification of margin; power and significance level for sample size; patient population used and how this was defined; any missing data methods used and assumptions declared and any sensitivity analyses used. Results A total of 168 trial publications were included. Most trials concluded non-inferiority (132; 79%). The non-inferiority margin was reported for 98% (164), but less than half reported any justification for the margin (77; 46%). While most chose two different analyses (91; 54%) the most common being intention-to-treat (ITT) or modified ITT and per-protocol, a large number of articles only chose to conduct and report one analysis (65; 39%), most commonly the ITT analysis. There was lack of clarity or inconsistency between the type I error rate and corresponding CIs for 73 (43%) articles. Missing data were rarely considered with (99; 59%) not declaring whether imputation techniques were used. Conclusions Reporting and conduct of non-inferiority trials is inconsistent and does not follow the recommendations in available statistical guidelines, which are not wholly consistent themselves. Authors should clearly describe the methods used and provide clear descriptions of and justifications for their design and primary analysis. Failure to do this risks misleading conclusions being drawn, with consequent effects on clinical practice. PMID:27855102

Maternal Gestational Androgen Levels in Female Marmosets (Callithrix geoffroyi) Vary Across Trimesters but Do Not Vary With the Sex Ratio of Litters

PubMed Central

French, Jeffrey A.; Smith, Adam S.; Birnie, Andrew K.

2009-01-01

Maternal hormones can dramatically modify offspring phenotypes via organizational actions on morphological and behavioral development. In placental mammals, there is the possibility that some portion of hormones in maternal circulation may be derived from fetal origin. We tested the possibility that maternal androgens in pregnant female marmosets reflected, in part, contributions from male fetuses by comparing levels of urinary androgens across pregnancy in females carrying varying numbers of male offspring. We monitored urinary androgen excretion in 18 pregnancies from five female white-faced marmosets (Callithrix geoffroyi). Androgen levels rose significantly in the first trimester of pregnancy, reached a peak in the middle of the second trimester, and then declined gradually until parturition. At no point in pregnancy were levels of urinary androgens higher in females carrying litters that had 50% or more males than females carrying litters that were less than 50% male. Levels of maternal androgens were not associated with litter size, the number of males in the litter, or with the proportion of the litter that was male. The high levels of androgen in pregnant females are therefore likely of strictly maternal origin, and any modification of fetal growth and development can be considered a ‘maternal effect’. PMID:19646445

Reversal learning in gonadectomized marmosets with and without hormone replacement: are males more sensitive to punishment?

PubMed

LaClair, Matthew; Lacreuse, Agnès

2016-05-01

This study examined sex differences in executive function in middle-aged gonadectomized marmosets (Callithrix jacchus) with or without hormonal replacement. We tested ten castrated male (mean age 5.5 years) marmosets treated with testosterone cypionate (T, n = 5) or vehicle (n = 5) on Reversal Learning, which contributes to cognitive flexibility, and the Delayed Response task, measuring working memory. Their performance was compared to that of 11 ovariectomized females (mean age = 3.7 years) treated with Silastic capsules filled with 17-β estradiol (E2, n = 6) or empty capsules (n = 5), previously tested on the same tasks (Lacreuse et al. in J Neuroendocrinol 26:296-309, 2014. doi: 10.1111/jne.12147). Behavioral observations were conducted daily. Females exhibited more locomotor behaviors than males. Males and females did not differ in the number of trials taken to reach criterion on the reversals, but males had significantly longer response latencies, regardless of hormone replacement. They also had a greater number of refusals than females. Additionally, both control and T-treated males, but not females, had slower responses on incorrect trials, suggesting that males were making errors due to distraction, lack of motivation or uncertainty. Furthermore, although both males and females had slower responding following an incorrect compared to a correct trial, the sex difference in response latencies was disproportionally large following an incorrect trial. No sex difference was found in the Delayed Response task. Overall, slower response latencies in males than females during Reversal Learning, especially during and following an incorrect trial, may reflect greater sensitivity to punishment (omission of reward) and greater performance monitoring in males, compared to females. Because these differences occurred in gonadectomized animals and regardless of hormone replacement, they may be organized early in life.

Visual motion integration by neurons in the middle temporal area of a New World monkey, the marmoset

PubMed Central

Solomon, Selina S; Tailby, Chris; Gharaei, Saba; Camp, Aaron J; Bourne, James A; Solomon, Samuel G

2011-01-01

Abstract The middle temporal area (MT/V5) is an anatomically distinct region of primate visual cortex that is specialized for the processing of image motion. It is generally thought that some neurons in area MT are capable of signalling the motion of complex patterns, but this has only been established in the macaque monkey. We made extracellular recordings from single units in area MT of anaesthetized marmosets, a New World monkey. We show through quantitative analyses that some neurons (35 of 185; 19%) are capable of signalling pattern motion (‘pattern cells’). Across several dimensions, the visual response of pattern cells in marmosets is indistinguishable from that of pattern cells in macaques. Other neurons respond to the motion of oriented contours in a pattern (‘component cells’) or show intermediate properties. In addition, we encountered a subset of neurons (22 of 185; 12%) insensitive to sinusoidal gratings but very responsive to plaids and other two-dimensional patterns and otherwise indistinguishable from pattern cells. We compared the response of each cell class to drifting gratings and dot fields. In pattern cells, directional selectivity was similar for gratings and dot fields; in component cells, directional selectivity was weaker for dot fields than gratings. Pattern cells were more likely to have stronger suppressive surrounds, prefer lower spatial frequencies and prefer higher speeds than component cells. We conclude that pattern motion sensitivity is a feature of some neurons in area MT of both New and Old World monkeys, suggesting that this functional property is an important stage in motion analysis and is likely to be conserved in humans. PMID:21946851

Complications of inferior vena cava filters.

PubMed

Sella, David M; Oldenburg, W Andrew

2013-03-01

With the introduction of retrievable inferior vena cava filters, the number being placed for protection from pulmonary embolism is steadily increasing. Despite this increased usage, the true incidence of complications associated with inferior vena cava filters is unknown. This article reviews the known complications associated with these filters and suggests recommendations and techniques for inferior vena cava filter removal. Copyright © 2013. Published by Elsevier Inc.

Inferior alveolar nerve block: Alternative technique

PubMed Central

Thangavelu, K.; Kannan, R.; Kumar, N. Senthil

2012-01-01

Background: Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. Aim and Objective: The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. Materials and Methods: This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. Conclusion: This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages. PMID:25885503

The central role of recognition in auditory perception: a neurobiological model.

PubMed

McLachlan, Neil; Wilson, Sarah

2010-01-01

The model presents neurobiologically plausible accounts of sound recognition (including absolute pitch), neural plasticity involved in pitch, loudness and location information integration, and streaming and auditory recall. It is proposed that a cortical mechanism for sound identification modulates the spectrotemporal response fields of inferior colliculus neurons and regulates the encoding of the echoic trace in the thalamus. Identification involves correlation of sequential spectral slices of the stimulus-driven neural activity with stored representations in association with multimodal memories, verbal lexicons, and contextual information. Identities are then consolidated in auditory short-term memory and bound with attribute information (usually pitch, loudness, and direction) that has been integrated according to the identities' spectral properties. Attention to, or recall of, a particular identity will excite a particular sequence in the identification hierarchies and so lead to modulation of thalamus and inferior colliculus neural spectrotemporal response fields. This operates as an adaptive filter for identities, or their attributes, and explains many puzzling human auditory behaviors, such as the cocktail party effect, selective attention, and continuity illusions.

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.

Regulatory Scientific Advice on Non-Inferiority Drug Trials

PubMed Central

Knol, Mirjam J.; Klungel, Olaf H.; Gispen-De Wied, Christine C.; de Boer, Antonius; Hoes, Arno W.; Leufkens, Hubert G.; Mantel-Teeuwisse, Aukje K.

2013-01-01

The active-controlled trial with a non-inferiority design has gained popularity in recent years. However, non-inferiority trials present some methodological challenges, especially in determining the non-inferiority margin. Regulatory guidelines provide some general statements on how a non-inferiority trial should be conducted. Moreover, in a scientific advice procedure, regulators give companies the opportunity to discuss critical trial issues prior to the start of the trial. The aim of this study was to identify potential issues that may benefit from more explicit guidance by regulators. To achieve this, we collected and analyzed questions about non-inferiority trials posed by applicants for scientific advice in Europe in 2008 and 2009, as well as the responses given by the European Medicines Agency (EMA). In our analysis we included 156 final letters of advice from 2008 and 2009, addressed to 94 different applicants (manufacturers). Our analysis yielded two major findings: (1) applicants frequently asked questions ‘whether’ and ‘how’ to conduct a non-inferiority trial, 26% and 74%, respectively, and (2) the EMA regulators seem mainly concerned about the choice of the non-inferiority margin in non-inferiority trials (36% of total regulatory answers). In 40% of the answers, the EMA recommended using a stricter margin, and in 10% of the answers regarding non-inferiority margins, the EMA questioned the justification of the proposed non-inferiority margin. We conclude that there are still difficulties in selecting the appropriate methodology for non-inferiority trials. Straightforward and harmonized guidance regarding non-inferiority trials is required, for example on whether it is necessary to conduct such a trial and how the non-inferiority margin is determined. It is unlikely that regulatory guidelines can cover all therapeutic areas; therefore, in some cases regulatory scientific advice may be used as an opportunity for tailored advice. PMID:24040346

Comparative study of unilateral versus bilateral inferior oblique recession/anteriorization in unilateral inferior oblique overaction.

PubMed

Mostafa, Attiat M; Kassem, Rehab R

2018-05-01

To compare the effect of, and the rate of subsequent development of iatrogenic antielevation syndrome after, unilateral versus bilateral inferior oblique graded recession-anteriorization to treat unilateral inferior oblique overaction. Thirty-four patients with unilateral inferior oblique overaction were included in a randomized prospective study. Patients were equally divided into 2 groups. Group UNI underwent unilateral, group BI bilateral, inferior oblique graded recession-anteriorization. A successful outcome was defined as orthotropia, or within 2 ∆ of a residual hypertropia, in the absence of signs of antielevation syndrome, residual inferior oblique overaction, V-pattern, dissociated vertical deviation, or ocular torticollis. A successful outcome was achieved in 11 (64.7%) and 13 (76.5%) patients in groups UNI and BI, respectively (p = 0.452). Antielevation syndrome was diagnosed as the cause of surgical failure in 6 (35.3%) and 2 (11.8%) patients, in groups UNI and BI, respectively (p = 0.106). The cause of surgical failure in the other 2 patients in group BI was due to persistence of ocular torticollis and hypertropia in a patient with superior oblique palsy and a residual V-pattern and hypertropia in the other patient. The differences between unilateral and bilateral inferior oblique graded recession-anteriorization are insignificant. Unilateral surgery has a higher tendency for the subsequent development of antielevation syndrome. Bilateral surgery may still become complicated by antielevation syndrome, although at a lower rate. In addition, bilateral surgery had a higher rate of undercorrection. Further studies on a larger sample are encouraged.

Neurophysiological analysis of echolocation in bats

NASA Technical Reports Server (NTRS)

Suga, N.

1972-01-01

An analysis of echolocation and signal processing in brown bats is presented. Data cover echo detection, echo ranging, echolocalization, and echo analysis. Efforts were also made to identify the part of the brain that carries out the most essential processing function for echolocation. Results indicate the inferior colliculus and the auditory nuclei function together to process this information.

Superior versus inferior Ahmed glaucoma valve implantation.

PubMed

Pakravan, Mohammad; Yazdani, Shahin; Shahabi, Camelia; Yaseri, Mehdi

2009-02-01

To compare the efficacy and safety of Ahmed glaucoma valve (AGV) (New World Medical Inc., Rancho Cucamonga, CA) implantation in the superior versus inferior quadrants. Prospective parallel cohort study. A total of 106 eyes of 106 patients with refractory glaucoma. Consecutive patients with refractory glaucoma underwent AGV implantation in the superior or inferior quadrants. Main outcome measures included intraocular pressure (IOP) and rate of complications. Other outcome measures included best corrected visual acuity (BCVA), number of glaucoma medications, and success rate (defined as at least 30% IOP reduction and 5inferior quadrants, respectively. Baseline characteristics were comparable in the study groups, except for preoperative IOP, which was higher in the superior group (P = 0.01). Patients were followed for a mean period of 10.6+/-8.49 months and 10.58+/-6.75 months in the superior and inferior groups, respectively (P = 0.477). BCVA was comparable between the groups at all postoperative visits (P>0.122). After 1 year, statistically significant but comparable IOP reduction from baseline (P<0.001) was achieved in both groups (47.0%+/-27.2% and 43.0%+/-24.5% reduction for superior and inferior groups, respectively, P = 0.725). The mean number of glaucoma medications was comparable after 1 year (1.3+/-1.2 vs. 1.9+/-0.8 for superior and inferior implants, respectively, P = 0.256). Success rates were also similar at 1 year: 27 eyes (81.8%) versus 20 eyes (95.2%) for superior and inferior implants, respectively (P = 0.227). However, the overall rate of complications, such as implant exposure necessitating removal, cosmetically unappealing appearance, and endophthalmitis, was higher in the inferior group: 12 eyes (25

Common Marmosets (Callithrix jacchus) as a Nonhuman Primate Model To Assess the Virulence of Eastern Equine Encephalitis Virus Strains▿

PubMed Central

Adams, A. Paige; Aronson, Judith F.; Tardif, Suzette D.; Patterson, Jean L.; Brasky, Kathleen M.; Geiger, Robert; de la Garza, Melissa; Carrion, Ricardo; Weaver, Scott C.

2008-01-01

Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral disease in North America (NA) and is a potential biological weapon. However, genetically and antigenically distinct strains from South America (SA) have seldom been associated with human disease or mortality despite serological evidence of infection. Because mice and other small rodents do not respond differently to the NA versus SA viruses like humans, we tested common marmosets (Callithrix jacchus) by using intranasal infection and monitoring for weight loss, fever, anorexia, depression, and neurologic signs. The NA EEEV-infected animals either died or were euthanized on day 4 or 5 after infection due to anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy and survived. The SA EEEV-infected animals developed peak viremia titers of 2.8 to 3.1 log10 PFU/ml on day 2 or 4 after infection, but there was no detectable viremia in the NA EEEV-infected animals. In contrast, virus was detected in the brain, liver, and muscle of the NA EEEV-infected animals at the time of euthanasia or death. Similar to the brain lesions described for human EEE, the NA EEEV-infected animals developed meningoencephalitis in the cerebral cortex with some perivascular hemorrhages. The findings of this study identify the common marmoset as a useful model of human EEE for testing antiviral drugs and vaccine candidates and highlight their potential for corroborating epidemiological evidence that some, if not all, SA EEEV strains are attenuated for humans. PMID:18614636

Gene targeting and subsequent site-specific transgenesis at the β-actin (ACTB) locus in common marmoset embryonic stem cells.

PubMed

Shiozawa, Seiji; Kawai, Kenji; Okada, Yohei; Tomioka, Ikuo; Maeda, Takuji; Kanda, Akifumi; Shinohara, Haruka; Suemizu, Hiroshi; James Okano, Hirotaka; Sotomaru, Yusuke; Sasaki, Erika; Okano, Hideyuki

2011-09-01

Nonhuman primate embryonic stem (ES) cells have vast promise for preclinical studies. Genetic modification in nonhuman primate ES cells is an essential technique for maximizing the potential of these cells. The common marmoset (Callithrix jacchus), a nonhuman primate, is expected to be a useful transgenic model for preclinical studies. However, genetic modification in common marmoset ES (cmES) cells has not yet been adequately developed. To establish efficient and stable genetic modifications in cmES cells, we inserted the enhanced green fluorescent protein (EGFP) gene with heterotypic lox sites into the β-actin (ACTB) locus of the cmES cells using gene targeting. The resulting knock-in ES cells expressed EGFP ubiquitously under the control of the endogenous ACTB promoter. Using inserted heterotypic lox sites, we demonstrated Cre recombinase-mediated cassette exchange (RMCE) and successfully established a monomeric red fluorescent protein (mRFP) knock-in cmES cell line. Further, a herpes simplex virus-thymidine kinase (HSV-tk) knock-in cmES cell line was established using RMCE. The growth of tumor cells originating from the cell line was significantly suppressed by the administration of ganciclovir. Therefore, the HSV-tk/ganciclovir system is promising as a safeguard for stem cell therapy. The stable and ubiquitous expression of EGFP before RMCE enables cell fate to be tracked when the cells are transplanted into an animal. Moreover, the creation of a transgene acceptor locus for site-specific transgenesis will be a powerful tool, similar to the ROSA26 locus in mice.

Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks

PubMed Central

Soper, Colin; Wicker, Evan; Kulick, Catherine V.; N’Gouemo, Prosper; Forcelli, Patrick A.

2016-01-01

Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy. PMID:26721319

Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks.

PubMed

Soper, Colin; Wicker, Evan; Kulick, Catherine V; N'Gouemo, Prosper; Forcelli, Patrick A

2016-03-01

Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Inferior sinus venosus defects: anatomic features and echocardiographic correlates.

PubMed

Plymale, Jennifer; Kolinski, Kellen; Frommelt, Peter; Bartz, Peter; Tweddell, James; Earing, Michael G

2013-02-01

Inferior sinus venosus defects (SVDs) are rare imperfections located in the inferior portion of the atrial septum, leading to an overriding inferior vena cava (IVC) and an interatrial connection. These defects have increased risk of anomalous pulmonary venous return (PAPVR) and often are confused with secundum atrial septal defects (ASDs) with inferior extension. The authors sought to review their experience with inferior SVDs and to establish at their institution an echocardiographic definition that differentiates inferior SVDs from secundum ASDs with inferior extension. The study identified 161 patients 1.5 to 32 years of age who had undergone repair of a secundum ASD with inferior extension or inferior SVD over the preceding 10 years. All surgical notes, preoperative transthoracic echocardiograms (TTEs), and preoperative transesophageal echocardiograms (TEEs) were reviewed. Based on the surgical notes, 147 patients were classified as having a secundum ASD (147/161, 91 %) and 14 patients (9 %) as having an inferior SVD. The study identified PAPVR in 7 % (1/14) of the patients with inferior SVDs and 3.5 % (5/14) of the patients with secundum ASDs. Surgical diagnosis and preoperative TTE correlated for 143 (89 %) of the 161 patients. Using a strict anatomic and echocardiographic definition with a blinded observer, the majority of the defects (14/18, 78 %) were reclassified correctly after review of their TTE images, and 100 % of the defects were correctly reclassified after TEE image review. Accurate diagnosis of inferior SVDs remains challenging. The data from this study demonstrate that use of a strict anatomic and echocardiographic definition (a defect that originates in the mouth of the IVC and continues into the inferoposterior border of the left atrium, leaving no residual atrial septal tissue at the inferior margin) allows for accurate differentiation between secundum ASDs with inferior extension and inferior SVDs. This differentiation is extremely important

Parturition Signaling by Visual Cues in Female Marmosets (Callithrix jacchus)

PubMed Central

Moreira, Laís Alves Antonio; de Oliveira, Danilo Gustavo Rodrigues; de Sousa, Maria Bernardete Cordeiro; Pessoa, Daniel Marques Almeida

2015-01-01

New World monkeys have polymorphic color vision, in which all males and some females are dichromats, while most females are trichromats. There is little consensus about which selective pressures fashioned primate color vision, although detection of food, mates and predators has been hypothesized. Behavioral evidence shows that males from different species of Neotropical primates seem to perceive the timing of female conception and gestation, although, no signals fulfilling this function have been identified. Therefore, we used visual models to test the hypothesis that female marmosets show chromatic and/or achromatic cues that may indicate the time of parturition for male and female conspecifics. By recording the reflectance spectra of female marmosets’ (Callithrix jacchus) sexual skin, and running chromatic and achromatic discrimination models, we found that both variables fluctuate during the weeks that precede and succeed parturition, forming “U” and inverted “U” patterns for chromatic and achromatic contrast, respectively. We suggest that variation in skin chroma and luminance might be used by female helpers and dominant females to identify the timing of birth, while achromatic variations may be used as clues by potential fathers to identify pregnancy stage in females and prepare for paternal burdens as well as to detect oestrus in the early post-partum period. PMID:26047350

Cross-correlated and oscillatory visual responses of superficial-layer and tecto-reticular neurones in cat superior colliculus.

PubMed

Chabli, A; Guitton, D; Fortin, S; Molotchnikoff, S

2000-03-01

The present study examined, in the superior colliculus (SC) of anaesthetised cats, the functional connectivity between superficial-layer neurones (SLNs) and tectoreticular neurones (TRNs: collicular output cells). TRNs were antidromically identified by electrical stimulation of the predorsal bundle. The auto- and cross-correlation histograms of visual responses of both types of neurones were recorded and analysed. A delayed, sharp peak in cross-correlograms allowed us to verify whether SLN and TRN cells were coupled; in addition, oscillatory activities were compared to verify if rhythmic responses of SLN sites were transmitted to TRN sites. We found that oscillatory activity was rarely observed in spontaneous activity of superficial (1/74) and TRN sites (1/48). Moving light bars induced oscillation in 31% (23/74) of the superficial-layer and in 23% (11/48) of the TRN sites. The strength of the rhythmic responses was determined by specific ranges of stimulus velocity in 83% (19/23) and 64% (7/11) of oscillating SLN and TRN sites, respectively. Frequencies of oscillations ranged between 5 and 125 Hz and were confined, for 53% of the cells, to the 5-20 Hz band. Thus, the band-width of frequencies of the stimulus-related oscillations in the superior colliculus was broader than the gamma range. Analysis of cross-correlation histograms revealed a significant predominant peak with a mean delay of 2.7+/-0.9 ms in 46% (17/37) of SLN-TRN pairs. Most correlated SLN-TRN pairs (88%: 15/17) had superimposed receptive fields, suggesting they were functionally interconnected. However, individual oscillatory frequencies of correlated and oscillatory SLN and TRN cells were never the same (0/8). Together, these results suggest that the neurones in collicular superficial layer contact TRNs and, consequently, support the idea that the superficial layers contribute to collicular outputs producing eye- and head-orienting movements.

Dental remains of cebid platyrrhines from the earliest late Miocene of Western Amazonia, Peru: Macroevolutionary implications on the extant capuchin and marmoset lineages.

PubMed

Marivaux, Laurent; Adnet, Sylvain; Altamirano-Sierra, Ali J; Pujos, François; Ramdarshan, Anusha; Salas-Gismondi, Rodolfo; Tejada-Lara, Julia V; Antoine, Pierre-Olivier

2016-11-01

Undoubted fossil Cebidae have so far been primarily documented from the late middle Miocene of Colombia, the late Miocene of Brazilian Amazonia, the early Miocene of Peruvian Amazonia, and very recently from the earliest Miocene of Panama. The evolutionary history of cebids is far from being well-documented, with notably a complete blank in the record of callitrichine stem lineages until and after the late middle Miocene (Laventan SALMA). Further documenting their evolutionary history is therefore of primary importance. Recent field efforts in Peruvian Amazonia (Contamana area, Loreto Department) have allowed for the discovery of an early late Miocene (ca. 11 Ma; Mayoan SALMA) fossil primate-bearing locality (CTA-43; Pebas Formation). In this study, we analyze the primate material, which consists of five isolated teeth documenting two distinct Cebidae: Cebus sp., a medium-sized capuchin (Cebinae), and Cebuella sp., a tiny marmoset (Callitrichinae). Although limited, this new fossil material of platyrrhines contributes to documenting the post-Laventan evolutionary history of cebids, and besides testifies to the earliest occurrences of the modern Cebuella and Cebus/Sapajus lineages in the Neotropics. Regarding the evolutionary history of callitrichine marmosets, the discovery of an 11 Ma-old fossil representative of the modern Cebuella pushes back by at least 6 Ma the age of the Mico/Cebuella divergence currently proposed by molecular biologists (i.e., ca. 4.5 Ma). This also extends back to > 11 Ma BP the divergence between Callithrix and the common ancestor (CA) of Mico/Cebuella, as well as the divergence between the CA of marmosets and Callimico (Goeldi's callitrichine). This discovery from Peruvian Amazonia implies a deep evolutionary root of the Cebuella lineage in the northwestern part of South America (the modern western Amazon basin), slightly before the recession of the Pebas mega-wetland system (PMWS), ca. 10.5 Ma, and well-before the subsequent

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

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys

PubMed Central

Fleuriet, Jérome; Walton, Mark M. G.; Ono, Seiji; Mustari, Michael J.

2016-01-01

Purpose Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. Methods We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. Results We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Conclusions Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract PMID:27309621

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys.

PubMed

Fleuriet, Jérome; Walton, Mark M G; Ono, Seiji; Mustari, Michael J

2016-06-01

Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract.

[Contralateral Recession of the Inferior Oblique Muscle in Grave's Disease Patients with Mild M. rectus inferior fibrosis].

PubMed

Eckstein, A; Raczynski, S; Dekowski, D; Esser, J

2015-10-01

The aim of this study was to evaluate the dose effect and the resulting binocular single vision for inferior oblique muscle recession in patients with Grave's orbitopathy. The evaluation covered all patients (n = 13) between 2010-2013 treated with recession of the inferior oblique muscle for vertical deviation caused by inferior fibrosis of the contralateral eye. The inclusion criterion was a small vertical squint angle with excyclotorsion. The corrected vertical squint angle was 3.75° [7 pdpt] (median, min 1.5° [3 pdpt], max 8° [16 pdpt]) in primary position and 5.5° in adduction [11pdpt] (median, min 3°[6 pdpt], max 9°[18pdpt]). Excyclotorsion was 4° [8 pdpt] (median, min 1° [2 pdpt], max 9° [18 pdpt]). Elevation was only slightly impaired and the side difference was 5° (median). The recession distance was preoperatively determined: 0.5° squint angle reduction per mm recession distance (calculation from patients who received surgery before 2010). Inferior oblique recession generated a good field of binocular single vision (BSV) for all patients. All patients reached BSV in the central area (20°) and within 30° of downgaze. Sixty nine percent of the patients were completely diplopia free in downgaze. Diplopia persisted in more than half of the patients in up gaze outside 15°. Squint reduction was 0.5° [1 pdpt] [0.45-0.67]/per mm recession distance in primary position and 0.65° [1.3 pdpt] [0.55-0.76]/per mm for the vertical deviation in adduction. Excyclotorsion was reduced to ≤ 2° in 77 % of the patients. Inferior oblique muscle recession can be very successfully performed on the contralateral eye in patients with mild inferior rectus muscle fibrosis. Surgery at the contralateral yoke muscle prevents the risk of overeffect with resulting diplopia in downgaze, which could occur if small distance recession had been performed at the inferior rectus muscle. An overeffect in relation to inferior oblique recession will only

Preceding weak noise sharpens the frequency tuning and elevates the response threshold of the mouse inferior collicular neurons through GABAergic inhibition.

PubMed

Wang, Xin; Jen, Philip H-S; Wu, Fei-Jian; Chen, Qi-Cai

2007-09-05

In acoustic communication, animals must extract biologically relevant signals that are embedded in noisy environment. The present study examines how weak noise may affect the auditory sensitivity of neurons in the central nucleus of the mouse inferior colliculus (IC) which receives convergent excitatory and inhibitory inputs from both lower and higher auditory centers. Specifically, we studied the frequency sensitivity and minimum threshold of IC neurons using a pure tone probe and a weak white noise masker under forward masking paradigm. For most IC neurons, probe-elicited response was decreased by a weak white noise that was presented at a specific gap (i.e. time window). When presented within this time window, weak noise masking sharpened the frequency tuning curve and increased the minimum threshold of IC neurons. The degree of weak noise masking of these two measurements increased with noise duration. Sharpening of the frequency tuning curve and increasing of the minimum threshold of IC neurons during weak noise masking were mostly mediated through GABAergic inhibition. In addition, sharpening of frequency tuning curve by the weak noise masker was more effective at the high than at low frequency limb. These data indicate that in the real world the ambient noise may improve frequency sensitivity of IC neurons through GABAergic inhibition while inevitably decrease the frequency response range and sensitivity of IC neurons.

Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset.

PubMed

Chen, Zhe; Bao, Linlin; Chen, Cong; Zou, Tingting; Xue, Ying; Li, Fengdi; Lv, Qi; Gu, Songzhi; Gao, Xiaopan; Cui, Sheng; Wang, Jianmin; Qin, Chuan; Jin, Qi

2017-06-15

Middle East respiratory syndrome coronavirus (MERS-CoV) infection in humans is highly lethal, with a fatality rate of 35%. New prophylactic and therapeutic strategies to combat human infections are urgently needed. We isolated a fully human neutralizing antibody, MCA1, from a human survivor. The antibody recognizes the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4). To our knowledge, this study is the first to report a human neutralizing monoclonal antibody that completely inhibits MERS-CoV replication in common marmosets. Monotherapy with MCA1 represents a potential alternative treatment for human infections with MERS-CoV worthy of evaluation in clinical settings. © Crown copyright 2017.

Modeling the Value of Strategic Actions in the Superior Colliculus

PubMed Central

Thevarajah, Dhushan; Webb, Ryan; Ferrall, Christopher; Dorris, Michael C.

2009-01-01

In learning models of strategic game play, an agent constructs a valuation (action value) over possible future choices as a function of past actions and rewards. Choices are then stochastic functions of these action values. Our goal is to uncover a neural signal that correlates with the action value posited by behavioral learning models. We measured activity from neurons in the superior colliculus (SC), a midbrain region involved in planning saccadic eye movements, while monkeys performed two saccade tasks. In the strategic task, monkeys competed against a computer in a saccade version of the mixed-strategy game ”matching-pennies”. In the instructed task, saccades were elicited through explicit instruction rather than free choices. In both tasks neuronal activity and behavior were shaped by past actions and rewards with more recent events exerting a larger influence. Further, SC activity predicted upcoming choices during the strategic task and upcoming reaction times during the instructed task. Finally, we found that neuronal activity in both tasks correlated with an established learning model, the Experience Weighted Attraction model of action valuation (Camerer and Ho, 1999). Collectively, our results provide evidence that action values hypothesized by learning models are represented in the motor planning regions of the brain in a manner that could be used to select strategic actions. PMID:20161807

Grooming as a reward? Social function of grooming between females in cooperatively breeding marmosets

PubMed Central

LAZARO-PEREA, CRISTINA; DE FÁTIMA ARRUDA, MARIA; SNOWDON, CHARLES T.

2006-01-01

Classical models of grooming predict that subordinate primates will direct grooming towards dominants to receive coalitionary support from them. In contrast, recent reviews suggest that grooming asymmetries can change with social system and ecological conditions and should reflect asymmetries in services provided by different members of the dyad. We studied grooming patterns between females in six wild groups of common marmosets, Callithrix jacchus, to investigate the relation between social structure and grooming between females in a cooperatively breeding species. We observed grooming frequently and consistently in all study groups. Breeding females groomed nonbreeding females more than vice versa, and grooming between breeding and nonbreeding females was not related to agonistic behaviour. Our results provide some support to the hypothesis that grooming asymmetries are related to differences in services provided by different group members. We suggest that, in cooperatively breeding systems, breeding females may use grooming as an incentive for helper females to stay in the group. PMID:17237884

Infant feeding with soy formula milk: effects on puberty progression, reproductive function and testicular cell numbers in marmoset monkeys in adulthood.

PubMed

Tan, Karen A L; Walker, Marion; Morris, Keith; Greig, Irene; Mason, J Ian; Sharpe, Richard M

2006-04-01

This marmoset study addresses concerns about feeding human male infants with soy formula milk (SFM). From age 4 to 5 days, seven male co-twin sets were fed standard formula milk (SMA) or SFM for 5-6 weeks; blood samples were subsequently collected at 10-week intervals. Testes from co-twins killed at 120-138 weeks were fixed for cell counts. SFM- and SMA-fed twins showed normal weight gain; puberty started and progressed normally, based on blood testosterone measurements. Body weight, organ weights (prostate, seminal vesicles, pituitary, thymus and spleen) and penis length were comparable in co-twins. All SMA- and 6/7 SFM-fed males were fertile. Unexpectedly, testis weight (P = 0.041), Sertoli (P = 0.025) and Leydig cell (P = 0.026) numbers per testis were consistently increased in SFM-fed co-twins; the increase in Leydig cell numbers was most marked in males with consistently low-normal testosterone levels. Seminiferous epithelium volume per tubule showed a less consistent, non-significant increase in SFM-fed males; raised germ cell numbers per testis, probably due to increased Sertoli cells, conceivably resulted in larger testes. Average lumen size, although greater in SFM-fed group, was inconsistent between co-twins and the difference was not significant. Infant feeding with SFM has no gross adverse reproductive effects in male marmosets, though it alters testis size and cell composition, and there is consistent, if indirect, evidence for possible 'compensated Leydig cell failure'. Similar and perhaps larger changes likely occur in adult men who were fed SFM as infants.

Functional Organization and Dynamic Activity in the Superior Colliculus of the Echolocating Bat, Eptesicus fuscus.

PubMed

Wohlgemuth, Melville J; Kothari, Ninad B; Moss, Cynthia F

2018-01-03

Sensory-guided behaviors require the transformation of sensory information into task-specific motor commands. Prior research on sensorimotor integration has emphasized visuomotor processes in the context of simplified orienting movements in controlled laboratory tasks rather than an animal's more complete, natural behavioral repertoire. Here, we conducted a series of neural recording experiments in the midbrain superior colliculus (SC) of echolocating bats engaged in a sonar target-tracking task that invoked dynamic active sensing behaviors. We hypothesized that SC activity in freely behaving animals would reveal dynamic shifts in neural firing patterns within and across sensory, sensorimotor, and premotor layers. We recorded neural activity in the SC of freely echolocating bats (three females and one male) and replicated the general trends reported in other species with sensory responses in the dorsal divisions and premotor activity in ventral divisions of the SC. However, within this coarse functional organization, we discovered that sensory and motor neurons are comingled within layers throughout the volume of the bat SC. In addition, as the bat increased pulse rate adaptively to increase resolution of the target location with closing distance, the activity of sensory and vocal premotor neurons changed such that auditory response times decreased, and vocal premotor lead times shortened. This finding demonstrates that SC activity can be modified dynamically in concert with adaptive behaviors and suggests that an integrated functional organization within SC laminae supports rapid and local integration of sensory and motor signals for natural, adaptive behaviors. SIGNIFICANCE STATEMENT Natural sensory-guided behaviors involve the rapid integration of information from the environment to direct flexible motor actions. The vast majority of research on sensorimotor integration has used artificial stimuli and simplified behaviors, leaving open questions about nervous

Formation of infectious dengue virus-antibody immune complex in vivo in marmosets (Callithrix jacchus) after passive transfer of anti-dengue virus monoclonal antibodies and infection with dengue virus.

PubMed

Moi, Meng Ling; Ami, Yasushi; Shirai, Kenji; Lim, Chang-Kweng; Suzaki, Yuriko; Saito, Yuka; Kitaura, Kazutaka; Saijo, Masayuki; Suzuki, Ryuji; Kurane, Ichiro; Takasaki, Tomohiko

2015-02-01

Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells. © The American Society of Tropical Medicine and Hygiene.

Training in Methods in Computational Neuroscience

DTIC Science & Technology

1989-11-14

inferior colliculus served as inputs to a sheet of 100 cells within the medial geniculate body where combination sensitivity is first observed. Inputs from...course is for advanced graduate students and postdoctoral fellows in neurobiology , physics, electrical engineering, computer science and psychology...Research Code 1142BI 800 N. Quincy St Arlington, VA 22217-5000 Paul Adams Department of Neurobiology SUNY, Stony Brook Graduate Biology Building 576

Endovascular management of inferior vena cava filter thrombotic occlusion.

PubMed

Branco, Bernardino C; Montero-Baker, Miguel F; Espinoza, Eduardo; Gamero, Maria; Zea-Vera, Rodrigo; Labropoulos, Nicos; Leon, Luis R

2018-01-01

Objective Inferior vena cava occlusion is a potentially life-threatening complication related to caval filters. We present our experience with filter-induced inferior vena cava occlusion in order to assess the feasibility, safety, and effectiveness of endovascular management. Methods A retrospective review of all patients undergoing inferior vena cava filter placement over a 60-month study period was performed. From this cohort, a total of 10 cases of inferior vena cava occlusion after filter placement were identified. Demographics, clinical data, procedures, and outcomes were extracted. Patients were followed to the last clinic visit or until they died. Results One-hundred eighty filters were placed by our group practice during the study period. Of those, a total of 10 patients were identified. Overall, there were 7 males; the mean age was 57.1 years (25-78 years). The median time between inferior vena cava filter placement and filter occlusion was 105 days (range 5-4745 days). All patients were clinically symptomatic at the time of their presentation. Nine out of 10 patients were successfully managed endovascularly. Trellis™-8 thrombectomy was the most common endovascular strategy performed ( n = 9). Four patients had balloon angioplasty, two of those with stent placement for chronically occluded inferior vena cava/iliac veins. No thromboembolic complications developed during a median follow-up period of 233 days (range 4-1083 days). Conclusions Endovascular management of inferior vena cava occlusion is feasible, safe, and effective in decreasing thrombus burden in the presence of an inferior vena cava filter. Further studies evaluating long-term inferior vena cava patency and optimal surveillance regimen after endovascular management of filter-related inferior vena cava occlusion are warranted.

Experimental Respiratory Infection of Marmosets (Callithrix jacchus) With Ebola Virus Kikwit.

PubMed

Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Nunez, Alejandro; Salguero, Francisco J; Lever, Mark S

2015-10-01

Ebola virus (EBOV) causes a highly infectious and lethal hemorrhagic fever in primates with high fatality rates during outbreaks and EBOV may be exploited as a potential biothreat pathogen. There is therefore a need to develop and license appropriate medical countermeasures against this virus. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess vaccines or therapies against EBOV disease (EVD), initial susceptibility, lethality and pathogenesis studies were performed. Low doses of EBOV-Kikwit, between 4 and 27 times the 50% tissue culture infectious dose, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to EVD between 6 and 8 days after challenge. Typical signs of EVD were observed. Pathogenesis studies revealed that virus was isolated from the lungs of animals beginning on day 3 after challenge and from the liver, spleen and blood beginning on day 5. The most striking features were observed in animals that succumbed to infection, including high viral titers in all organs, increased levels of liver function enzymes and blood clotting times, decreased levels of platelets, multifocal moderate to severe hepatitis, and perivascular edema. © Crown copyright 2015.

Color-Change Detection Activity in the Primate Superior Colliculus.

PubMed

Herman, James P; Krauzlis, Richard J

2017-01-01

The primate superior colliculus (SC) is a midbrain structure that participates in the control of spatial attention. Previous studies examining the role of the SC in attention have mostly used luminance-based visual features (e.g., motion, contrast) as the stimuli and saccadic eye movements as the behavioral response, both of which are known to modulate the activity of SC neurons. To explore the limits of the SC's involvement in the control of spatial attention, we recorded SC neuronal activity during a task using color, a visual feature dimension not traditionally associated with the SC, and required monkeys to detect threshold-level changes in the saturation of a cued stimulus by releasing a joystick during maintained fixation. Using this color-based spatial attention task, we found substantial cue-related modulation in all categories of visually responsive neurons in the intermediate layers of the SC. Notably, near-threshold changes in color saturation, both increases and decreases, evoked phasic bursts of activity with magnitudes as large as those evoked by stimulus onset. This change-detection activity had two distinctive features: activity for hits was larger than for misses, and the timing of change-detection activity accounted for 67% of joystick release latency, even though it preceded the release by at least 200 ms. We conclude that during attention tasks, SC activity denotes the behavioral relevance of the stimulus regardless of feature dimension and that phasic event-related SC activity is suitable to guide the selection of manual responses as well as saccadic eye movements.

Visual adaptation and novelty responses in the superior colliculus

PubMed Central

Boehnke, Susan E.; Berg, David J.; Marino, Robert M.; Baldi, Pierre F.; Itti, Laurent; Munoz, Douglas P.

2011-01-01

The brain's ability to ignore repeating, often redundant, information while enhancing novel information processing is paramount to survival. When stimuli are repeatedly presented, the response of visually-sensitive neurons decreases in magnitude, i.e. neurons adapt or habituate, although the mechanism is not yet known. We monitored activity of visual neurons in the superior colliculus (SC) of rhesus monkeys who actively fixated while repeated visual events were presented. We dissociated adaptation from habituation as mechanisms of the response decrement by using a Bayesian model of adaptation, and by employing a paradigm including rare trials that included an oddball stimulus that was either brighter or dimmer. If the mechanism is adaptation, response recovery should be seen only for the brighter stimulus; if habituation, response recovery (‘dishabituation’) should be seen for both the brighter and dimmer stimulus. We observed a reduction in the magnitude of the initial transient response and an increase in response onset latency with stimulus repetition for all visually responsive neurons in the SC. Response decrement was successfully captured by the adaptation model which also predicted the effects of presentation rate and rare luminance changes. However, in a subset of neurons with sustained activity to visual stimuli, a novelty signal akin to dishabituation was observed late in the visual response profile to both brighter and dimmer stimuli and was not captured by the model. This suggests that SC neurons integrate both rapidly discounted information about repeating stimuli and novelty information about oddball events, to support efficient selection in a cluttered dynamic world. PMID:21864319

Superior colliculus neurons encode a visual saliency map during free viewing of natural dynamic video

NASA Astrophysics Data System (ADS)

White, Brian J.; Berg, David J.; Kan, Janis Y.; Marino, Robert A.; Itti, Laurent; Munoz, Douglas P.

2017-01-01

Models of visual attention postulate the existence of a saliency map whose function is to guide attention and gaze to the most conspicuous regions in a visual scene. Although cortical representations of saliency have been reported, there is mounting evidence for a subcortical saliency mechanism, which pre-dates the evolution of neocortex. Here, we conduct a strong test of the saliency hypothesis by comparing the output of a well-established computational saliency model with the activation of neurons in the primate superior colliculus (SC), a midbrain structure associated with attention and gaze, while monkeys watched video of natural scenes. We find that the activity of SC superficial visual-layer neurons (SCs), specifically, is well-predicted by the model. This saliency representation is unlikely to be inherited from fronto-parietal cortices, which do not project to SCs, but may be computed in SCs and relayed to other areas via tectothalamic pathways.

[Anatomy of fractures of the inferior scapular angle].

PubMed

Bartoníček, J; Tuček, M; Malík, J

2018-01-01

The aim of this study is to describe the anatomy of fractures of the inferior angle and the adjacent part of the scapular body, based on 3D CT reconstructions. In a series of 375 scapular fractures, we identified a total of 20 fractures of the inferior angle of the scapular body (13 men, 7 women), with a mean patient age of 50 years (range 3373). In all fractures, 3D CT reconstructions were obtained, allowing an objective evaluation of the fracture pattern with a focus on the size and shape of the inferior angle fragment, propagation of the fracture line to the lateral and medial borders of the infraspinous part of the scapular body, fragment displacement and any additional fracture of the ipsilateral scapula and the shoulder girdle. We identified a total of 5 types of fracture involving the distal half of the infraspinous part of the scapular body. The first type, recorded in 5 cases, affected only the apex of the inferior angle, with a small part of the adjacent medial border. The second type, occurring in 4 cases, involved fractures separating the entire inferior angle. The third type, represented by 4 cases, was characterized by a fracture line starting medially close above the inferior angle and passing proximolaterally. The separated fragment had a shape of a big drop, carrying also the distal half of the lateral pillar in addition to the inferior angle. In the fourth type identified in 5 fractures, the separated fragment was formed both by the inferior angle and a variable part of the medial border. The fifth type, being by its nature a transition to the fracture of the infraspinous part of the body, was recorded in 2 cases, with the same V-shaped fragment. Fractures of the inferior angle and the adjacent part of the scapular body are groups of fractures differing from other infraspinous fractures of the scapular body. Although these fractures are highly variable in terms of shape, they have the same course of fracture line and the manner of displacement

Individual differences in choice (in)flexibility but not impulsivity in the common marmoset: an automated, operant-behavior choice task.

PubMed

Adriani, Walter; Romani, Chiara; Manciocco, Arianna; Vitale, Augusto; Laviola, Giovanni

2013-11-01

Individual differences in behavioural flexibility are a significant issue in human psychopathology as well as in its animal models. We aimed to investigate individual variations of operant-choice behaviour in the common marmoset (Callithrix jacchus), a small New World primate, using a new operant panel with two hand-poking holes. Experimental subjects (N=16) were presented with a choice between a Small & Soon (SS) vs a Large & Late (LL) food reward. After extensive training (31 daily sessions with no delay, during which a basal, large-reward preference developed), the delay before release of LL was progressively increased (from 0 to 60 s, during 16 daily sessions; indifferent point at delay=9 s). Subjects were classified as either "flexible" or "non-flexible", respectively, based on a decrease (or not) in the preference for LL with increasing delays. Each subject was also classified as "maximizer" (or "non-maximizer") based on capacity (or not) to maximize the food payoff as delay increased. Upon delays shorter than the indifferent point (<9s), none of the subjects showed a shift from LL to SS, denoting a lack of delay-induced, cognitive impulsivity. Individual differences only emerged upon delays longer than the indifferent point (>9 s), when a preference shift could be interpreted as economically-driven. In general, a profile of few unrewarded hand-pokes in reaction to initial delays (i.e., a low motor impulsivity) and of clear-cut basal LL preference seemed to predict elevated flexibility of choices and better food payoff, which was typical of subjects classified as both "flexible & maximizer". These results provide normative data on the marmosets, which can be used as a model for the investigation of 1) individual differences in behavioural flexibility, as well as 2) biological mechanisms rooted in our evolutionary history. Copyright © 2013 Elsevier B.V. All rights reserved.

Translocation and radio-telemetry monitoring of pygmy marmoset, Cebuella pygmaea (Spix, 1823), in the Brazilian Amazon.

PubMed

Dias, C A R; Queirogas, V L; Pedersoli, M A

2015-01-01

Two groups of pygmy marmoset (Cebuella pygmaea) were rescued along the left bank of the Madeira River during the formation of Santo Antônio Hydroelectric Dam reservoir in the state of Rondônia, Northern Brazil. Reintroduction of both groups occurred in areas of open Tropical rainforest located within the project´s Permanent Preservation Area. A post-release monitoring was conducted for three months using radio-telemetry. Individuals of each group remained together and settled in stable home ranges near their respective release sites. The mortality rate of translocated animals was about 7%. This seems to be the first report documenting the complete group translocation of C. pygmaea and the first to successfully employ radio-telemetry techniques in monitoring this species. This study demonstrated the feasibility of translocation and the use of radio-telemetry in monitoring C. pygmaea.

Prehospital Nitroglycerin Safety in Inferior ST Elevation Myocardial Infarction.

PubMed

Robichaud, Laurie; Ross, Dave; Proulx, Marie-Hélène; Légaré, Sébastien; Vacon, Charlene; Xue, Xiaoqing; Segal, Eli

2016-01-01

Patients with inferior ST elevation myocardial infarction (STEMI), associated with right ventricular infarction, are thought to be at higher risk of developing hypotension when administered nitroglycerin (NTG). However, current basic life support (BLS) protocols do not differentiate location of STEMI prior to NTG administration. We sought to determine if NTG administration is more likely to be associated with hypotension (systolic blood pressure < 90 mmHg) in inferior STEMI compared to non-inferior STEMI. We conducted a retrospective chart review of prehospital patients with chest pain of suspected cardiac origin and computer-interpreted prehospital ECGs indicating "ACUTE MI." We included all local STEMI cases identified as part of our STEMI registry. Univariate analysis was used to compare differences in proportions of hypotension and drop in systolic blood pressure ≥ 30 mmHg after nitroglycerin administration between patients with inferior wall STEMI and those with STEMI in another region (non-inferior). Multiple variable logistic regression analysis was also used to assess the study outcomes while controlling for various factors. Over a 29-month period, we identified 1,466 STEMI cases. Of those, 821 (56.0%) received NTG. We excluded 16 cases because of missing data. Hypotension occurred post NTG in 38/466 inferior STEMIs and 30/339 non-inferior STEMIs, 8.2% vs. 8.9%, p = 0.73. A drop in systolic blood pressure ≥ 30 mmHg post NTG occurred in 23.4% of inferior STEMIs and 23.9% of non-inferior STEMIs, p = 0.87. Interrater agreement for chart review of the primary outcome was excellent (κ = 0.94). NTG administration to patients with chest pain and inferior STEMI on their computer-interpreted electrocardiogram is not associated with a higher rate of hypotension compared to patients with STEMI in other territories. Computer interpretation of inferior STEMI cannot be used as the sole predictor for patients who may be at higher risk for hypotension following NTG

Added clinical value of the inferior temporal EEG electrode chain.

PubMed

Bach Justesen, Anders; Eskelund Johansen, Ann Berit; Martinussen, Noomi Ida; Wasserman, Danielle; Terney, Daniella; Meritam, Pirgit; Gardella, Elena; Beniczky, Sándor

2018-01-01

To investigate the diagnostic added value of supplementing the 10-20 EEG array with six electrodes in the inferior temporal chain. EEGs were recorded with 25 electrodes: 19 positions of the 10-20 system, and six additional electrodes in the inferior temporal chain (F9/10, T9/10, P9/10). Five-hundred consecutive standard and sleep EEG recordings were reviewed using the 10-20 array and the extended array. We identified the recordings with EEG abnormalities that had peak negativities at the inferior temporal electrodes, and those that only were visible at the inferior temporal electrodes. From the 286 abnormal recordings, the peak negativity was at the inferior temporal electrodes in 81 cases (28.3%) and only visible at the inferior temporal electrodes in eight cases (2.8%). In the sub-group of patients with temporal abnormalities (n = 134), these represented 59% (peak in the inferior chain) and 6% (only seen at the inferior chain). Adding six electrodes in the inferior temporal electrode chain to the 10-20 array improves the localization and identification of EEG abnormalities, especially those located in the temporal region. Our results suggest that inferior temporal electrodes should be added to the EEG array, to increase the diagnostic yield of the recordings. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Resonant Cholinergic Dynamics in Cognitive and Motor Decision-Making: Attention, Category Learning, and Choice in Neocortex, Superior Colliculus, and Optic Tectum.

PubMed

Grossberg, Stephen; Palma, Jesse; Versace, Massimiliano

2015-01-01

Freely behaving organisms need to rapidly calibrate their perceptual, cognitive, and motor decisions based on continuously changing environmental conditions. These plastic changes include sharpening or broadening of cognitive and motor attention and learning to match the behavioral demands that are imposed by changing environmental statistics. This article proposes that a shared circuit design for such flexible decision-making is used in specific cognitive and motor circuits, and that both types of circuits use acetylcholine to modulate choice selectivity. Such task-sensitive control is proposed to control thalamocortical choice of the critical features that are cognitively attended and that are incorporated through learning into prototypes of visual recognition categories. A cholinergically-modulated process of vigilance control determines if a recognition category and its attended features are abstract (low vigilance) or concrete (high vigilance). Homologous neural mechanisms of cholinergic modulation are proposed to focus attention and learn a multimodal map within the deeper layers of superior colliculus. This map enables visual, auditory, and planned movement commands to compete for attention, leading to selection of a winning position that controls where the next saccadic eye movement will go. Such map learning may be viewed as a kind of attentive motor category learning. The article hereby explicates a link between attention, learning, and cholinergic modulation during decision making within both cognitive and motor systems. Homologs between the mammalian superior colliculus and the avian optic tectum lead to predictions about how multimodal map learning may occur in the mammalian and avian brain and how such learning may be modulated by acetycholine.

Resonant Cholinergic Dynamics in Cognitive and Motor Decision-Making: Attention, Category Learning, and Choice in Neocortex, Superior Colliculus, and Optic Tectum

PubMed Central

Grossberg, Stephen; Palma, Jesse; Versace, Massimiliano

2016-01-01

Freely behaving organisms need to rapidly calibrate their perceptual, cognitive, and motor decisions based on continuously changing environmental conditions. These plastic changes include sharpening or broadening of cognitive and motor attention and learning to match the behavioral demands that are imposed by changing environmental statistics. This article proposes that a shared circuit design for such flexible decision-making is used in specific cognitive and motor circuits, and that both types of circuits use acetylcholine to modulate choice selectivity. Such task-sensitive control is proposed to control thalamocortical choice of the critical features that are cognitively attended and that are incorporated through learning into prototypes of visual recognition categories. A cholinergically-modulated process of vigilance control determines if a recognition category and its attended features are abstract (low vigilance) or concrete (high vigilance). Homologous neural mechanisms of cholinergic modulation are proposed to focus attention and learn a multimodal map within the deeper layers of superior colliculus. This map enables visual, auditory, and planned movement commands to compete for attention, leading to selection of a winning position that controls where the next saccadic eye movement will go. Such map learning may be viewed as a kind of attentive motor category learning. The article hereby explicates a link between attention, learning, and cholinergic modulation during decision making within both cognitive and motor systems. Homologs between the mammalian superior colliculus and the avian optic tectum lead to predictions about how multimodal map learning may occur in the mammalian and avian brain and how such learning may be modulated by acetycholine. PMID:26834535

Functional Mapping of the Human Auditory Cortex: fMRI Investigation of a Patient with Auditory Agnosia from Trauma to the Inferior Colliculus.

PubMed

Poliva, Oren; Bestelmeyer, Patricia E G; Hall, Michelle; Bultitude, Janet H; Koller, Kristin; Rafal, Robert D

2015-09-01

To use functional magnetic resonance imaging to map the auditory cortical fields that are activated, or nonreactive, to sounds in patient M.L., who has auditory agnosia caused by trauma to the inferior colliculi. The patient cannot recognize speech or environmental sounds. Her discrimination is greatly facilitated by context and visibility of the speaker's facial movements, and under forced-choice testing. Her auditory temporal resolution is severely compromised. Her discrimination is more impaired for words differing in voice onset time than place of articulation. Words presented to her right ear are extinguished with dichotic presentation; auditory stimuli in the right hemifield are mislocalized to the left. We used functional magnetic resonance imaging to examine cortical activations to different categories of meaningful sounds embedded in a block design. Sounds activated the caudal sub-area of M.L.'s primary auditory cortex (hA1) bilaterally and her right posterior superior temporal gyrus (auditory dorsal stream), but not the rostral sub-area (hR) of her primary auditory cortex or the anterior superior temporal gyrus in either hemisphere (auditory ventral stream). Auditory agnosia reflects dysfunction of the auditory ventral stream. The ventral and dorsal auditory streams are already segregated as early as the primary auditory cortex, with the ventral stream projecting from hR and the dorsal stream from hA1. M.L.'s leftward localization bias, preserved audiovisual integration, and phoneme perception are explained by preserved processing in her right auditory dorsal stream.

A Case of Blunt Trauma of the Eyeball Associated With an Inferior Oblique Muscle and an Inferior Rectus Muscle Rupture.

PubMed

Nitta, Keisuke; Kashima, Tomoyuki; Miura, Fumihide; Hiroe, Takashi; Akiyama, Hideo; Kishi, Shoji

2016-01-01

Rupture of the extraocular muscle in the absence of significant injury to the eyeball and adnexa is uncommon. The authors report a case of blunt trauma of the eyeball associated with an inferior oblique muscle and an inferior rectus muscle rupture. A 55-year-old man slipped and fell down hitting his eye on an extended windshield wiper blade. Although he had treatment in the emergency room, he complained of diplopia in the primary position 1 day postoperatively. After noticing ruptures of the inferior oblique muscle and an inferior rectus muscle during exploratory surgery, the authors carefully repaired it. Diplopia in the primary position had disappeared within 1 month after the operation and by 6 months postoperatively. The movement of the eye had almost completely recovered.

Can vocal conditioning trigger a semiotic ratchet in marmosets?

PubMed

Turesson, Hjalmar K; Ribeiro, Sidarta

2015-01-01

The complexity of human communication has often been taken as evidence that our language reflects a true evolutionary leap, bearing little resemblance to any other animal communication system. The putative uniqueness of the human language poses serious evolutionary and ethological challenges to a rational explanation of human communication. Here we review ethological, anatomical, molecular, and computational results across several species to set boundaries for these challenges. Results from animal behavior, cognitive psychology, neurobiology, and semiotics indicate that human language shares multiple features with other primate communication systems, such as specialized brain circuits for sensorimotor processing, the capability for indexical (pointing) and symbolic (referential) signaling, the importance of shared intentionality for associative learning, affective conditioning and parental scaffolding of vocal production. The most substantial differences lie in the higher human capacity for symbolic compositionality, fast vertical transmission of new symbols across generations, and irreversible accumulation of novel adaptive behaviors (cultural ratchet). We hypothesize that increasingly-complex vocal conditioning of an appropriate animal model may be sufficient to trigger a semiotic ratchet, evidenced by progressive sign complexification, as spontaneous contact calls become indexes, then symbols and finally arguments (strings of symbols). To test this hypothesis, we outline a series of conditioning experiments in the common marmoset (Callithrix jacchus). The experiments are designed to probe the limits of vocal communication in a prosocial, highly vocal primate 35 million years far from the human lineage, so as to shed light on the mechanisms of semiotic complexification and cultural transmission, and serve as a naturalistic behavioral setting for the investigation of language disorders.

Can vocal conditioning trigger a semiotic ratchet in marmosets?

PubMed Central

Turesson, Hjalmar K.; Ribeiro, Sidarta

2015-01-01

The complexity of human communication has often been taken as evidence that our language reflects a true evolutionary leap, bearing little resemblance to any other animal communication system. The putative uniqueness of the human language poses serious evolutionary and ethological challenges to a rational explanation of human communication. Here we review ethological, anatomical, molecular, and computational results across several species to set boundaries for these challenges. Results from animal behavior, cognitive psychology, neurobiology, and semiotics indicate that human language shares multiple features with other primate communication systems, such as specialized brain circuits for sensorimotor processing, the capability for indexical (pointing) and symbolic (referential) signaling, the importance of shared intentionality for associative learning, affective conditioning and parental scaffolding of vocal production. The most substantial differences lie in the higher human capacity for symbolic compositionality, fast vertical transmission of new symbols across generations, and irreversible accumulation of novel adaptive behaviors (cultural ratchet). We hypothesize that increasingly-complex vocal conditioning of an appropriate animal model may be sufficient to trigger a semiotic ratchet, evidenced by progressive sign complexification, as spontaneous contact calls become indexes, then symbols and finally arguments (strings of symbols). To test this hypothesis, we outline a series of conditioning experiments in the common marmoset (Callithrix jacchus). The experiments are designed to probe the limits of vocal communication in a prosocial, highly vocal primate 35 million years far from the human lineage, so as to shed light on the mechanisms of semiotic complexification and cultural transmission, and serve as a naturalistic behavioral setting for the investigation of language disorders. PMID:26500583

Inferiority is compex

NASA Astrophysics Data System (ADS)

Wade, Jess

2017-07-01

In Inferior: How Science Got Women Wrong and the New Research That's Rewriting the Story, author Angela Saini puts forward the idea that bad science has been used to endorse the cultural prejudice that women are both biologically and psychologically second rate to men.

A Layer-specific Corticofugal Input to the Mouse Superior Colliculus.

PubMed

Zurita, Hector; Rock, Crystal; Perkins, Jessica; Apicella, Alfonso Junior

2017-07-05

In the auditory cortex (AC), corticofugal projections arise from each level of the auditory system and are considered to provide feedback "loops" important to modulate the flow of ascending information. It is well established that the cortex can influence the response of neurons in the superior colliculus (SC) via descending corticofugal projections. However, little is known about the relative contribution of different pyramidal neurons to these projections in the SC. We addressed this question by taking advantage of anterograde and retrograde neuronal tracing to directly examine the laminar distribution, long-range projections, and electrophysiological properties of pyramidal neurons projecting from the AC to the SC of the mouse brain. Here we show that layer 5 cortico-superior-collicular pyramidal neurons act as bandpass filters, resonating with a broad peak at ∼3 Hz, whereas layer 6 neurons act as low-pass filters. The dissimilar subthreshold properties of layer 5 and layer 6 cortico-superior-collicular pyramidal neurons can be described by differences in the hyperpolarization-activated cyclic nucleotide-gated cation h-current (Ih). Ih also reduced the summation of short trains of artificial excitatory postsynaptic potentials injected at the soma of layer 5, but not layer 6, cortico-superior-collicular pyramidal neurons, indicating a differential dampening effect of Ih on these neurons. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Relationship between body temperature, weight, and hematological parameters of black tufted-ear marmosets (Callithrix penicillata).

PubMed

Pereira, Lucas Cardoso; Barros, Marilia

2016-06-01

Basal thermal values of captive adult black tufted-ear marmosets (Callithrix penicillata) in a thermoneutral environment were measured via different methods, along with body weight and hematological parameters. Body temperatures were recorded with rectal (RC), subcutaneous (SC) microchip transponder and infrared (left and right) tympanic membrane (TM) thermometries. Thermal values were correlated with body mass and some hematological data. Similar RC and SC temperatures were observed, these being significantly higher than the left and right TM values. SC temperature was positively correlated and in close agreement with RC measurements. Although body temperatures were not influenced by gender, capture time, or body weight, they were correlated with hematological parameters. Thus, body temperatures in this species seem to reflect some of the characteristics of the assessments' location, with SC microchip transponders being a less invasive method to assess body temperature in these small-bodied non-human primates. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inferior vena caval masses identified by echocardiography

NASA Technical Reports Server (NTRS)

Sun, J. P.; Asher, C. R.; Xu, Y.; Huang, V.; Griffin, B. P.; Stewart, W. J.; Novick, A. C.; Thomas, J. D.

1999-01-01

The most common cause of an inferior vena caval mass is renal cell carcinoma that extends through the lumen, occurring in 47 of 62 patients (85%). Detection of an inferior vena caval mass affects the surgical approach requiring cardiopulmonary bypass for resection when the mass extends to the heart.

Inflammatory fibroid polyp in the duodenum of a common marmoset (Callithrix jacchus).

PubMed

Yokouchi, Yusuke; Imaoka, Masako; Sayama, Ayako; Jindo, Toshimasa; Sanbuissho, Atsushi

2013-01-01

A 32-month-old male common marmoset had a firm and white-colored mass in the duodenal wall. The cut surface was smooth and grayish white in color. Histologically, the mass consisted of a proliferation of spindle cells with an oval to spindle-shaped nucleus and scant eosinophilic cytoplasm in a loose myxoid or fibrotic background. Most of the lesion displayed no specific growth pattern whereas some of the cells concentrated around the vessels and created an onion-bulb structure. Additionally, marked inflammatory cellular infiltration, mainly eosinophils, was observed throughout the lesion. Immunohistochemically, the spindle cells were positive for vimentin, α-smooth muscle actin, fascin, and cyclin D1, and negative for S-100, factor VIII-related antigen, and c-kit. These histological and immunohistochemical features did not meet any differential diagnoses such as gastrointestinal stromal tumor, inflammatory myofibroblastic tumor, solitary fibrous tumor/hemangiopericytoma, smooth muscle tumor, schwannoma, and hemangiosarcoma. Collectively, the authors diagnosed the mass as a lesion that corresponded to an inflammatory fibroid polyp (IFP) in humans. IFP is defined as a mesenchymal proliferation composed of spindle stromal cells, small blood vessels, and inflammatory cells, particularly eosinophils, and is currently classified as a nonneoplastic lesion. To the best of our knowledge, this is the first case of spontaneous IFP in nonhuman primates.

[Inferior vestibular neuritis: diagnosis using VEMP].

PubMed

Walther, L E; Repik, I

2012-02-01

Vestibular evoked myogenic potentials (VEMP) are a new method to establish the functional status of the otolith organs. The sacculocollic reflex of the cervical VEMP to air conduction (AC) reflects predominantly saccular function due to saccular afferents to the inferior vestibular nerve. We describe a case of inferior vestibular neuritis as a rare differential diagnosis of vestibular neuritis. Clinical signs were a normal caloric response, unilaterally absent AC cVEMPs and bilaterally preserved ocular VEMPs (AC oVEMPs).

Segregation of Visual Response Properties in the Mouse Superior Colliculus and Their Modulation during Locomotion

PubMed Central

2017-01-01

The superior colliculus (SC) receives direct input from the retina and integrates it with information about sound, touch, and state of the animal that is relayed from other parts of the brain to initiate specific behavioral outcomes. The superficial SC layers (sSC) contain cells that respond to visual stimuli, whereas the deep SC layers (dSC) contain cells that also respond to auditory and somatosensory stimuli. Here, we used a large-scale silicon probe recording system to examine the visual response properties of SC cells of head-fixed and alert male mice. We found cells with diverse response properties including: (1) orientation/direction-selective (OS/DS) cells with a firing rate that is suppressed by drifting sinusoidal gratings (negative OS/DS cells); (2) suppressed-by-contrast cells; (3) cells with complex-like spatial summation nonlinearity; and (4) cells with Y-like spatial summation nonlinearity. We also found specific response properties that are enriched in different depths of the SC. The sSC is enriched with cells with small RFs, high evoked firing rates (FRs), and sustained temporal responses, whereas the dSC is enriched with the negative OS/DS cells and with cells with large RFs, low evoked FRs, and transient temporal responses. Locomotion modulates the activity of the SC cells both additively and multiplicatively and changes the preferred spatial frequency of some SC cells. These results provide the first description of the negative OS/DS cells and demonstrate that the SC segregates cells with different response properties and that the behavioral state of a mouse affects SC activity. SIGNIFICANCE STATEMENT The superior colliculus (SC) receives visual input from the retina in its superficial layers (sSC) and induces eye/head-orientating movements and innate defensive responses in its deeper layers (dSC). Despite their importance, very little is known about the visual response properties of dSC neurons. Using high-density electrode recordings and novel

A Model of the Superior Colliculus Predicts Fixation Locations during Scene Viewing and Visual Search.

PubMed

Adeli, Hossein; Vitu, Françoise; Zelinsky, Gregory J

2017-02-08

Modern computational models of attention predict fixations using saliency maps and target maps, which prioritize locations for fixation based on feature contrast and target goals, respectively. But whereas many such models are biologically plausible, none have looked to the oculomotor system for design constraints or parameter specification. Conversely, although most models of saccade programming are tightly coupled to underlying neurophysiology, none have been tested using real-world stimuli and tasks. We combined the strengths of these two approaches in MASC, a model of attention in the superior colliculus (SC) that captures known neurophysiological constraints on saccade programming. We show that MASC predicted the fixation locations of humans freely viewing naturalistic scenes and performing exemplar and categorical search tasks, a breadth achieved by no other existing model. Moreover, it did this as well or better than its more specialized state-of-the-art competitors. MASC's predictive success stems from its inclusion of high-level but core principles of SC organization: an over-representation of foveal information, size-invariant population codes, cascaded population averaging over distorted visual and motor maps, and competition between motor point images for saccade programming, all of which cause further modulation of priority (attention) after projection of saliency and target maps to the SC. Only by incorporating these organizing brain principles into our models can we fully understand the transformation of complex visual information into the saccade programs underlying movements of overt attention. With MASC, a theoretical footing now exists to generate and test computationally explicit predictions of behavioral and neural responses in visually complex real-world contexts. SIGNIFICANCE STATEMENT The superior colliculus (SC) performs a visual-to-motor transformation vital to overt attention, but existing SC models cannot predict saccades to visually

Level-tolerant duration selectivity in the auditory cortex of the velvety free-tailed bat Molossus molossus.

PubMed

Macías, Silvio; Hernández-Abad, Annette; Hechavarría, Julio C; Kössl, Manfred; Mora, Emanuel C

2015-05-01

It has been reported previously that in the inferior colliculus of the bat Molossus molossus, neuronal duration tuning is ambiguous because the tuning type of the neurons dramatically changes with the sound level. In the present study, duration tuning was examined in the auditory cortex of M. molossus to describe if it is as ambiguous as the collicular tuning. From a population of 174 cortical 104 (60 %) neurons did not show duration selectivity (all-pass). Around 5 % (9 units) responded preferentially to stimuli having longer durations showing long-pass duration response functions, 35 (20 %) responded to a narrow range of stimulus durations showing band-pass duration response functions, 24 (14 %) responded most strongly to short stimulus durations showing short-pass duration response functions and two neurons (1 %) responded best to two different stimulus durations showing a two-peaked duration-response function. The majority of neurons showing short- (16 out of 24) and band-pass (24 out 35) selectivity displayed "O-shaped" duration response areas. In contrast to the inferior colliculus, duration tuning in the auditory cortex of M. molossus appears level tolerant. That is, the type of duration selectivity and the stimulus duration eliciting the maximum response were unaffected by changing sound level.

Lateralization Technique and Inferior Alveolar Nerve Transposition

PubMed Central

Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

2016-01-01

Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

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

Methods in Computational Neuroscience Course: Student Project Descriptions

DTIC Science & Technology

1989-09-02

form of a "peri Geniculate Nucleus"). Currently, for some yet unknown reason (probably the lateral inhibition) layer 6 shows symmetrical end-inhibition...40 neurons each) in the inferior colliculus served as inputs to a sheet of 100 cells within the medial geniculate body where combination sensitivity is...tertiary dendritic function in the bushy cells, as well as lateral inhibition in the AVCN stellate cells yielded the results that feedback inhibition

Complications following total inferior turbinectomy: facts or myths?

PubMed

Odetoyinbo, O

1987-10-01

Various surgical procedures have been described for the relief of chronic nasal obstruction due to inferior turbinate hypertrophy, but none has been consistently satisfactory. We have performed total inferior turbinectomy for this condition for 5 years. Of the 39 patients followed for at least 2 years, 90% were relieved permanently of nasal obstruction. However, only 36% and 61% of patients with rhinorrhoea and anosmia respectively were relieved of these symptoms. Complications were minimal. It is concluded that even in a dry, dusty tropical climate, inferior turbinectomy does not appear to disturb the function of the nasal cavity appreciably.

Inferior sinus venosus defect: echocardiographic diagnosis and surgical approach.

PubMed

Crystal, Matthew A; Al Najashi, Khaled; Williams, William G; Redington, Andrew N; Anderson, Robert H

2009-06-01

We sought to define the inferior sinus venosus defect anatomically and document successful surgical approaches. We identified all patients previously given a diagnosis of an inferior sinus venosus defect at the Hospital for Sick Children, Toronto, Canada, between 1982 and 2005 by interrogating the cardiology and cardiac surgery databases. We included those having interatrial communications in which 1 or more of the right pulmonary veins drained to the inferior caval vein but retained connection with the left atrium, the rims of the oval fossa, and the walls of the coronary sinus, both being intact. We identified 11 children who had an interatrial communication meeting the criteria for and undergoing surgical repair of an inferior sinus venosus defect. Median age was 1.2 years; 6 (55%) subjects were male, and none were cyanotic. Transthoracic echocardiographic analysis was performed preoperatively in all children, revealing right ventricular dilation in all. Surgical repair was accomplished with a pericardial patch. A complex baffle was needed in 3 children to maintain unobstructed inferior caval and pulmonary venous return. The echocardiographic diagnosis was complete in only 5 patients, but all diagnoses were correct since the year 2000. In all children the observations at surgical intervention showed that the defect was a venoatrial communication involving drainage of the right pulmonary veins to the inferior caval vein while retaining connection to the left atrium. Transthoracic echocardiographic analysis should remain the modality of choice for diagnosis of the inferior sinus venosus defect. We report excellent surgical results with a patch or baffle, correctly redirecting the anomalous venoatrial connections.

Enhancing effects of nicotine and impairing effects of scopolamine on distinct aspects of performance in computerized attention and working memory tasks in marmoset monkeys.

PubMed

Spinelli, Simona; Ballard, Theresa; Feldon, Joram; Higgins, Guy A; Pryce, Christopher R

2006-08-01

With the CAmbridge Neuropsychological Test Automated Battery (CANTAB), computerized neuropsychological tasks can be presented on a touch-sensitive computer screen, and this system has been used to assess cognitive processes in neuropsychiatric patients, healthy volunteers, and species of non-human primate, primarily the rhesus macaque and common marmoset. Recently, we reported that the common marmoset, a small-bodied primate, can be trained to a high and stable level of performance on the CANTAB five-choice serial reaction time (5-CSRT) task of attention, and a novel task of working memory, the concurrent delayed match-to-position (CDMP) task. Here, in order to increase understanding of the specific cognitive demands of these tasks and the importance of acetylcholine to their performance, the effects of systemic delivery of the muscarinic receptor antagonist scopolamine and the nicotinic receptor agonist nicotine were studied. In the 5-CSRT task, nicotine enhanced performance in terms of increased sustained attention, whilst scopolamine led to increased omissions despite a high level of orientation to the correct stimulus location. In the CDMP task, scopolamine impaired performance at two stages of the task that differ moderately in terms of memory retention load but both of which are likely to require working memory, including interference-coping, abilities. Nicotine tended to enhance performance at the long-delay stage specifically but only against a background of relatively low baseline performance. These data are consistent with a dissociation of the roles of muscarinic and nicotinic cholinergic receptors in the regulation of both sustained attention and working memory in primates.

Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset

PubMed Central

Jackson, Stacey A. W.; Horst, Nicole K.; Pears, Andrew; Robbins, Trevor W.; Roberts, Angela C.

2016-01-01

Two learning mechanisms contribute to decision-making: goal-directed actions and the “habit” system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior. PMID:27130662

Non-recurrent inferior laryngeal nerve identification during robotic thyroidectomy.

PubMed

Wang, C-C; Wu, C-H

2014-02-01

A non-recurrent inferior laryngeal nerve is a rare anomaly in which the nerve enters the larynx directly off the cervical vagus nerve, without descending to the thoracic level. It is very susceptible to damage during surgery. This report describes the important pre-operative radiological evaluations and surgical landmarks in a case of a non-recurrent inferior laryngeal nerve, identified during the recently developed technique of robotic thyroidectomy. A 38-year-old woman presented with suspected papillary microcarcinoma, as indicated by aspiration cytology. Pre-operative computed tomography showed a right aberrant subclavian artery that indicated a possible right non-recurrent inferior laryngeal nerve. Using robotic thyroidectomy methods, it was possible to carefully dissect along the thyroid capsule. The laryngeal entrance point of the right non-recurrent inferior laryngeal nerve (a constant anatomical landmark) was successfully identified via the three-dimensional, high-magnification views provided by the robotic endoscope. With proper knowledge of radiological and surgical anatomy, and the benefits of high-magnification endoscopic views, a non-recurrent inferior laryngeal nerve can be safely preserved during robotic surgery.

Variability of visual responses of superior colliculus neurons depends on stimulus velocity.

PubMed

Mochol, Gabriela; Wójcik, Daniel K; Wypych, Marek; Wróbel, Andrzej; Waleszczyk, Wioletta J

2010-03-03

Visually responding neurons in the superficial, retinorecipient layers of the cat superior colliculus receive input from two primarily parallel information processing channels, Y and W, which is reflected in their velocity response profiles. We quantified the time-dependent variability of responses of these neurons to stimuli moving with different velocities by Fano factor (FF) calculated in discrete time windows. The FF for cells responding to low-velocity stimuli, thus receiving W inputs, increased with the increase in the firing rate. In contrast, the dynamics of activity of the cells responding to fast moving stimuli, processed by Y pathway, correlated negatively with FF whether the response was excitatory or suppressive. These observations were tested against several types of surrogate data. Whereas Poisson description failed to reproduce the variability of all collicular responses, the inclusion of secondary structure to the generating point process recovered most of the observed features of responses to fast moving stimuli. Neither model could reproduce the variability of low-velocity responses, which suggests that, in this case, more complex time dependencies need to be taken into account. Our results indicate that Y and W channels may differ in reliability of responses to visual stimulation. Apart from previously reported morphological and physiological differences of the cells belonging to Y and W channels, this is a new feature distinguishing these two pathways.

Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

PubMed Central

Wang, Hom-Lay; Sabalys, Gintautas

2011-01-01

ABSTRACT Objectives The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement. Material and Methods Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies. Results In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement. Conclusions The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management. PMID:24421983

Inferior Oblique Overaction: Anterior Transposition Versus Myectomy.

PubMed

Rajavi, Zhale; Feizi, Mohadeseh; Behradfar, Narges; Yaseri, Mehdi; Sayanjali, Shima; Motevaseli, Tahmine; Sabbaghi, Hamideh; Faghihi, Mohammad

2017-07-01

To compare the efficacy of inferior oblique myectomy and anterior transposition for correcting inferior oblique overaction (IOOA). This retrospective study was conducted on 56 patients with IOOA who had either myectomy or anterior transposition of the inferior oblique muscle from 2010 to 2015. The authors compared preoperative and postoperative inferior oblique muscle function grading (-4 to +4) as the main outcome measure and vertical and horizontal deviation, dissociated vertical deviation (DVD), and A- and V-pattern between the two surgical groups as secondary outcomes. A total of 99 eyes of 56 patients with a mean age of 5.9 ± 6.5 years were included (47 eyes in the myectomy group and 52 eyes in the anterior transposition group). There were no differences in preoperative best corrected visual acuity, amblyopia, spherical equivalent, and primary versus secondary IOOA between the two groups. Both surgical procedures were effective in reducing IOOA and satisfactory results were similar between the two groups: 61.7% and 67.3% in the myectomy and anterior transposition groups, respectively (P = .56). After adjustment for the preoperative DVD, there was no statistically significant difference between the two groups postoperatively. The preoperative hypertropia was 6 to 14 and 6 to 18 prism diopters (PD) in the myectomy and anterior transposition groups, respectively. After surgery, no patient had a vertical deviation greater than 5 PD. Both the inferior oblique myectomy and anterior transposition procedures are effective in reducing IOOA with similar satisfactory results. DVD and hypertropia were also corrected similarly by these two surgical procedures. [J Pediatr Ophthalmol Strabismus. 2017;54(4):232-237.]. Copyright 2017, SLACK Incorporated.

Immunocytochemical localization of calretinin in the superficial layers of the cat superior colliculus.

PubMed

Hong, Soo-Kyung; Kim, Jee-Young; Jeon, Chang-Jin

2002-11-01

We localized calretinin-immunoreactive (IR) fibers and cells in the superior colliculus (SC) of the cat and studied the distribution and effect of enucleation on the distribution of this protein. Calretinin was localized with antibody immunocytochemistry. A dense plexus of anti-calretinin-IR fibers was found within the upper part of the superficial gray layer. Almost all of the labeled fibers were small diameter fibers with few varicosities. Monocular enucleation produced an almost complete reduction of calretinin-IR fibers in the SC contralateral to the enucleation. Furthermore, many calretinin-IR cells appeared in the contralateral SC. The newly appeared cells had small- to medium-sized vertical fusiform, oval or round, or stellate cell bodies. Two-color immunofluorescence revealed that no cells in the superficial layers expressed both calretinin and GABA. Many retinal ganglion cells were labeled after injections of retrograde axonal transport horseradish peroxidase (HRP) in the superficial layers. However, no large cells were double-labeled with calretinin and HRP. More than 95% of the double-labeled cells were small cells (<15 microm). Based on the retinal ganglion cell size, we believe that the vast majority of calretinin-IR retinocollicular fibers in cat SC are small gamma type cells that have W type physiologies.

In vivo quantification of T2* anisotropy in white matter fibers in marmoset monkeys

PubMed Central

Sati, P.; Silva, A. C.; van Gelderen, P.; Gaitan, M. I.; Wohler, J. E.; Jacobson, S.; Duyn, J. H.; Reich, D. S.

2011-01-01

T2*-weighted MRI at high field is a promising approach for studying noninvasively the tissue structure and composition of the brain. However, the biophysical origin of T2* contrast, especially in white matter, remains poorly understood. Recent work has shown that R2* (=1/T2*) may depend on the tissue’s orientation relative to the static magnetic field (B0) and suggested that this dependence could be attributed to local anisotropy in the magnetic properties of brain tissue. In the present work, we analyzed high-resolution, multi-gradient-echo images of in vivo marmoset brains at 7T, and compared them with ex vivo diffusion tensor images, to show that R2* relaxation in white matter is highly sensitive to the fiber orientation relative to the main field. We directly demonstrate this orientation dependence by performing in vivo multi-gradient-echo acquisitions in two orthogonal brain positions, uncovering a nearly 50% change in the R2*relaxation rate constant of the optic radiations. We attribute this substantial R2* anisotropy to local subvoxel susceptibility effects arising from the highly ordered and anisotropic structure of the myelin sheath. PMID:21906687

Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus)

PubMed Central

Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

2013-01-01

Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals’ lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. PMID:23441639

Intraosseous Hemangioma of the Inferior Turbinate

PubMed Central

Takeda, Kazuya; Takenaka, Yukinori; Hashimoto, Michiko

2010-01-01

The nasal cavity harbors an enormous variety of neoplasms, including epithelial and mesenchymal tumors. Hemangioma is an infrequent mesenchymal tumor of the nasal cavity, mostly arising in the mucosa and rarely in the bones. We describe the case of a 73-year-old woman who was referred to our hospital with a tumor in her left nasal cavity. The tumor originated from the left inferior turbinate. Histological examination subsequent to complete excision revealed that the tumor was an intraosseous cavernous hemangioma. To our knowledge, this is the second case of intraosseous hemangioma of the inferior turbinate reported in the English literature. PMID:20300428

Does the Superior Colliculus Control Perceptual Sensitivity or Choice Bias during Attention? Evidence from a Multialternative Decision Framework

PubMed Central

Steinmetz, Nicholas A.; Moore, Tirin; Knudsen, Eric I.

2017-01-01

Distinct networks in the forebrain and the midbrain coordinate to control spatial attention. The critical involvement of the superior colliculus (SC)—the central structure in the midbrain network—in visuospatial attention has been shown by four seminal, published studies in monkeys (Macaca mulatta) performing multialternative tasks. However, due to the lack of a mechanistic framework for interpreting behavioral data in such tasks, the nature of the SC's contribution to attention remains unclear. Here we present and validate a novel decision framework for analyzing behavioral data in multialternative attention tasks. We apply this framework to re-examine the behavioral evidence from these published studies. Our model is a multidimensional extension to signal detection theory that distinguishes between two major classes of attentional mechanisms: those that alter the quality of sensory information or “sensitivity,” and those that alter the selective gating of sensory information or “choice bias.” Model-based simulations and model-based analyses of data from these published studies revealed a converging pattern of results that indicated that choice-bias changes, rather than sensitivity changes, were the primary outcome of SC manipulation. Our results suggest that the SC contributes to attentional performance predominantly by generating a spatial choice bias for stimuli at a selected location, and that this bias operates downstream of forebrain mechanisms that enhance sensitivity. The findings lead to a testable mechanistic framework of how the midbrain and forebrain networks interact to control spatial attention. SIGNIFICANCE STATEMENT Attention involves the selection of the most relevant information for differential sensory processing and decision making. While the mechanisms by which attention alters sensory encoding (sensitivity control) are well studied, the mechanisms by which attention alters decisional weighting of sensory evidence (choice

Does the Superior Colliculus Control Perceptual Sensitivity or Choice Bias during Attention? Evidence from a Multialternative Decision Framework.

PubMed

Sridharan, Devarajan; Steinmetz, Nicholas A; Moore, Tirin; Knudsen, Eric I

2017-01-18

Distinct networks in the forebrain and the midbrain coordinate to control spatial attention. The critical involvement of the superior colliculus (SC)-the central structure in the midbrain network-in visuospatial attention has been shown by four seminal, published studies in monkeys (Macaca mulatta) performing multialternative tasks. However, due to the lack of a mechanistic framework for interpreting behavioral data in such tasks, the nature of the SC's contribution to attention remains unclear. Here we present and validate a novel decision framework for analyzing behavioral data in multialternative attention tasks. We apply this framework to re-examine the behavioral evidence from these published studies. Our model is a multidimensional extension to signal detection theory that distinguishes between two major classes of attentional mechanisms: those that alter the quality of sensory information or "sensitivity," and those that alter the selective gating of sensory information or "choice bias." Model-based simulations and model-based analyses of data from these published studies revealed a converging pattern of results that indicated that choice-bias changes, rather than sensitivity changes, were the primary outcome of SC manipulation. Our results suggest that the SC contributes to attentional performance predominantly by generating a spatial choice bias for stimuli at a selected location, and that this bias operates downstream of forebrain mechanisms that enhance sensitivity. The findings lead to a testable mechanistic framework of how the midbrain and forebrain networks interact to control spatial attention. Attention involves the selection of the most relevant information for differential sensory processing and decision making. While the mechanisms by which attention alters sensory encoding (sensitivity control) are well studied, the mechanisms by which attention alters decisional weighting of sensory evidence (choice-bias control) are poorly understood. Here

Cannabinoid type 1 receptor ligands WIN 55,212-2 and AM 251 alter anxiety-like behaviors of marmoset monkeys in an open-field test.

PubMed

Cagni, Priscila; Barros, Marilia

2013-03-01

Cannabinoid type 1 receptors (CB1r) are an important modulatory site for emotional behavior. However, little is known on the effects of CB1r ligands on emotionality aspects of primates, even with their highly similar behavioral response and receptor density/distribution as humans. Thus, we analyzed the effects of the CB1r agonist WIN 55,212-2 (WIN; 1mg/kg) and the antagonist AM 251 (AM; 2mg/kg), systemically administered prior to a single brief (15 min) exposure to a novel open-field (OF) environment, on the behavior of individually tested adult black tufted-ear marmosets. Both WIN- and AM-treated subjects, compared to vehicle controls, had significantly lower rates of long (contact) calls and exploration, while higher levels of vigilance-related behaviors (scan/glance); these are indicators of anxiolysis in this setup. Changes in locomotion were not detected. However, in the vehicle and AM-groups, sojourn in the peripheral zone of the OF was significantly higher than in its central region. WIN-treated marmosets spent an equivalent amount of time in both zones. Therefore, activation or blockade CB1r function prior to a short and individual exposure to an unfamiliar environment exerted a significant and complex influence on different behavioral indicators of anxiety in these monkeys (i.e., a partially overlapping anxiolytic-like profile). AM 251, however, has no anxiolytic effect when the time spent in the center of the OF is considered. This is a major difference when compared to the WIN-treated group. Data were compared to the response profile reported in other pre-clinical (rodent) and clinical studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel Models of Visual Topographic Map Alignment in the Superior Colliculus

PubMed Central

El-Ghazawi, Tarek A.; Triplett, Jason W.

2016-01-01

The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses. In the visual system, many connections are organized topographically, which preserves the spatial order of the visual scene. The superior colliculus (SC) is a midbrain nucleus that integrates visual inputs from the retina and primary visual cortex (V1) to regulate goal-directed eye movements. In the SC, topographically organized inputs from the retina and V1 must be aligned to facilitate integration. Previously, we showed that retinal input instructs the alignment of V1 inputs in the SC in a manner dependent on spontaneous neuronal activity; however, the mechanism of activity-dependent instruction remains unclear. To begin to address this gap, we developed two novel computational models of visual map alignment in the SC that incorporate distinct activity-dependent components. First, a Correlational Model assumes that V1 inputs achieve alignment with established retinal inputs through simple correlative firing mechanisms. A second Integrational Model assumes that V1 inputs contribute to the firing of SC neurons during alignment. Both models accurately replicate in vivo findings in wild type, transgenic and combination mutant mouse models, suggesting either activity-dependent mechanism is plausible. In silico experiments reveal distinct behaviors in response to weakening retinal drive, providing insight into the nature of the system governing map alignment depending on the activity-dependent strategy utilized. Overall, we describe novel computational frameworks of visual map alignment that accurately model many aspects of the in vivo process and propose experiments to test them. PMID:28027309

Evaluating the operations underlying multisensory integration in the cat superior colliculus.

PubMed

Stanford, Terrence R; Quessy, Stephan; Stein, Barry E

2005-07-13

It is well established that superior colliculus (SC) multisensory neurons integrate cues from different senses; however, the mechanisms responsible for producing multisensory responses are poorly understood. Previous studies have shown that spatially congruent cues from different modalities (e.g., auditory and visual) yield enhanced responses and that the greatest relative enhancements occur for combinations of the least effective modality-specific stimuli. Although these phenomena are well documented, little is known about the mechanisms that underlie them, because no study has systematically examined the operation that multisensory neurons perform on their modality-specific inputs. The goal of this study was to evaluate the computations that multisensory neurons perform in combining the influences of stimuli from two modalities. The extracellular activities of single neurons in the SC of the cat were recorded in response to visual, auditory, and bimodal visual-auditory stimulation. Each neuron was tested across a range of stimulus intensities and multisensory responses evaluated against the null hypothesis of simple summation of unisensory influences. We found that the multisensory response could be superadditive, additive, or subadditive but that the computation was strongly dictated by the efficacies of the modality-specific stimulus components. Superadditivity was most common within a restricted range of near-threshold stimulus efficacies, whereas for the majority of stimuli, response magnitudes were consistent with the linear summation of modality-specific influences. In addition to providing a constraint for developing models of multisensory integration, the relationship between response mode and stimulus efficacy emphasizes the importance of considering stimulus parameters when inducing or interpreting multisensory phenomena.

Inferior gluteal artery pseudoaneurysm related to intramuscular injection

PubMed Central

Saad, Paulo Fernandes; Saad, Karen Ruggeri; Armstrong, Dinani Matoso Fialho de Oliveira; Soares, Bruno Leonardo de Freitas; de Almeida, Paulo Henrique Freitas; Razuk Filho, Álvaro

2014-01-01

INTRODUCTION Gluteal artery pseudoaneurysms are rare, yet the most common in cases involving the superior gluteal artery. Pseudoaneurysms of the inferior gluteal artery are uncommon and are often related to blunt or penetrating trauma, infections and fractures of the pelvis. PRESENTATION OF CASE The authors present a case of pseudoaneurysm of the inferior gluteal artery related to an iatrogenic injury due to intramuscular injection of medication, which was treated with selective embolization of the artery during angiography. DISCUSSION The most common manifestation of an inferior gluteal artery pseudoaneurysm is the presence of a painful mass in the buttock that may or may not be associated with neurological symptoms due to compression of the sciatic nerve. Ultrasound with color Doppler and computerized tomography with multi-detectors are useful non-invasive tools for diagnosis. However, both diagnosis and therapy are facilitated by catheter angiography. CONCLUSION This case cautions that although pseudoaneurysms are rare, pseudoaneurysms of the inferior gluteal artery require a high index of suspicion and careful physical examination by the physician in order to avoid misdiagnosis. It also illustrates the usefulness of a minimally invasive modality for treatment of these lesions. PMID:25506847

Amino Acid Concentrations in the Hamster Central Auditory System and Long-Term Effects of Intense Tone Exposure

PubMed Central

Godfrey, Donald A.; Kaltenbach, James A.; Chen, Kejian; Ilyas, Omer; Liu, Xiaochen; Licari, Frank; Sacks, Justin; McKnight, Darwin

2015-01-01

Exposure to intense sounds often leads to loss of hearing of environmental sounds and hearing of a monotonous tonal sound not actually present, a condition known as tinnitus. Chronic physiological effects of exposure to intense tones have been reported for animals and should be accompanied by chemical changes present at long times after the intense sound exposure. By using a microdissection mapping procedure combined with high-performance liquid chromatography (HPLC), we have measured concentrations of nine amino acids, including those used as neurotransmitters, in the cochlear nucleus, inferior colliculus, medial geniculate, and auditory cortex of hamsters 5 months after exposure to an intense tone, compared with control hamsters of the same age. No very large differences in amino acid concentrations were found between exposed and control hamsters. However, increases of glutamate and γ-aminobutyrate (GABA) in some parts of the inferior colliculus of exposed hamsters were statistically significant. The most consistent differences between exposed and control hamsters were higher aspartate and lower taurine concentrations in virtually all regions of exposed hamsters, which reached statistical significance in many cases. Although these amino acids are not considered likely neurotransmitters, they indirectly have roles in excitatory and inhibitory neurotransmission, respectively. Thus, there is evidence for small, widespread, long-term increases in excitatory transmission and decreases in inhibitory transmission after a level of acoustic trauma previously shown to produce hearing loss and tinnitus. PMID:22715056

Effect of antiprogestin ZK 98. 734 on the ovarian cycle, early pregnancy, and on its binding to progesterone receptors in the myometrium of marmoset Callithrix jacchus

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

Puri, C.P.; Kholkute, S.D.; Pongubala, J.M.

1988-04-01

The antiprogestin ZK 98.734 (11 beta-(4-dimethylaminophenyl-17 beta-hydroxy-17 alpha-(3-hydroxy-prop-1(Z)-enyl-4,9(10)-estradien-3-one) was administered i.m. (5 mg/day) for three consecutive days to two groups of common marmosets. In one group (nonpregnant, n = 6), it was injected during the luteal phase, and to the second group (pregnant, n = 7), it was injected during early pregnancy, on Days 24-26 of the mid-cycle estradiol peak. Administration of ZK 98.734 during the luteal phase caused a sharp drop in plasma progesterone levels. The luteal phase was shortened whether the drug was administered during the early or the late luteal phase. Similarly, administration of ZK 98.734 duringmore » early pregnancy caused a significant drop in progesterone levels, and pregnancy was terminated in all of the animals. The post-treatment cycles in both groups of animals were ovulatory and of normal duration. /sup 3/H-ZK 98.734 showed specific binding to myometrial cytosol fraction. ZK 98.734 also displaced the binding of /sup 3/H-progesterone to progesterone receptors. However, progesterone had higher binding affinity than did ZK 98.734. The antifertility action of ZK 98.734 could be a result either of its luteolytic action or of its blocking the progesterone receptors in the target tissue. This study, therefore, indicates that in the common marmoset ZK 98.734 is a progesterone antagonist with a potential to terminate early pregnancy.« less

The synaptic pharmacology underlying sensory processing in the superior colliculus.

PubMed

Binns, K E

1999-10-01

The superior colliculus (SC) is one of the most ancient regions of the vertebrate central sensory system. In this hub afferents from several sensory pathways converge, and an extensive range of neural circuits enable primary sensory processing, multi-sensory integration and the generation of motor commands for orientation behaviours. The SC has a laminar structure and is usually considered in two parts; the superficial visual layers and the deep multi-modal/motor layers. Neurones in the superficial layers integrate visual information from the retina, cortex and other sources, while the deep layers draw together data from many cortical and sub-cortical sensory areas, including the superficial layers, to generate motor commands. Functional studies in anaesthetized subjects and in slice preparations have used pharmacological tools to probe some of the SC's interacting circuits. The studies reviewed here reveal important roles for ionotropic glutamate receptors in the mediation of sensory inputs to the SC and in transmission between the superficial and deep layers. N-methyl-D-aspartate receptors appear to have special responsibility for the temporal matching of retinal and cortical activity in the superficial layers and for the integration of multiple sensory data-streams in the deep layers. Sensory responses are shaped by intrinsic inhibitory mechanisms mediated by GABA(A) and GABA(B) receptors and influenced by nicotinic acetylcholine receptors. These sensory and motor-command activities of SC neurones are modulated by levels of arousal through extrinsic connections containing GABA, serotonin and other transmitters. It is possible to naturally stimulate many of the SC's sensory and non-sensory inputs either independently or simultaneously and this brain area is an ideal location in which to study: (a) interactions between inputs from the same sensory system; (b) the integration of inputs from several sensory systems; and (c) the influence of non-sensory systems on

Inferior ectopic pupil and typical ocular coloboma in RCS rats.

PubMed

Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

2011-08-01

Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F(1) rats nor N(2) (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma.

Inferior Ectopic Pupil and Typical Ocular Coloboma in RCS Rats

PubMed Central

Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

2011-01-01

Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F1 rats nor N2 (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma. PMID:22330254

Mapping of somatostatin-28 (1-12) in the alpaca (Lama pacos) brainstem.

PubMed

De Souza, Eliana; Sánchez, Manuel Lisardo; Aguilar, Luís Ángel; Díaz-Cabiale, Zaida; Narváez, José Ángel; Coveñas, Rafael

2015-05-01

Using an indirect immunoperoxidase technique, we studied the distribution of cell bodies and fibers containing somatostatin-28 (1-12) in the alpaca brainstem. Immunoreactive fibers were widely distributed throughout the whole brainstem: 34 brainstem nuclei/regions showed a high or a moderate density of these fibers. Perikarya containing the peptide were widely distributed throughout the mesencephalon, pons and medulla oblongata. Cell bodies containing somatostatin-28 (1-12) were observed in the lateral and medial divisions of the marginal nucleus of the brachium conjunctivum, reticular formation (mesencephalon, pons and medulla oblongata), inferior colliculus, periaqueductal gray, superior colliculus, pericentral division of the dorsal tegmental nucleus, interpeduncular nucleus, nucleus of the trapezoid body, vestibular nucleus, motor dorsal nucleus of the vagus, nucleus of the solitary tract, nucleus praepositus hypoglossi, and in the substantia nigra. This widespread distribution indicates that somatostatin-28 (1-12) is involved in multiple physiological actions in the alpaca brainstem. © 2015 Wiley Periodicals, Inc.

A spiking neural network model of the midbrain superior colliculus that generates saccadic motor commands.

PubMed

Kasap, Bahadir; van Opstal, A John

2017-08-01

Single-unit recordings suggest that the midbrain superior colliculus (SC) acts as an optimal controller for saccadic gaze shifts. The SC is proposed to be the site within the visuomotor system where the nonlinear spatial-to-temporal transformation is carried out: the population encodes the intended saccade vector by its location in the motor map (spatial), and its trajectory and velocity by the distribution of firing rates (temporal). The neurons' burst profiles vary systematically with their anatomical positions and intended saccade vectors, to account for the nonlinear main-sequence kinematics of saccades. Yet, the underlying collicular mechanisms that could result in these firing patterns are inaccessible to current neurobiological techniques. Here, we propose a simple spiking neural network model that reproduces the spike trains of saccade-related cells in the intermediate and deep SC layers during saccades. The model assumes that SC neurons have distinct biophysical properties for spike generation that depend on their anatomical position in combination with a center-surround lateral connectivity. Both factors are needed to account for the observed firing patterns. Our model offers a basis for neuronal algorithms for spatiotemporal transformations and bio-inspired optimal controllers.

Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset.

PubMed

Jackson, Stacey A W; Horst, Nicole K; Pears, Andrew; Robbins, Trevor W; Roberts, Angela C

2016-07-01

Two learning mechanisms contribute to decision-making: goal-directed actions and the "habit" system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior. © The Author 2016. Published by Oxford University Press.

Dopamine, but not serotonin, regulates reversal learning in the marmoset caudate nucleus

PubMed Central

Clarke, H. F.; Hill, G. J.; Robbins, T. W.; Roberts, A. C.

2011-01-01

Studies of visual discrimination reversal learning have revealed striking neurochemical dissociations at the level of the orbitofrontal cortex (OFC) with serotoninergic, but not dopaminergic integrity being important for successful reversal learning. These findings have considerable implications for disorders such as obsessive compulsive disorder and schizophrenia in which reversal learning is impaired, and are primarily treated with drugs targeting the dopaminergic and serotoninergic systems. Dysfunction in such disorders however, is not limited to the OFC and extends subcortically to other structures implicated in reversal learning, such as the medial caudate nucleus. Therefore, because the roles of the serotonin and dopamine within the caudate nucleus are poorly understood, this study compared the effects of selective serotoninergic or selective dopaminergic depletions of the marmoset medial caudate nucleus on serial discrimination reversal learning. All monkeys were able to learn novel stimulus-reward associations, but unlike control monkeys and monkeys with selective serotoninergic medial caudate depletions, dopamine-depleted monkeys were markedly impaired in their ability to reverse this association. This impairment was not perseverative in nature. These findings are the opposite of those seen in the OFC and provide evidence for a neurochemical double dissociation between the OFC and medial caudate in the regulation of reversal learning. Whilst the specific contributions of these monoamines within the OFC-striatal circuit remain to be elucidated, these findings have profound implications for the development of drugs designed to remediate some of the cognitive processes underlying impaired reversal learning. PMID:21411670

Synaptogenesis in retino-receptive layers of the superior colliculus of the opossum Didelphis marsupialis.

PubMed

Correa-Gillieron, E M; Cavalcante, L A

1999-08-01

The maturation of the neuropil and synapse formation were examined in the retino-receptive layers of the superior colliculus (SCr-r) in the opossum from a period prior to the onset of arborization of retinocollicular fibers (postnatal day 22 - P22), at 44% of the coecal period (CP), to the end of the fast phase of optic fiber myelination and weaning time (P81 - 118% CP). Development of the SCr-r neuropil follows a protracted time course and can be divided into three broad stages, which are characterized by (I) Large extracellular spaces, numerous growth cones that participate rarely in synaptic junctions, vesicles-poor immature synapses (P22-P30), (II) Synapses of varied morphology with abundant synaptic vesicles, and small terminals with dark mitochondria and round synaptic vesicles (RSD terminals) synapsing mostly onto dendritic shafts, flat-vesicles (F) terminals (P40-P56), (III) Sequential appearance of retinal (R) and pleomorphic-vesicles (P) terminals and of RSD terminals synapsing onto spine or spine-like processes, appearance of glomerulus-like synaptic arrays (synaptic islets) (P61-P81). The advancement of synaptogenesis in SCr-r from stage I to II and from stage II to III correlates closely with the differentiation of astrocytes and oligodendrocytes, respectively.

Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus).

PubMed

Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

2013-04-01

Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50 , were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals' lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. © 2013 Crown copyright. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

A basic review on the inferior alveolar nerve block techniques.

PubMed

Khalil, Hesham

2014-01-01

The inferior alveolar nerve block is the most common injection technique used in dentistry and many modifications of the conventional nerve block have been recently described in the literature. Selecting the best technique by the dentist or surgeon depends on many factors including the success rate and complications related to the selected technique. Dentists should be aware of the available current modifications of the inferior alveolar nerve block techniques in order to effectively choose between these modifications. Some operators may encounter difficulty in identifying the anatomical landmarks which are useful in applying the inferior alveolar nerve block and rely instead on assumptions as to where the needle should be positioned. Such assumptions can lead to failure and the failure rate of inferior alveolar nerve block has been reported to be 20-25% which is considered very high. In this basic review, the anatomical details of the inferior alveolar nerve will be given together with a description of its both conventional and modified blocking techniques; in addition, an overview of the complications which may result from the application of this important technique will be mentioned.

A basic review on the inferior alveolar nerve block techniques

PubMed Central

Khalil, Hesham

2014-01-01

The inferior alveolar nerve block is the most common injection technique used in dentistry and many modifications of the conventional nerve block have been recently described in the literature. Selecting the best technique by the dentist or surgeon depends on many factors including the success rate and complications related to the selected technique. Dentists should be aware of the available current modifications of the inferior alveolar nerve block techniques in order to effectively choose between these modifications. Some operators may encounter difficulty in identifying the anatomical landmarks which are useful in applying the inferior alveolar nerve block and rely instead on assumptions as to where the needle should be positioned. Such assumptions can lead to failure and the failure rate of inferior alveolar nerve block has been reported to be 20-25% which is considered very high. In this basic review, the anatomical details of the inferior alveolar nerve will be given together with a description of its both conventional and modified blocking techniques; in addition, an overview of the complications which may result from the application of this important technique will be mentioned. PMID:25886095

Neural correlates of target selection for reaching movements in superior colliculus

PubMed Central

McPeek, Robert M.

2014-01-01

We recently demonstrated that inactivation of the primate superior colliculus (SC) causes a deficit in target selection for arm-reaching movements when the reach target is located in the inactivated field (Song JH, Rafal RD, McPeek RM. Proc Natl Acad Sci USA 108: E1433–E1440, 2011). This is consistent with the notion that the SC is part of a general-purpose target selection network beyond eye movements. To understand better the role of SC activity in reach target selection, we examined how individual SC neurons in the intermediate layers discriminate a reach target from distractors. Monkeys reached to touch a color oddball target among distractors while maintaining fixation. We found that many SC neurons robustly discriminate the goal of the reaching movement before the onset of the reach even though no saccade is made. To identify these cells in the context of conventional SC cell classification schemes, we also recorded visual, delay-period, and saccade-related responses in a delayed saccade task. On average, SC cells that discriminated the reach target from distractors showed significantly higher visual and delay-period activity than nondiscriminating cells, but there was no significant difference in saccade-related activity. Whereas a majority of SC neurons that discriminated the reach target showed significant delay-period activity, all nondiscriminating cells lacked such activity. We also found that some cells without delay-period activity did discriminate the reach target from distractors. We conclude that the majority of intermediate-layer SC cells discriminate a reach target from distractors, consistent with the idea that the SC contains a priority map used for effector-independent target selection. PMID:25505107

Variant Inferior Alveolar Nerves and Implications for Local Anesthesia

PubMed Central

Wolf, Kevin T.; Brokaw, Everett J.; Bell, Andrea; Joy, Anita

2016-01-01

A sound knowledge of anatomical variations that could be encountered during surgical procedures is helpful in avoiding surgical complications. The current article details anomalous morphology of inferior alveolar nerves encountered during routine dissection of the craniofacial region in the Gross Anatomy laboratory. We also report variations of the lingual nerves, associated with the inferior alveolar nerves. The variations were documented and a thorough review of literature was carried out. We focus on the variations themselves, and the clinical implications that these variations present. Thorough understanding of variant anatomy of the lingual and inferior alveolar nerves may determine the success of procedural anesthesia, the etiology of pathologic processes, and the avoidance of surgical misadventure. PMID:27269666

Non-inferiority cancer clinical trials: scope and purposes underlying their design.

PubMed

Riechelmann, R P; Alex, A; Cruz, L; Bariani, G M; Hoff, P M

2013-07-01

Non-inferiority clinical trials (NIFCTs) aim to demonstrate that the experimental therapy has advantages over the standard of care, with acceptable loss of efficacy. We evaluated the purposes underlying the selection of a non-inferiority design in oncology and the size of their non-inferiority margins (NIFm's). All NIFCTs of cancer-directed therapies and supportive care agents published in a 10-year period were eligible. Two investigators extracted the data and independently classified the trials by their purpose to choose a non-inferiority design. Seventy-five were included: 43% received funds from industry, overall survival was the most common primary end point and 73% reported positive results. The most frequent purposes underlying the selection of a non-inferiority design were to test more conveniently administered schedules and/or less toxic treatments. In 13 (17%) trials, a clear purpose was not identified. Among the trials that reported a pre-specified NIFm, the median value was 12.5% (range 4%-25%) for trials with binary primary end points and Hazard Ratio of 1.25 (range 1.10-1.50) for trials that used time-to-event primary outcomes. Cancer NIFCT harbor serious methodological and ethical issues. Many use large NIFm and nearly one-fifth did not state a clear purpose for selecting a non-inferiority design.

Inferior vena cava filters.

PubMed

Duffett, L; Carrier, M

2017-01-01

Use of inferior vena cava (IVC) filters has increased dramatically in recent decades, despite a lack of evidence that their use has impacted venous thromboembolism (VTE)-related mortality. This increased use appears to be primarily driven by the insertion of retrievable filters for prophylactic indications. A growing body of evidence, however, suggests that IVC filters are frequently associated with clinically important adverse events, prompting a closer look at their role. We sought to narratively review the current evidence on the efficacy and safety of IVC filter placements. Inferior vena cava filters remain the only treatment option for patients with an acute (within 2-4 weeks) proximal deep vein thrombosis (DVT) or pulmonary embolism and an absolute contraindication to anticoagulation. In such patients, anticoagulation should be resumed and IVC filters removed as soon as the contraindication has passed. For all other indications, there is insufficient evidence to support the use of IVC filters and high-quality trials are required. In patients where an IVC filter remains, regular follow-up to reassess removal and screen for filter-related complications should occur. © 2016 International Society on Thrombosis and Haemostasis.

A proof of concept phase II non-inferiority criterion.

PubMed

Neuenschwander, Beat; Rouyrre, Nicolas; Hollaender, Norbert; Zuber, Emmanuel; Branson, Michael

2011-06-15

Traditional phase III non-inferiority trials require compelling evidence that the treatment vs control effect bfθ is better than a pre-specified non-inferiority margin θ(NI) . The standard approach compares this margin to the 95 per cent confidence interval of the effect parameter. In the phase II setting, in order to declare Proof of Concept (PoC) for non-inferiority and proceed in the development of the drug, different criteria that are specifically tailored toward company internal decision making may be more appropriate. For example, less evidence may be needed as long as the effect estimate is reasonably convincing. We propose a non-inferiority design that addresses the specifics of the phase II setting. The requirements are that (1) the effect estimate be better than a critical threshold θ(C), and (2) the type I error with regard to θ(NI) is controlled at a pre-specified level. This design is compared with the traditional design from a frequentist as well as a Bayesian perspective, where the latter relies on the Level of Proof (LoP) metric, i.e. the probability that the true effect is better than effect values of interest. Clinical input is required to establish the value θ(C), which makes the design transparent and improves interactions within clinical teams. The proposed design is illustrated for a non-inferiority trial for a time-to-event endpoint in oncology. Copyright © 2011 John Wiley & Sons, Ltd.

The effects of inferior olive lesion on strychnine seizure

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

Anderson, M.C.; Chung, E.Y.; Van Woert, M.H.

1990-10-01

Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable ({sup 3}H)AMPA ((RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid) binding in cerebella from inferior olive-lesioned rats was observed, but no difference in ({sup 3}H)AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10 imine) were tested asmore » anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the ({sup 3}H)AMPA binding data.« less

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

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

Churchill, L.; Pazdernik, T.L.; Jackson, J.L.

1984-08-01

(3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturationmore » curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.« less

Flibanserin stimulated partner grooming reflects brain metabolism changes in female marmosets

PubMed Central

Converse, Alexander K.; Aubert, Yves; Allers, Kelly A.; Sommer, Bernd; Abbott, David H.

2017-01-01

Introduction Female Sexual Interest and Arousal Disorder (FSIAD) is personally distressing for women. To better understand the mechanism of the candidate therapeutic, flibanserin, we determined its effects on an index of brain glucose metabolism. Aim We hypothesized that chronic treatment with flibanserin would alter metabolism in brain regions associated with serotonergic function and female sexual behavior. Methods In a crossover design, eight adult female common marmosets (Calithrix jacchus) received daily flibanserin or vehicle. After 7–12 weeks of treatment, the glucose metabolism radiotracer FDG was administered to each female immediately prior to 30 min of interaction with her male pairmate, after which females were anesthetized and imaged by PET. Whole-brain normalized images were analyzed with anatomically defined regions of interest. Whole brain voxelwise mapping was used to explore treatment effects. Correlations were examined between alterations in metabolism and pairmate social grooming. Main Outcome Measures Changes in metabolism associated with flibanserin were determined for dorsal raphe (DR), medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus (VMH), and field CA1 of hippocampus. Results In response to chronic flibanserin, metabolism in mPOA declined, and this reduction correlated with increases in pairmate grooming. A cluster of voxels in frontal cortico-limbic regions exhibited reduced metabolism in response to flibanserin and overlapped with a voxel cluster in which reductions in metabolism correlated with increases in pairmate grooming. Finally, reductions in mPOA metabolism correlated with increases in metabolism in a cluster of voxels in somatosensory cortex. Conclusions Taken together, these results suggest that flibanserin-induced reductions in female mPOA neural activity increase intimate affiliative behavior with male pairmates. PMID:26635207

Mapping the Primate Visual System with [2-14C]Deoxyglucose

NASA Astrophysics Data System (ADS)

Macko, Kathleen A.; Jarvis, Charlene D.; Kennedy, Charles; Miyaoka, Mikoto; Shinohara, Mami; Sokoloff, Louis; Mishkin, Mortimer

1982-10-01

The [2-14C]deoxyglucose method was used to identify the cerebral areas related to vision in the rhesus monkey (Macaca mulatta). This was achieved by comparing glucose utilization in a visually stimulated with that in a visually deafferented hemisphere. The cortical areas related to vision included the entire expanse of striate, prestriate, and inferior temporal cortex as far forward as the temporal pole, the posterior part of the inferior parietal lobule, and the prearcuate and inferior prefrontal cortex. Subcortically, in addition to the dorsal lateral geniculate nucleus and superficial layers of the superior colliculus, the structures related to vision included large parts of the pulvinar, caudate, putamen, claustrum, and amygdala. These results, which are consonant with a model of visual function that postulates an occipito-temporo-prefrontal pathway for object vision and an occipito-parieto-prefrontal pathway for spatial vision, reveal the full extent of those pathways and identify their points of contact with limbic, striatal, and diencephalic structures.

Surgical management of strabismus after rupture of the inferior rectus muscle.

PubMed

Paysse, E A; Saunders, R A; Coats, D K

2000-06-01

Rupture of an inferior rectus muscle is an uncommon problem. The resulting absence of infraduction and large hypertropia that result when the muscle cannot be repaired are challenging to manage surgically. We treated 2 patients who had traumatic rupture of the inferior rectus muscle. Both patients underwent an inferior transposition of the inferior halves of the medial and lateral rectus muscles without disinsertion (modified Jensen transposition procedure). Both patients had a persistent small overcorrection in the primary gaze position. One patient was treated with a second strabismus surgery consisting of a recession of the contralateral superior rectus muscle; the other was treated with prism glasses. Both achieved restoration of depression to approximately 40 degrees and single binocular vision in the primary position at distance, near, and in the reading position. This modified Jensen transposition procedure of the horizontal rectus muscles appears to be highly effective in the treatment of the hypertropia and infraduction deficit produced by rupture of the inferior rectus muscle. It also appears to be suitable for use in situations when other rectus muscles are absent or unavailable for surgical manipulation.

Endoscopic medial maxillectomy with preservation of inferior turbinate and nasolacrimal duct.

PubMed

Nakayama, Tsuguhisa; Asaka, Daiya; Okushi, Tetsushi; Yoshikawa, Mamoru; Moriyama, Hiroshi; Otori, Nobuyoshi

2012-01-01

Endoscopic medial maxillectomy (EMM) is a safe and effective procedure for treatment of inverted papilloma (IP) originating from the maxillary sinus. However, EMM usually removes the inferior turbinate and nasolacrimal duct. The inferior turbinate has a critical function in conditioning of the nasal airflow, and resection of the nasolacrimal ducts has a risk of epiphora. We developed a newly derived surgical technique, endoscopic modified medial maxillectomy (EMMM), which enables preservation of the inferior turbinate and nasolacrimal duct. A retrospective case series of six patients with IP and nine patients with mucoceles of the maxillary sinus after a Caldwell-Luc operation, who underwent surgery using the EMMM technique, were reviewed. In patients with IP, there were no recurrences for a mean follow-up of 16.7 months. Eight of nine patients with mucoceles of the maxillary sinus showed patency. All patients showed preservation of the inferior turbinate. One patient with mucocele was referred for dacryocystorhinostomy because of epiphora. EMMM produces access to the maxillary sinus identically to conventional EMM, despite preservation of the inferior turbinate and nasolacrimal duct.

Effects of Monobutyl and Di(n-butyl) Phthalate in Vitro on Steroidogenesis and Leydig Cell Aggregation in Fetal Testis Explants from the Rat: Comparison with Effects in Vivo in the Fetal Rat and Neonatal Marmoset and in Vitro in the Human

PubMed Central

Hallmark, Nina; Walker, Marion; McKinnell, Chris; Mahood, I. Kim; Scott, Hayley; Bayne, Rosemary; Coutts, Shiona; Anderson, Richard A.; Greig, Irene; Morris, Keith; Sharpe, Richard M.

2007-01-01

Background Certain phthalates can impair Leydig cell distribution and steroidogenesis in the fetal rat in utero, but it is unknown whether similar effects might occur in the human. Objectives Our aim in this study was to investigate the effects of di(n-butyl) phthalate (DBP), or its metabolite monobutyl phthalate (MBP), on testosterone production and Leydig cell aggregation (LCA) in fetal testis explants from the rat and human, and to compare the results with in vivo findings for DBP-exposed rats. We also wanted to determine if DBP/MBP affects testosterone production in vivo in the neonatal male marmoset. Methods Fetal testis explants obtained from the rat [gestation day (GD)19.5] and from the human (15–19 weeks of gestation) were cultured for 24–48 hr with or without human chorionic gonadotropin (hCG) or 22R-hydroxycholesterol (22R-OH), and with or without DBP/MBP. Pregnant rats and neonatal male marmosets were dosed with 500 mg/kg/day DBP or MBP. Results Exposure of rats in utero to DBP (500 mg/kg/day) for 48 hr before GD21.5 induced major suppression of intratesticular testosterone levels and cytochrome P450 side chain cleavage enzyme (P450scc) expression; this short-term treatment induced LCA, but was less marked than longer term (GD13.5–20.5) DBP treatment. In vitro, MBP (10−3 M) did not affect basal or 22R-OH-stimulated testosterone production by fetal rat testis explants but slightly attenuated hCG-stimulated steroidogenesis; MBP induced minor LCA in vitro. None of these parameters were affected in human fetal testis explants cultured with 10−3 M MBP for up to 48 hr. Because the in vivo effects of DBP/MBP were not reproduced in vitro in the rat, the absence of MBP effects in vitro on fetal human testes is inconclusive. In newborn (Day 2–7) marmosets, administration of a single dose of 500 mg/kg MBP significantly (p = 0.019) suppressed blood testosterone levels 5 hr later. Similar treatment of newborn co-twin male marmosets for 14 days resulted in

The macaque midbrain reticular formation sends side-specific feedback to the superior colliculus.

PubMed

Wang, Niping; Warren, Susan; May, Paul J

2010-04-01

The central mesencephalic reticular formation (cMRF) likely plays a role in gaze control, as cMRF neurons receive tectal input and provide a bilateral projection back to the superior colliculus (SC). We examined the important question of whether this feedback is excitatory or inhibitory. Biotinylated dextran amine (BDA) was injected into the cMRF of M. fascicularis monkeys to anterogradely label reticulotectal terminals and retrogradely label tectoreticular neurons. BDA labeled profiles in the ipsi- and contralateral intermediate gray layer (SGI) were examined electron microscopically. Postembedding GABA immunochemistry was used to identify putative inhibitory profiles. Nearly all (94.7%) of the ipsilateral BDA labeled terminals were GABA positive, but profiles postsynaptic to these labeled terminals were exclusively GABA negative. In addition, BDA labeled terminals were observed to contact BDA labeled dendrites, indicating the presence of a monosynaptic feedback loop connecting the cMRF and ipsilateral SC. In contrast, within the contralateral SGI, half of the BDA labeled terminals were GABA positive, while more than a third were GABA negative. All the postsynaptic profiles were GABA negative. These results indicate the cMRF provides inhibitory feedback to the ipsilateral side of the SC, but it has more complex effects on the contralateral side. The ipsilateral projection may help tune the "winner-take-all" mechanism that produces a unified saccade signal, while the contralateral projections may contribute to the coordination of activity between the two colliculi.

Significance of localization of mandibular foramen in an inferior alveolar nerve block.

PubMed

Thangavelu, K; Kannan, R; Kumar, N Senthil; Rethish, E; Sabitha, S; Sayeeganesh, N

2012-07-01

The mandibular foramen (MF) is an opening on the internal surface of the ramus for divisions of the mandibular vessels and nerve to pass. The aim of this study is to determine the position of the MF from various anatomical landmarks in several dry adult mandibles. A total of 102 human dry mandibles were examined, of which 93 were of dentulous and 9 were of edentulous. The measurements were taken from the anterior border of the ramus (coronoid notch) to the midportion of the MF and then from the midportion of the MF to the other landmarks such as internal oblique ridge, inferior border, sigmoid notch, and condyle were measured and recorded. The data were compared using Student's t-test. The MF is positioned at a mean distance of 19 mm (with SD 2.34) from coronoid notch of the anterior border of the ramus. Superio-inferiorly from the condyle to the inferior border MF is situated 5 mm inferior to the midpoint of condyle to the inferior border distance (ramus height). We conclude that failures in the anesthesia of the inferior alveolar nerve are due to the operator error and not due to the anatomical variation.

The Neural Substrate for Binaural Masking Level Differences in the Auditory Cortex

PubMed Central

Gilbert, Heather J.; Krumbholz, Katrin; Palmer, Alan R.

2015-01-01

The binaural masking level difference (BMLD) is a phenomenon whereby a signal that is identical at each ear (S0), masked by a noise that is identical at each ear (N0), can be made 12–15 dB more detectable by inverting the waveform of either the tone or noise at one ear (Sπ, Nπ). Single-cell responses to BMLD stimuli were measured in the primary auditory cortex of urethane-anesthetized guinea pigs. Firing rate was measured as a function of signal level of a 500 Hz pure tone masked by low-passed white noise. Responses were similar to those reported in the inferior colliculus. At low signal levels, the response was dominated by the masker. At higher signal levels, firing rate either increased or decreased. Detection thresholds for each neuron were determined using signal detection theory. Few neurons yielded measurable detection thresholds for all stimulus conditions, with a wide range in thresholds. However, across the entire population, the lowest thresholds were consistent with human psychophysical BMLDs. As in the inferior colliculus, the shape of the firing-rate versus signal-level functions depended on the neurons' selectivity for interaural time difference. Our results suggest that, in cortex, BMLD signals are detected from increases or decreases in the firing rate, consistent with predictions of cross-correlation models of binaural processing and that the psychophysical detection threshold is based on the lowest neural thresholds across the population. PMID:25568115

Auditory Midbrain Implant: Research and Development Towards a Second Clinical Trial

PubMed Central

Lim, Hubert H.; Lenarz, Thomas

2015-01-01

The cochlear implant is considered one of the most successful neural prostheses to date, which was made possible by visionaries who continued to develop the cochlear implant through multiple technological and clinical challenges. However, patients without a functional auditory nerve or implantable cochlea cannot benefit from a cochlear implant. The focus of the paper is to review the development and translation of a new type of central auditory prosthesis for this group of patients, which is known as the auditory midbrain implant (AMI) and is designed for electrical stimulation within the inferior colliculus. The rationale and results for the first AMI clinical study using a multi-site single-shank array will be presented initially. Although the AMI has achieved encouraging results in terms of safety and improvements in lip-reading capabilities and environmental awareness, it has not yet provided sufficient speech perception. Animal and human data will then be presented to show that a two-shank AMI array can potentially improve hearing performance by targeting specific neurons of the inferior colliculus. Modifications to the AMI array design, stimulation strategy, and surgical approach have been made that are expected to improve hearing performance in the patients implanted with a two-shank array in an upcoming clinical trial funded by the National Institutes of Health. Positive outcomes from this clinical trial will motivate new efforts and developments toward improving central auditory prostheses for those who cannot sufficiently benefit from cochlear implants. PMID:25613994

Forebrain pathway for auditory space processing in the barn owl.

PubMed

Cohen, Y E; Miller, G L; Knudsen, E I

1998-02-01

The forebrain plays an important role in many aspects of sound localization behavior. Yet, the forebrain pathway that processes auditory spatial information is not known for any species. Using standard anatomic labeling techniques, we used a "top-down" approach to trace the flow of auditory spatial information from an output area of the forebrain sound localization pathway (the auditory archistriatum, AAr), back through the forebrain, and into the auditory midbrain. Previous work has demonstrated that AAr units are specialized for auditory space processing. The results presented here show that the AAr receives afferent input from Field L both directly and indirectly via the caudolateral neostriatum. Afferent input to Field L originates mainly in the auditory thalamus, nucleus ovoidalis, which, in turn, receives input from the central nucleus of the inferior colliculus. In addition, we confirmed previously reported projections of the AAr to the basal ganglia, the external nucleus of the inferior colliculus (ICX), the deep layers of the optic tectum, and various brain stem nuclei. A series of inactivation experiments demonstrated that the sharp tuning of AAr sites for binaural spatial cues depends on Field L input but not on input from the auditory space map in the midbrain ICX: pharmacological inactivation of Field L eliminated completely auditory responses in the AAr, whereas bilateral ablation of the midbrain ICX had no appreciable effect on AAr responses. We conclude, therefore, that the forebrain sound localization pathway can process auditory spatial information independently of the midbrain localization pathway.

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

Significance of localization of mandibular foramen in an inferior alveolar nerve block

PubMed Central

Thangavelu, K.; Kannan, R.; Kumar, N. Senthil; Rethish, E.; Sabitha, S.; SayeeGanesh, N.

2012-01-01

Background: The mandibular foramen (MF) is an opening on the internal surface of the ramus for divisions of the mandibular vessels and nerve to pass. The aim of this study is to determine the position of the MF from various anatomical landmarks in several dry adult mandibles. Materials and Methods: A total of 102 human dry mandibles were examined, of which 93 were of dentulous and 9 were of edentulous. The measurements were taken from the anterior border of the ramus (coronoid notch) to the midportion of the MF and then from the midportion of the MF to the other landmarks such as internal oblique ridge, inferior border, sigmoid notch, and condyle were measured and recorded. Results: The data were compared using Student's t-test. The MF is positioned at a mean distance of 19 mm (with SD 2.34) from coronoid notch of the anterior border of the ramus. Superio-inferiorly from the condyle to the inferior border MF is situated 5 mm inferior to the midpoint of condyle to the inferior border distance (ramus height). Conclusion: We conclude that failures in the anesthesia of the inferior alveolar nerve are due to the operator error and not due to the anatomical variation. PMID:23225978

Dynamic Analysis of Gene Expression in Rice Superior and Inferior Grains by RNA-Seq

PubMed Central

Sun, Hongzheng; Peng, Ting; Zhao, Yafan; Du, Yanxiu; Zhang, Jing; Li, Junzhou; Xin, Zeyu; Zhao, Quanzhi

2015-01-01

Poor grain filling of inferior grains located on lower secondary panicle branch causes great drop in rice yield and quality. Dynamic gene expression patterns between superior and inferior grains were examined from the view of the whole transcriptome by using RNA-Seq method. In total, 19,442 genes were detected during rice grain development. Genes involved in starch synthesis, grain storage and grain development were interrogated in particular in superior and inferior grains. Of the genes involved in sucrose to starch transformation process, most were expressed at lower level in inferior grains at early filling stage compared to that of superior grains. But at late filling stage, the expression of those genes was higher in inferior grains and lower in superior grains. The same trends were observed in the expression of grain storage protein genes. While, evidence that genes involved in cell cycle showed higher expression in inferior grains during whole period of grain filling indicated that cell proliferation was active till the late filling stage. In conclusion, delayed expression of most starch synthesis genes in inferior grains and low capacity of sink organ might be two important factors causing low filling rate of inferior grain at early filling stage, and shortage of carbohydrate supply was a limiting factor at late filling stage. PMID:26355995

Inferior oblique muscle paresis as a sign of myasthenia gravis.

PubMed

Almog, Yehoshua; Ben-David, Merav; Nemet, Arie Y

2016-03-01

Myasthenia gravis may affect any of the six extra-ocular muscles, masquerading as any type of ocular motor pathology. The frequency of involvement of each muscle is not well established in the medical literature. This study was designed to determine whether a specific muscle or combination of muscles tends to be predominantly affected. This retrospective review included 30 patients with a clinical diagnosis of myasthenia gravis who had extra-ocular muscle involvement with diplopia at presentation. The diagnosis was confirmed by at least one of the following tests: Tensilon test, acetylcholine receptor antibodies, thymoma on chest CT scan, or suggestive electromyography. Frequency of involvement of each muscle in this cohort was inferior oblique 19 (63.3%), lateral rectus nine (30%), superior rectus four (13.3%), inferior rectus six (20%), medial rectus four (13.3%), and superior oblique three (10%). The inferior oblique was involved more often than any other muscle (p<0.01). Eighteen (60%) patients had ptosis, six (20%) of whom had bilateral ptosis. Diagnosing myasthenia gravis can be difficult, because the disease may mimic every pupil-sparing pattern of ocular misalignment. In addition diplopia caused by paresis of the inferior oblique muscle is rarely encountered (other than as a part of oculomotor nerve palsy). Hence, when a patient presents with vertical diplopia resulting from an isolated inferior oblique palsy, myasthenic etiology should be highly suspected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thickening of the inferior glenohumeral capsule: an ultrasound sign for shoulder capsular contracture.

PubMed

Michelin, Paul; Delarue, Yohann; Duparc, Fabrice; Dacher, Jean Nicolas

2013-10-01

The aim of this retrospective study was to measure the inferior glenohumeral capsule thickness of shoulders clinically affected by capsular contracture by comparison to the contralateral asymptomatic side. Bilateral shoulder ultrasound (US) examinations of 20 patients with clinically or MRI proven unilateral capsular contracture were retrospectively assessed. Inferior capsule evaluation was performed with a transducer placed within the axilla in maximally abducted shoulders. Measurements were symmetrically performed orthogonally to the inferior glenohumeral ligament (IGHL) in the axial plane; the coronal plane was used to ensure the tension of the IGHL. The significance of any difference in thickening was assessed with the Mann-Whitney test. The average thickness was 4.0 mm in shoulders with capsular contracture vs. 1.3 mm in asymptomatic contralateral shoulders (P < 0.0001). Twenty per cent of patients with capsular contracture and inferior capsule thickness increase showed US features of other painful diseases of the rotator cuff. The thickness of the inferior capsule is measurable through ultrasound examination and appears to be increased in shoulders with capsular contracture. Exploration of the inferior aspect of the shoulder joint could be added to shoulder US examination protocols for capsular contracture assessment even if other rotator cuff abnormalities are diagnosed by US. • Ultrasound is increasingly used to diagnose shoulder problems. • The thickness of the inferior glenohumeral ligament is measurable in the axilla. • The inferior glenohumeral ligament appears thickened in shoulders with capsular contracture. • Capsular contracture ultrasound features can be associated with other rotator cuff problems.

Release of the Inferior Crus in Antihelix Plasty.

PubMed

Raunig, Hermann; Ofner, Michael

2016-07-01

Protruding ears with a hypoplastic antihelix often have poorly developed inferior cura. Publications on this topic until now have only dealt with absent inferior crus and have neglected its importance in everyday antihelix plasty. This article describes a new surgical technique to improve treatment of the antihelix. Patients with protruding upper third ears received either standard otoplasty with crus superior remodeling (ST) or the newly developed surgical procedure including crus inferior release (STI). To evaluate the results, a survey containing 10 questions about different outcome parameters was conducted with the patients. Each question was given a score ranging from 0 to 10, where 10 meant the best outcome and 0 the worst. From January 2013 to March 2014, 216 patients underwent otoplasty, of which 99 completed the questionnaire. No differences could be found between ST and STI patients except for their duration of pain, which was significantly less in group STI. Overall, the scores from the questionnaire were 89.85 in ST and 92.35 in STI. Mean values for satisfaction were 9.33 in group ST and 9.56 in group STI. When correcting the antihelix, the inferior crus must always be checked because the protruding upper third cannot be compensated only by overcorrecting the superior crus. It should be a matter of routine to recognize the degree of malformation and determine the best possible treatment. This novel technique is an additional valuable option in otoplasty to improve the upper third in a more natural way and create highly satisfactory results. © The Author(s) 2016.

Superior-inferior position of patellar component affects patellofemoral kinematics and contact forces in computer simulation.

PubMed

Nakamura, Shinichiro; Tanaka, Yoshihisa; Kuriyama, Shinichi; Nishitani, Kohei; Ito, Hiromu; Furu, Moritoshi; Matsuda, Shuichi

2017-06-01

Anterior knee pain has been reported as a major postoperative complication after total knee arthroplasty, which may lead to patient dissatisfaction. Rotational alignment and the medial-lateral position correlate with patellar maltracking, which can cause knee pain postoperatively. However, the superior-inferior position of the patellar component has not been investigated. The purpose of the current study was to investigate the effects of the patellar superior-inferior position on patellofemoral kinematics and kinetics. Superior, central, and inferior models with a dome patellar component were constructed. In the superior and inferior models, the position of the patellar component translated superiorly and inferiorly, respectively, by 3mm, relative to the center model. Kinematics of the patellar component, quadriceps force, and patellofemoral contact force were calculated using a computer simulation during a squatting activity in a weight-bearing deep knee bend. In the inferior model, the flexion angle, relative to the tibial component, was the greatest among all models. The inferior model showed an 18.0%, 36.5%, and 22.7% increase in the maximum quadriceps force, the maximum medial patellofemoral force, and the maximum lateral patellofemoral force, respectively, compared with the superior model. Superior-inferior positions affected patellofemoral kinematic and kinetics. Surgeons should avoid the inferior position of the patellar component, because the inferior positioned model showed greater quadriceps and patellofemoral force, resulting in a potential risk for anterior knee pain and component loosening. Copyright © 2017. Published by Elsevier Ltd.

Cross-sectional echocardiographic diagnosis of azygos continuation of the inferior vena cava.

PubMed

Huhta, J C; Smallhorn, J F; Macartney, F J

1984-01-01

Azygos continuation of the inferior vena cava has importance for both the invasive diagnosis of congenital heart disease by catheterization and for surgical treatment. Cross-sectional echocardiography was used to examine 1,000 patients (1 day to 16 years, mean 3.3 years) who also had angiographic or surgical confirmation. Twenty-eight patients (3%) had azygos continuation (left 13, right 14, bilateral 1) and, in 26 patients, the hepatic portion of the inferior vena cava was absent. Azygos continuation was prospectively detected in all and was directly visualized in subcostal scans as a venous structure posterior to the aorta coursing behind the heart and not entering the inferior aspect of either atrium in 26/28 (93%). Azygos connection to the ipsilateral superior vena cava or atrium was correctly predicted in all. The inferior vena cava was visualized in all patients without azygos continuation, except one neonate with omphalocele. We conclude that cross-sectional echocardiography can accurately detect azygos continuation of the inferior vena cava and predict its side and connection.

Prolactin's Mediative Role in Male Parenting in Parentally Experienced Marmosets (Callithrix jacchus)

PubMed Central

Ziegler, Toni E.; Prudom, Shelley L.; Zahed, Sofia Refetoff; Parlow, A. F.; Wegner, Fredrick

2009-01-01

Prolactin has been implicated in promoting paternal care behaviors but little evidence of causality has been found to date except for birds and fish. This study was designed to examine the possible causal relationships between prolactin and male parenting behaviors, reproductive hormones, and physical changes in cooperatively breeding common marmosets, Callithrix jacchus. Fifteen parentally experienced fathers were studied over three consecutive infant care periods during two weeks prior and three weeks following their mates' parturition under three treatment conditions: normal control pregnancy, decreased prolactin and elevated prolactin. The treatments significantly altered the serum prolactin levels in the fathers. Using three methods of determining a father's level of parental care: infant carrying, family effort and responsiveness to infant stimulus tests, we found that only the male response to infant stimuli was altered by the hormone treatments. Lowering prolactin significantly reduced male responsiveness to infant stimuli but elevating prolactin showed the same effect. Hormonal sampling indicated that testosterone levels showed an inverse relationship to prolactin levels during a normal peripartum period and prolactin treatment reduced this relationship. Prepartum estradiol levels were significantly elevated during the lowered prolactin treatment and estradiol was significantly lowered postpartum with the elevated prolactin treatment. Father's weight decreased significantly by the third week of infant care during the normal treatment. Males in the elevated prolactin treatment lost little or no weight from prepartum while in the lowered prolactin treatment showed the most weight loss. The present findings did not distinguish a direct causal relationship of prolactin on behavior in experienced fathers but did find an interaction with other hormones and weight gain. PMID:19664636

Patterns of developmental expression of the RNA editing enzyme rADAR2.

PubMed

Paupard M-C; O'Connell, M A; Gerber, A P; Zukin, R S

2000-01-01

To date, two structurally related RNA-editing enzymes with adenosine deaminase activity have been identified in mammalian tissue: ADAR1 and ADAR2 [Bass B. I. et al. (1997) RNA 3, 947-949]. In rodents, ADAR2 undergoes alternative RNA splicing, giving rise to two splice variants that differ by the presence or absence of a 10-amino-acid insert in the carboxy-terminal catalytic domain. However, the physiological significance of the splicing and its regional and developmental regulation are as yet unknown. The present study examined spatial and temporal patterns of ADAR2 gene transcripts within specific neuronal populations of rat brain. The two rodent ADAR2 isoforms were expressed at comparable levels at all ages examined. rADAR2 messenger RNA expression was first detectable in the thalamic nuclei formation at embryonic day E19. The rADAR2b insert and rADAR2a splice probes produced images similar to that of the rADAR2 pan probe. At birth, rADAR2a messenger RNA splice variants were abundantly expressed in the thalamic nuclei. No signal for any probe was detectable in other brain regions, including neocortex, hippocampus, striatum and cerebellum at this stage of development. During the first week of postnatal life, rADAR2 messenger RNA expression (detected with the pan probe) increased gradually in several brain regions, with low expression detected at postnatal day P7 in the olfactory bulb, inferior colliculus, and within the pyramidal and granule cell layers of the hippocampus. Hybridization patterns of the rADAR2a variant probe reached peak expression at about the second week of life, while peak expression of the rADAR2b probe was reached at about the third week of life. At the end of the first week of life (P7), expression of both splice variants was strongest in the thalamic nuclei. By P14, rADAR2 messenger RNA expression was more consolidated in the deeper structures, including the thalamic nuclei and the granule cell layer of the cerebellum. By P21, maximal levels

Active integration of glutamatergic input to the inferior olive generates bidirectional postsynaptic potentials

PubMed Central

Garden, Derek L. F.; Rinaldi, Arianna

2016-01-01

Key points We establish experimental preparations for optogenetic investigation of glutamatergic input to the inferior olive.Neurones in the principal olivary nucleus receive monosynaptic extra‐somatic glutamatergic input from the neocortex.Glutamatergic inputs to neurones in the inferior olive generate bidirectional postsynaptic potentials (PSPs), with a fast excitatory component followed by a slower inhibitory component.Small conductance calcium‐activated potassium (SK) channels are required for the slow inhibitory component of glutamatergic PSPs and oppose temporal summation of inputs at intervals ≤ 20 ms.Active integration of synaptic input within the inferior olive may play a central role in control of olivo‐cerebellar climbing fibre signals. Abstract The inferior olive plays a critical role in motor coordination and learning by integrating diverse afferent signals to generate climbing fibre inputs to the cerebellar cortex. While it is well established that climbing fibre signals are important for motor coordination, the mechanisms by which neurones in the inferior olive integrate synaptic inputs and the roles of particular ion channels are unclear. Here, we test the hypothesis that neurones in the inferior olive actively integrate glutamatergic synaptic inputs. We demonstrate that optogenetically activated long‐range synaptic inputs to the inferior olive, including projections from the motor cortex, generate rapid excitatory potentials followed by slower inhibitory potentials. Synaptic projections from the motor cortex preferentially target the principal olivary nucleus. We show that inhibitory and excitatory components of the bidirectional synaptic potentials are dependent upon AMPA (GluA) receptors, are GABAA independent, and originate from the same presynaptic axons. Consistent with models that predict active integration of synaptic inputs by inferior olive neurones, we find that the inhibitory component is reduced by blocking large conductance

Inferior vena cava filter penetration following Whipple surgical procedure causing ureteral injury.

PubMed

Abdel-Aal, Ahmed Kamel; Ezzeldin, Islam B; Moustafa, Amr Soliman; Ertel, Nathan; Oser, Rachel

2015-12-01

We report a case of an indwelling inferior vena cava filter that penetrated the IVC wall after Whipple's pancreatico-duodenectomy procedure performed in a patient with ampullary carcinoma, resulting in right ureteral injury and obstruction with subsequent hydroureter and hydronephrosis. This was incidentally discovered on a computed tomography scan performed as routine follow up to evaluate the results of the surgery. We retrieved the inferior vena cava filter and placed a nephrostomy catheter to relieve the ureteral obstruction. Our case highlights the importance of careful inferior vena cava manipulation during abdominal surgery in the presence of an inferior vena cava filter, and the option of temporary removal of the filter to be placed again after surgery in order to avoid this complication, unless protection is required against clot migration during the surgical procedure.

Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity

PubMed Central

Shaikh, Aasef G.; Hong, Simon; Liao, Ke; Tian, Jing; Solomon, David; Zee, David S.; Leigh, R. John

2010-01-01

The inferior olivary nuclei clearly play a role in creating oculopalatal tremor, but the exact mechanism is unknown. Oculopalatal tremor develops some time after a lesion in the brain that interrupts inhibition of the inferior olive by the deep cerebellar nuclei. Over time the inferior olive gradually becomes hypertrophic and its neurons enlarge developing abnormal soma-somatic gap junctions. However, results from several experimental studies have confounded the issue because they seem inconsistent with a role for the inferior olive in oculopalatal tremor, or because they ascribe the tremor to other brain areas. Here we look at 3D binocular eye movements in 15 oculopalatal tremor patients and compare their behaviour to the output of our recent mathematical model of oculopalatal tremor. This model has two mechanisms that interact to create oculopalatal tremor: an oscillator in the inferior olive and a modulator in the cerebellum. Here we show that this dual mechanism model can reproduce the basic features of oculopalatal tremor and plausibly refute the confounding experimental results. Oscillations in all patients and simulations were aperiodic, with a complicated frequency spectrum showing dominant components from 1 to 3 Hz. The model’s synchronized inferior olive output was too small to induce noticeable ocular oscillations, requiring amplification by the cerebellar cortex. Simulations show that reducing the influence of the cerebellar cortex on the oculomotor pathway reduces the amplitude of ocular tremor, makes it more periodic and pulse-like, but leaves its frequency unchanged. Reducing the coupling among cells in the inferior olive decreases the oscillation’s amplitude until they stop (at ∼20% of full coupling strength), but does not change their frequency. The dual-mechanism model accounts for many of the properties of oculopalatal tremor. Simulations suggest that drug therapies designed to reduce electrotonic coupling within the inferior olive or

Detecting and accounting for violations of the constancy assumption in non-inferiority clinical trials.

PubMed

Koopmeiners, Joseph S; Hobbs, Brian P

2018-05-01

Randomized, placebo-controlled clinical trials are the gold standard for evaluating a novel therapeutic agent. In some instances, it may not be considered ethical or desirable to complete a placebo-controlled clinical trial and, instead, the placebo is replaced by an active comparator with the objective of showing either superiority or non-inferiority to the active comparator. In a non-inferiority trial, the experimental treatment is considered non-inferior if it retains a pre-specified proportion of the effect of the active comparator as represented by the non-inferiority margin. A key assumption required for valid inference in the non-inferiority setting is the constancy assumption, which requires that the effect of the active comparator in the non-inferiority trial is consistent with the effect that was observed in previous trials. It has been shown that violations of the constancy assumption can result in a dramatic increase in the rate of incorrectly concluding non-inferiority in the presence of ineffective or even harmful treatment. In this paper, we illustrate how Bayesian hierarchical modeling can be used to facilitate multi-source smoothing of the data from the current trial with the data from historical studies, enabling direct probabilistic evaluation of the constancy assumption. We then show how this result can be used to adapt the non-inferiority margin when the constancy assumption is violated and present simulation results illustrating that our method controls the type-I error rate when the constancy assumption is violated, while retaining the power of the standard approach when the constancy assumption holds. We illustrate our adaptive procedure using a non-inferiority trial of raltegravir, an antiretroviral drug for the treatment of HIV.

Detecting and Accounting for Violations of the Constancy Assumption in Non-Inferiority Clinical Trials

PubMed Central

Koopmeiners, Joseph S.; Hobbs, Brian P.

2016-01-01

Randomized, placebo-controlled clinical trials are the gold standard for evaluating a novel therapeutic agent. In some instances, it may not be considered ethical or desirable to complete a placebo-controlled clinical trial and, instead, the placebo is replaced by an active comparator (AC) with the objective of showing either superiority or non-inferiority to the AC. In a non-inferiority trial, the experimental treatment is considered non-inferior if it retains a pre-specified proportion of the effect of the AC as represented by the non-inferiority margin. A key assumption required for valid inference in the non-inferiority setting is the constancy assumption, which requires that the effect of the AC in the non-inferiority trial is consistent with the effect that was observed in previous trials. It has been shown that violations of the constancy assumption can result in a dramatic increase in the rate of incorrectly concluding non-inferiority in the presence of ineffective or even harmful treatment. In this paper, we illustrate how Bayesian hierarchical modeling can be used to facilitate multi-source smoothing of the data from the current trial with the data from historical studies, enabling direct probabilistic evaluation of the constancy assumption. We then show how this result can be used to adapt the non-inferiority margin when the constancy assumption is violated and present simulation results illustrating that our method controls the type-I error rate when the constancy assumption is violated, while retaining the power of the standard approach when the constancy assumption holds. We illustrate our adaptive procedure using a non-inferiority trial of raltegravir, an antiretroviral drug for the treatment of HIV. PMID:27587591

When play is a family business: adult play, hierarchy, and possible stress reduction in common marmosets.

PubMed

Norscia, Ivan; Palagi, Elisabetta

2011-04-01

Easy to recognize but not easy to define, animal play is a baffling behavior because it has no obvious immediate benefits for the performers. However, the absence of immediate advantages, if true, would leave adult play (costly but maintained by evolution, spanning lemurs to Homo sapiens) unexplained. Although a commonly held view maintains that play is limited by stress, an emergent hypothesis states that play can regulate stress in the short term. Here we explored this hypothesis in a captive family group of New World monkeys, Callithrix jacchus (common marmoset). We observed six subjects and gathered data on aggressive, play, and scratching behavior via focal (6 h/individual) and all occurrences sampling (115 h). We found that play levels were highest during pre-feeding, the period of maximum anxiety due to the forthcoming competition over food. Scratching (the most reliable indicator of stress in primates) and play showed opposite trends along hierarchy, with dominants scratching more and playing less than subordinates. Finally, scratching decreased after play, whereas play appeared to be unrelated to previous scratching events, symptoms of a potential stressful state. In conclusion, both play timing and hierarchical distribution indicate that play limits stress, more than vice versa, at least in the short term.

Graded versus ungraded inferior oblique anterior transposition in patients with asymmetric dissociated vertical deviation.

PubMed

Rajavi, Zhale; Feizi, Mohadeseh; Naderi, Ali; Sabbaghi, Hamideh; Behradfar, Narges; Yaseri, Mehdi; Faghihi, Mohammad

2017-12-01

To report the surgical outcomes of graded versus ungraded inferior oblique anterior transposition (IOAT) in treatment of patients with asymmetric dissociated vertical deviation (DVD) and bilateral inferior oblique overaction (IOOA). A total of 74 eyes of 37 patients with asymmetric DVD (interocular difference of ≥5 Δ ) and bilateral IOOA of > +1 were included in this randomized clinical trial. In the ungraded group (n = 18), both inferior oblique muscles were sutured at the inferior rectus level; in the graded group (n = 19), the inferior oblique muscles of eyes with more DVD were sutured at the level of the inferior rectus and inferior oblique muscles of eyes with less DVD were sutured 2 mm posterior to the level of the inferior rectus muscle. DVD was significantly reduced in each group (P < 0.001 for both). Although the postoperative mean difference of asymmetry of DVD was less in the ungraded group compared to the graded group (1.2 ± 1.9 vs 3.2 ± 1.2 [P = 0.001]), the absolute amounts of reduction of DVD asymmetry were similar (4.3 ± 2.3 vs 4.4 ± 3.1 [P = 0.78]). IOOA and V patterns were also reduced postoperatively. Each method of IOAT was effective in reducing DVD, asymmetry, IOOA, and V patterns. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

The ABC of non-inferiority margin setting from indirect comparisons.

PubMed

Julious, Steven A

2011-01-01

In a non-inferiority trial to assess a new investigative treatment, there may need to be consideration of an indirect comparison with placebo using the active control in the current trial. We can, therefore, use the fact that there is a common active control in the comparisons of the investigative treatment and placebo. In analysing a non-inferiority trial, the ABC of: Assay sensitivity, Bias minimisation and Constancy assumption needs to be considered. It is highlighted how the ABC assumptions can potentially fail when there is placebo creep or a patient population shift. In this situation, the belief about the placebo response expressed in terms of a prior probability in Bayesian formulation could be used with the observed treatment effects to set the non-inferiority limit. Copyright © 2011 John Wiley & Sons, Ltd.

Simulation of the Inferior Mirage

ERIC Educational Resources Information Center

Branca, Mario

2010-01-01

A mirage can occur when a continuous variation in the refractive index of the air causes light rays to follow a curved path. As a result, the image we see is displaced from the location of the object. If the image appears higher in the air than the object, it is called a "superior" mirage, while if it appears lower it is called an "inferior"…

Indications, complications and outcomes of inferior vena cava filters: A retrospective study.

PubMed

Wassef, Andrew; Lim, Wendy; Wu, Cynthia

2017-05-01

Inferior vena cava filters are used to prevent embolization of a lower extremity deep vein thrombosis when the risk of pulmonary embolism is thought to be high. However, evidence is lacking for their benefit and guidelines differ on the recommended indications for filter insertion. The study aim was to determine the reasons for inferior vena cava filter placement and subsequent complication rate. A retrospective cohort of patients receiving inferior vena cava filters in Edmonton, Alberta, Canada from 2007 to 2011. Main outcome was the indication of inferior vena cava filter insertion. Other measures include baseline demographic and medical history of patients, clinical outcomes and filter retrieval rates. 464 patients received inferior vena cava filters. An acute deep vein thrombosis with a contraindication to anticoagulation was the indication for 206 (44.4%) filter insertions. No contraindication to anticoagulation could be identified in 20.7% of filter placements. 30.6% were placed in those with active cancer, in which mortality was significantly higher. Only 38.9% of retrievable filters were successfully retrieved. Inferior vena cava filters were placed frequently in patients with weak or no guideline-supported indications for filter placement and in up to 20% of patients with no contraindication to anticoagulation. The high rates of cancer and the high mortality rate of the cohort raise the possibility that some filters are placed inappropriately in end of life settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

A case of residual inferior sinus venosus defect after ineffective surgical closure.

PubMed

Uga, Sayuri; Hidaka, Takayuki; Takasaki, Taiichi; Kihara, Yasuki

2014-10-03

A 38-year-old woman presented with cyanosis and heart failure 34 years after patch closure of an atrial septal defect and partial anomalous pulmonary venous connection. CT and cardiac catheterisation showed a residual defect that caused right-to-left shunting. The patch almost blocked the inferior vena cava from the right atrium, resulting in uncommon drainage of the inferior vena cava into the left atrium. Other anomalies included the coronary-to-pulmonary artery fistula and duplicate inferior vena cava with dilated azygos venous system. A second surgery was performed, and we confirmed an inferior sinus venosus defect, which is rare and can be misdiagnosed. The ineffective patch closure had caused a haemodynamic status that rarely occurs. We describe the diagnostic process and emphasise the importance of correctly understanding the entity. 2014 BMJ Publishing Group Ltd.

Neurotransmitter involvement in development and maintenance of the auditory space map in the guinea pig superior colliculus.

PubMed

Ingham, N J; Thornton, S K; McCrossan, D; Withington, D J

1998-12-01

Neurotransmitter involvement in development and maintenance of the auditory space map in the guinea pig superior colliculus. J. Neurophysiol. 80: 2941-2953, 1998. The mammalian superior colliculus (SC) is a complex area of the midbrain in terms of anatomy, physiology, and neurochemistry. The SC bears representations of the major sensory modalites integrated with a motor output system. It is implicated with saccade generation, in behavioral responses to novel sensory stimuli and receives innervation from diverse regions of the brain using many neurotransmitter classes. Ethylene-vinyl acetate copolymer (Elvax-40W polymer) was used here to deliver chronically neurotransmitter receptor antagonists to the SC of the guinea pig to investigate the potential role played by the major neurotransmitter systems in the collicular representation of auditory space. Slices of polymer containing different drugs were implanted onto the SC of guinea pigs before the development of the SC azimuthal auditory space map, at approximately 20 days after birth (DAB). A further group of animals was exposed to aminophosphonopentanoic acid (AP5) at approximately 250 DAB. Azimuthal spatial tuning properties of deep layer multiunits of anesthetized guinea pigs were examined approximately 20 days after implantation of the Elvax polymer. Broadband noise bursts were presented to the animals under anechoic, free-field conditions. Neuronal responses were used to construct polar plots representative of the auditory spatial multiunit receptive fields (MURFs). Animals exposed to control polymer could develop a map of auditory space in the SC comparable with that seen in unimplanted normal animals. Exposure of the SC of young animals to AP5, 6-cyano-7-nitroquinoxaline-2,3-dione, or atropine, resulted in a reduction in the proportion of spatially tuned responses with an increase in the proportion of broadly tuned responses and a degradation in topographic order. Thus N-methyl--aspartate (NMDA) and non

Whisker motor cortex reorganization after superior colliculus output suppression in adult rats.

PubMed

Veronesi, Carlo; Maggiolini, Emma; Franchi, Gianfranco

2013-10-01

The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS-evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1-3 weeks). The ICMS-evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS-evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short-term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS-evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Fiber Tracts of the Medial and Inferior Surfaces of the Cerebrum.

PubMed

Baydin, Serhat; Gungor, Abuzer; Tanriover, Necmettin; Baran, Oguz; Middlebrooks, Erik H; Rhoton, Albert L

2017-02-01

Fiber dissection studies of the cerebrum have focused on the lateral surface. No comparable detailed studies have been done on the medial and inferior surfaces. The object of this study was to examine the fiber tracts, cortical, and subcortical structures of the medial and inferior aspects of the brain important in planning operative approaches along the interhemispheric fissure, parafalcine area, and basal surfaces of the cerebrum. Twenty formalin-fixed human hemispheres (10 brains) were examined by fiber dissection technique under ×6-×40 magnifications. The superior longitudinal fasciculus I, cingulum, inferior longitudinal fasciculus, uncinate fasciculus, optic radiations, tapetum, and callosal fibers were dissected step by step from medial to lateral, exposing the nucleus accumbens, subthalamic nucleus, red nucleus, and central midline structures (fornix, stria medullaris, and stria terminalis). Finally, the central core structures were dissected from medial to lateral. Understanding the fiber network underlying the medial and inferior aspects of the brain is important in surgical planning for approaches along the interhemispheric fissure, parafalcine area, and basal surfaces of the cerebrum. Copyright © 2016. Published by Elsevier Inc.

Correlation between remnant inferior turbinate volume and symptom severity of empty nose syndrome.

PubMed

Hong, Hye Ran; Jang, Yong Ju

2016-06-01

Empty nose syndrome (ENS) is an iatrogenic disorder caused by turbinate reduction procedures, which results in considerable nasal dysfunction and severely impaired quality of life. However, there is a lack of data that explains the relationship between the degree of turbinate reduction and subjective symptoms. The aim of this study was to evaluate the effects of remnant inferior turbinate volume on symptom severity. We retrospectively analyzed data from 34 patients who were diagnosed with ENS. All patients underwent computed tomography scanning and completed the SNOT-25 questionnaire. The control group consisted of 10 patients with pituitary adenoma who did not have any sinonasal symptoms or abnormalities. The inferior turbinate volumes were compared between groups, and the correlation between inferior turbinate volumes (ITVs) and Sino-Nasal Outcome Test-25 (SNOT-25) was also evaluated. The ENS group presented with a significantly smaller inferior turbinate volume than the control group (P < 0.001). The overall SNOT-25 score demonstrated no statistically significant correlation with anterior, posterior, or total ITV (P > 0.05, respectively). Among the various items on SNOT-25, a high dryness score was significantly correlated with a smaller total inferior turbinate volume (P = 0.030). Facial pain was significantly correlated with smaller anterior ITV (P = 0.011). In addition, patients who had smaller posterior inferior turbinate volume demonstrated higher scores on specific SNOT-25 items. A smaller inferior turbinate volume is significantly associated with specific SNOT-25 items in ENS patients. 4. Laryngoscope, 126:1290-1295, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Inferior tilt fixation of the glenoid component in reverse total shoulder arthroplasty: A biomechanical study.

PubMed

Chae, S W; Lee, J; Han, S H; Kim, S-Y

2015-06-01

Glenoid component fixation with an inferior tilt has been suggested to decrease scapular notching, but this remains controversial. We aimed here to evaluate the effect of glenoid component inferior tilt in reverse total shoulder arthroplasty (RSA) on micromotion and loss of fixation of the glenoid component by biomechanical testing. Increased inferior reaming of the glenoid for inferiorly tilted implantation of the glenoid component will decrease glenoid bone stock and compromise the fixation of RSA. The micromotions of the glenoid components attached to 14 scapulae from fresh frozen cadavers were measured and compared between neutral and 10° inferior tilts in 0.7- and 1-body weight cyclic loading tests using digital-image analysis. The incidence of bone breakage or loss of fixation was assessed in the 1-body weight fatigue-loading test. Micromotion was higher with a 10° inferior tilt than with a neutral tilt during both the 0.7-body weight (36 ± 11 μm vs. 22 ± 5 μm; P = 0.028) and 1-body weight (44 ± 16 μm vs. 28 ± 9 μm; P = 0.045) cyclic loading. The incidence of bone breakage or loss of fixation was 17% and 60% with a neutral and 10° inferior tilt, respectively. Glenoid component inferior tilt fixation in RSA may reduce primary stability and increase mechanical failure of the glenoid component, thereby reducing longevity of the prosthesis. Accordingly, we recommend careful placement of the glenoid component when an inferior tilt is used. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Task-relevant output signals are sent from monkey dorsolateral prefrontal cortex to the superior colliculus during a visuospatial working memory task.

PubMed

Johnston, Kevin; Everling, Stefan

2009-05-01

Visuospatial working memory is one of the most extensively investigated functions of the dorsolateral prefrontal cortex (DLPFC). Theories of prefrontal cortical function have suggested that this area exerts cognitive control by modulating the activity of structures to which it is connected. Here, we used the oculomotor system as a model in which to characterize the output signals sent from the DLPFC to a target structure during a classical spatial working memory task. We recorded the activity of identified DLPFC-superior colliculus (SC) projection neurons while monkeys performed a memory-guided saccade task in which they were required to generate saccades toward remembered stimulus locations. DLPFC neurons sent signals related to all aspects of the task to the SC, some of which were spatially tuned. These data provide the first direct evidence that the DLPFC sends task-relevant information to the SC during a spatial working memory task, and further support a role for the DLPFC in the direct modulation of other brain areas.

Abstract Representations of Object-Directed Action in the Left Inferior Parietal Lobule.

PubMed

Chen, Quanjing; Garcea, Frank E; Jacobs, Robert A; Mahon, Bradford Z

2018-06-01

Prior neuroimaging and neuropsychological research indicates that the left inferior parietal lobule in the human brain is a critical substrate for representing object manipulation knowledge. In the present functional MRI study we used multivoxel pattern analyses to test whether action similarity among objects can be decoded in the inferior parietal lobule independent of the task applied to objects (identification or pantomime) and stimulus format in which stimuli are presented (pictures or printed words). Participants pantomimed the use of objects, cued by printed words, or identified pictures of objects. Classifiers were trained and tested across task (e.g., training data: pantomime; testing data: identification), stimulus format (e.g., training data: word format; testing format: picture) and specific objects (e.g., training data: scissors vs. corkscrew; testing data: pliers vs. screwdriver). The only brain region in which action relations among objects could be decoded across task, stimulus format and objects was the inferior parietal lobule. By contrast, medial aspects of the ventral surface of the left temporal lobe represented object function, albeit not at the same level of abstractness as actions in the inferior parietal lobule. These results suggest compulsory access to abstract action information in the inferior parietal lobe even when simply identifying objects.

INTERDEPENDENT SUPERIORITY AND INFERIORITY FEELINGS

PubMed Central

Ingham, Harrington V.

1949-01-01

It is postulated that in neurotic persons who have unrealistic feelings of superiority and inferiority the two are interdependent. This is a departure from the concept of previous observers that either one or the other is primary and its opposite is overcompensation. The author postulates considerable parallelism, with equal importance for each. He submits that the neurotic person forms two logic-resistant compartments for the two opposed self-estimates and that treatment which makes inroads of logic upon one compartment, simultaneously does so upon the other. Two examples are briefly reported. The neurotic benefits sought in exaggeration of capability are the same as those sought in insistence upon inferiority: Presumption of superiority at once bids for approbation and delivers the subject from the need to prove himself worthy of it in dreaded competition; exaggeration of incapability baits sympathy and makes competition unnecessary because failure is conceded. Some of the characteristics of abnormal self-estimates that distinguish them from normal are: Preoccupation with self, resistance to logical explanation of personality problems, inconsistency in reasons for beliefs in adequacy on the one hand and inadequacy on the other, unreality, rationalization of faults, and difficulty and vacillation in the selection of adequate goals. PMID:15390573

A rare congenital extrahepatic portosystemic shunt affecting the inferior mesenteric vein, inferior vena cava, and left ovarian vein.

PubMed

Takeuchi, Hajime; Takeda, Yoko; Takahashi, Miyo; Hayashi, Shogo; Fukuzawa, Yoshitaka; Nakano, Takashi

2014-09-01

To observe a case of congenital extrahepatic portosystemic shunt and discuss it from the embryological and clinical viewpoints. An 85-year-old female cadaver was employed for a dissection course at Aichi Medical University in 2009. There was no evidence of liver cirrhosis macroscopically or microscopically. A portosystemic shunt was observed that involved communication between the inferior mesenteric vein, inferior vena cava (IVC), and left ovarian vein by a single Y-shaped shunt vessel. To the best of our knowledge, this is the first reported case of the above-mentioned three veins being connected by a single Y-shaped shunt vessel. Considering the other venous diameters, the shunt appeared to flow into the splenic vein and IVC. It cannot be denied that this shunt may have led to hepatic encephalopathy, although the shunt effect may have been minimal. Embryological development of IVC appears to occur close to the plexus of anastomosing vitelline veins, forming the portal vein.

Heart block and cardiac embolization of fractured inferior vena cava filter.

PubMed

Abudayyeh, Islam; Takruri, Yessar; Weiner, Justin B

2016-01-01

A 66-year-old man underwent a placement of an inferior vena cava filter before a gastric surgery 9 years prior, presented to the emergency room with a complete atrioventricular block. Chest x-ray and transthoracic echocardiogram showed struts migrating to right ventricle with tricuspid regurgitation. Cardiothoracic surgery was consulted and declined an open surgical intervention due to the location of the embolized fragments and the patient's overall condition. It was also felt that the fragments had migrated chronically and were adhered to the cardiac structures. The patient underwent a dual-chamber permanent pacemaker implantation. Post-implant fluoroscopy showed no displacement of the inferior vena cava filter struts due to the pacemaker leads indicating that the filter fracture had likely been a chronic process. This case highlights a rare combination of complications related to inferior vena cava filter fractures and the importance of assessing for such fractures in chronic placements. Inferior vena cava filter placement for a duration greater than 1 month can be associated with filter fractures and strut migration which may lead to, although rare, serious or fatal complications such as complete atrioventricular conduction system disruption and valvular damage including significant tricuspid regurgitation. Assessing for inferior vena cava filter fractures in chronic filter placement is important to avoid such complications. When possible, retrieval of the filter should be considered in all patients outside the acute setting in order to avoid filter-related complications. Filter retrieval rates remain low even when a retrievable filter is in place and the patient no longer has a contraindication to anticoagulation.

Effects of pharmacological agents on subcortical resistance shifts

NASA Technical Reports Server (NTRS)

Klivington, K. A.

1975-01-01

Microliter quantities of tetrodotoxin, tetraethylammonium chloride, and picrotoxin injected into the inferior colliculus and superior olive of unanesthetized cats differentially affect the amplitude and waveform of click-evoked potentials and evoked resistance shifts. Tetrodotoxin simultaneously reduces the negative phase of the evoked potential and eliminates the evoked resistance shift. Tetraethylammonium enhances the negative evoked potential component, presumably of postsynaptic origin, without significantly altering evoked resistance shift amplitude. Picrotoxin also enhances the negative evoked potential wave but increases evoked resistance shift amplitude. These findings implicate events associated with postsynaptic membrane depolarization in the production of the evoked resistance shift.

The Non-Lemniscal Auditory Cortex in Ferrets: Convergence of Corticotectal Inputs in the Superior Colliculus

PubMed Central

Bajo, Victoria M.; Nodal, Fernando R.; Bizley, Jennifer K.; King, Andrew J.

2010-01-01

Descending cortical inputs to the superior colliculus (SC) contribute to the unisensory response properties of the neurons found there and are critical for multisensory integration. However, little is known about the relative contribution of different auditory cortical areas to this projection or the distribution of their terminals in the SC. We characterized this projection in the ferret by injecting tracers in the SC and auditory cortex. Large pyramidal neurons were labeled in layer V of different parts of the ectosylvian gyrus after tracer injections in the SC. Those cells were most numerous in the anterior ectosylvian gyrus (AEG), and particularly in the anterior ventral field, which receives both auditory and visual inputs. Labeling was also found in the posterior ectosylvian gyrus (PEG), predominantly in the tonotopically organized posterior suprasylvian field. Profuse anterograde labeling was present in the SC following tracer injections at the site of acoustically responsive neurons in the AEG or PEG, with terminal fields being both more prominent and clustered for inputs originating from the AEG. Terminals from both cortical areas were located throughout the intermediate and deep layers, but were most concentrated in the posterior half of the SC, where peripheral stimulus locations are represented. No inputs were identified from primary auditory cortical areas, although some labeling was found in the surrounding sulci. Our findings suggest that higher level auditory cortical areas, including those involved in multisensory processing, may modulate SC function via their projections into its deeper layers. PMID:20640247

Permanent nerve damage from inferior alveolar nerve blocks: a current update.

PubMed

Pogrel, M Anthony

2012-10-01

Permanent nerve involvement has been reported following inferior alveolar nerve blocks. This study provides an update on cases reported to one unit in the preceding six years. Lidocaine was associated with 25 percent of cases, articaine with 33 percent of cases, and prilocaine with 34 percent of cases. It does appear that inferior alveolar nerve blocks can cause permanent nerve damage with any local anesthetic, but the incidences may vary.

Importance of human right inferior frontoparietal network connected by inferior branch of superior longitudinal fasciculus tract in corporeal awareness of kinesthetic illusory movement.

PubMed

Amemiya, Kaoru; Naito, Eiichi

2016-05-01

It is generally believed that the human right cerebral hemisphere plays a dominant role in corporeal awareness, which is highly associated with conscious experience of the physical self. Prompted by our previous findings, we examined whether the right frontoparietal activations often observed when people experience kinesthetic illusory limb movement are supported by a large-scale brain network connected by a specific branch of the superior longitudinal fasciculus fiber tracts (SLF I, II, and III). We scanned brain activity with functional magnetic resonance imaging (MRI) while nineteen blindfolded healthy volunteers experienced illusory movement of the right stationary hand elicited by tendon vibration, which was replicated after the scanning. We also scanned brain activity when they executed and imagined right hand movement, and identified the active brain regions during illusion, execution, and imagery in relation to the SLF fiber tracts. We found that illusion predominantly activated the right inferior frontoparietal regions connected by SLF III, which were not substantially recruited during execution and imagery. Among these regions, activities in the right inferior parietal cortices and inferior frontal cortices showed right-side dominance and correlated well with the amount of illusion (kinesthetic illusory awareness) experienced by the participants. The results illustrated the predominant involvement of the right inferior frontoparietal network connected by SLF III when people recognize postural changes of their limb. We assume that the network bears a series of functions, specifically, monitoring the current status of the musculoskeletal system, and building-up and updating our postural model (body schema), which could be a basis for the conscious experience of the physical self. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Does the reduction of inferior turbinate affect lower airway functions?

PubMed

Unsal, Ozlem; Ozkahraman, Mehtap; Ozkarafakili, Mufide Arzu; Akpinar, Meltem; Korkut, Arzu Yasemin; Kurt Dizdar, Senem; Uslu Coskun, Berna

2017-11-06

Although the nose and lungs are separate organs, numerous studies have reported that the entire respiratory system can be considered as a single anatomical and functional unit. The upper and lower airways affect each other either directly or through reflex mechanisms. In this study, we aimed to evaluate the effects of the radiofrequency ablation of persistent inferior turbinate hypertrophy on nasal and pulmonary function. Twenty-seven patients with bilateral persistent inferior turbinate hypertrophy without septal deviation were included in this study. All of the patients were evaluated using anterior rhinoscopy, nasal endoscopy, acoustic rhinometry, a visual analogue scale, and flow-sensitive spirometry on the day before and 4 months after the radiofrequency ablation procedure. The post-ablation measurements revealed that the inferior turbinate ablation caused an increase in the mean cross-sectional area and volume of the nose, as well as in the forced expiratory volume in 1s, forced vital capacity, and peak expiratory flow of the patients. These differences between the pre- and post-ablation results were statistically significant. The post-ablation visual analogue scale scores were lower when compared with the pre-ablation scores, and this difference was also statistically significant. This study demonstrated that the widening of the nasal passage after the reduction of the inferior turbinate size had a favorable effect on the pulmonary function tests. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Inferior turbinate classification system, grades 1 to 4: development and validation study.

PubMed

Camacho, Macario; Zaghi, Soroush; Certal, Victor; Abdullatif, Jose; Means, Casey; Acevedo, Jason; Liu, Stanley; Brietzke, Scott E; Kushida, Clete A; Capasso, Robson

2015-02-01

To develop a validated inferior turbinate grading scale. Development and validation study. Phase 1 development (alpha test) consisted of a proposal of 10 different inferior turbinate grading scales (>1,000 clinic patients). Phase 2 validation (beta test) utilized 10 providers grading 27 standardized endoscopic photos of inferior turbinates using two different classification systems. Phase 3 validation (pilot study) consisted of 100 live consecutive clinic patients (n = 200 inferior turbinates) who were each prospectively graded by 18 different combinations of two independent raters, and grading was repeated by each of the same two raters, two separate times for each patient. In the development phase, 25% (grades 1-4) and 33% (grades 1-4) were the most useful systems. In the validation phase, the 25% classification system was found to be the best balance between potential clinical utility and ability to grade; the photo grading demonstrated a Cohen's kappa (κ) = 0.4671 ± 0.0082 (moderate inter-rater agreement). Live-patient grading with the 25% classification system demonstrated an overall inter-rater reliability of 71.5% (95% confidence interval [CI]: 64.8-77.3), with overall substantial agreement (κ = 0.704 ± 0.028). Intrarater reliability was 91.5% (95% CI: 88.7-94.3). Distribution for the 200 inferior turbinates was as follows: 25% quartile = grade 1, 50% quartile (median) = grade 2, 75% quartile = grade 3, and 90% quartile = grade 4. Mean turbinate size was 2.22 (95% CI: 2.07-2.34; standard deviation 1.02). Categorical κ was as follows: grade 1, 0.8541 ± 0.0289; grade 2, 0.7310 ± 0.0289; grade 3, 0.6997 ± 0.0289, and grade 4, 0.7760 ± 0.0289. The 25% (grades 1-4) inferior turbinate classification system is a validated grading scale with high intrarater and inter-rater reliability. This system can facilitate future research by tracking the effect of interventions on inferior turbinates. 2c. © 2014 The

Testing non-inferiority of a new treatment in three-arm clinical trials with binary endpoints.

PubMed

Tang, Nian-Sheng; Yu, Bin; Tang, Man-Lai

2014-12-18

A two-arm non-inferiority trial without a placebo is usually adopted to demonstrate that an experimental treatment is not worse than a reference treatment by a small pre-specified non-inferiority margin due to ethical concerns. Selection of the non-inferiority margin and establishment of assay sensitivity are two major issues in the design, analysis and interpretation for two-arm non-inferiority trials. Alternatively, a three-arm non-inferiority clinical trial including a placebo is usually conducted to assess the assay sensitivity and internal validity of a trial. Recently, some large-sample approaches have been developed to assess the non-inferiority of a new treatment based on the three-arm trial design. However, these methods behave badly with small sample sizes in the three arms. This manuscript aims to develop some reliable small-sample methods to test three-arm non-inferiority. Saddlepoint approximation, exact and approximate unconditional, and bootstrap-resampling methods are developed to calculate p-values of the Wald-type, score and likelihood ratio tests. Simulation studies are conducted to evaluate their performance in terms of type I error rate and power. Our empirical results show that the saddlepoint approximation method generally behaves better than the asymptotic method based on the Wald-type test statistic. For small sample sizes, approximate unconditional and bootstrap-resampling methods based on the score test statistic perform better in the sense that their corresponding type I error rates are generally closer to the prespecified nominal level than those of other test procedures. Both approximate unconditional and bootstrap-resampling test procedures based on the score test statistic are generally recommended for three-arm non-inferiority trials with binary outcomes.

Anterior inferior plating versus superior plating for clavicle fracture: a meta-analysis.

PubMed

Ai, Jie; Kan, Shun-Li; Li, Hai-Liang; Xu, Hong; Liu, Yang; Ning, Guang-Zhi; Feng, Shi-Qing

2017-04-18

The position of plate fixation for clavicle fracture remains controversial. Our objective was to perform a comprehensive review of the literature and quantify the surgical parameters and clinical indexes between the anterior inferior plating and superior plating for clavicle fracture. PubMed, EMBASE, and the Cochrane Library were searched for randomized and non-randomized studies that compared the anterior inferior plating with the superior plating for clavicle fracture. The relative risk or standardized mean difference with 95% confidence interval was calculated using either a fixed- or random-effects model. Four randomized controlled trials and eight observational studies were identified to compare the surgical parameters and clinical indexes. For the surgical parameters, the anterior inferior plating group was better than the superior plating group in operation time and blood loss (P < 0.05). Furthermore, in terms of clinical indexes, the anterior inferior plating was superior to the superior plating in reducing the union time, and the two kinds of plate fixation methods were comparable in constant score, and the rate of infection, nonunion, and complications (P > 0.05). Based on the current evidence, the anterior inferior plating may reduce the blood loss, the operation and union time, but no differences were observed in constant score, and the rate of infection, nonunion, and complications between the two groups. Given that some of the studies have low quality, more randomized controlled trails with high quality should be conduct to further verify the findings.

Different roles of axon guidance cues and patterned spontaneous activity in establishing receptive fields in the mouse superior colliculus.

PubMed

Liu, Mingna; Wang, Lupeng; Cang, Jianhua

2014-01-01

Visual neurons in the superior colliculus (SC) respond to both bright (On) and dark (Off) stimuli in their receptive fields. This receptive field property is due to proper convergence of On- and Off-centered retinal ganglion cells to their target cells in the SC. In this study, we have compared the receptive field structure of individual SC neurons in two lines of mutant mice that are deficient in retinotopic mapping: the ephrin-A knockouts that lack important retinocollicular axonal guidance cues and the nAChR-β2 knockouts that have altered activity-dependent refinement of retinocollicular projections. We find that even though the receptive fields are much larger in the ephrin-A knockouts, their On-Off overlap remains unchanged. These neurons also display normal level of selectivity for stimulus direction and orientation. In contrast, the On-Off overlap is disrupted in the β2 knockouts. Together with the previous finding of disrupted direction and orientation selectivity in the β2 knockout mice, our results indicate that molecular guidance cues and activity-dependent processes play different roles in the development of receptive field properties in the SC.

Divergence of dim-light vision among bats (order: Chiroptera) as estimated by molecular and electrophysiological methods.

PubMed

Liu, He-Qun; Wei, Jing-Kuan; Li, Bo; Wang, Ming-Shan; Wu, Rui-Qi; Rizak, Joshua D; Zhong, Li; Wang, Lu; Xu, Fu-Qiang; Shen, Yong-Yi; Hu, Xin-Tian; Zhang, Ya-Ping

2015-06-23

Dim-light vision is present in all bats, but is divergent among species. Old-World fruit bats (Pteropodidae) have fully developed eyes; the eyes of insectivorous bats are generally degraded, and these bats rely on well-developed echolocation. An exception is the Emballonuridae, which are capable of laryngeal echolocation but prefer to use vision for navigation and have normal eyes. In this study, integrated methods, comprising manganese-enhanced magnetic resonance imaging (MEMRI), f-VEP and RNA-seq, were utilized to verify the divergence. The results of MEMRI showed that Pteropodidae bats have a much larger superior colliculus (SC)/ inferior colliculus (IC) volume ratio (3:1) than insectivorous bats (1:7). Furthermore, the absolute visual thresholds (log cd/m(2)•s) of Pteropodidae (-6.30 and -6.37) and Emballonuridae (-3.71) bats were lower than those of other insectivorous bats (-1.90). Finally, genes related to the visual pathway showed signs of positive selection, convergent evolution, upregulation and similar gene expression patterns in Pteropodidae and Emballonuridae bats. Different results imply that Pteropodidae and Emballonuridae bats have more developed vision than the insectivorous bats and suggest that further research on bat behavior is warranted.

The source-filter theory of whistle-like calls in marmosets: Acoustic analysis and simulation of helium-modulated voices.

PubMed

Koda, Hiroki; Tokuda, Isao T; Wakita, Masumi; Ito, Tsuyoshi; Nishimura, Takeshi

2015-06-01

Whistle-like high-pitched "phee" calls are often used as long-distance vocal advertisements by small-bodied marmosets and tamarins in the dense forests of South America. While the source-filter theory proposes that vibration of the vocal fold is modified independently from the resonance of the supralaryngeal vocal tract (SVT) in human speech, a source-filter coupling that constrains the vibration frequency to SVT resonance effectively produces loud tonal sounds in some musical instruments. Here, a combined approach of acoustic analyses and simulation with helium-modulated voices was used to show that phee calls are produced principally with the same mechanism as in human speech. The animal keeps the fundamental frequency (f0) close to the first formant (F1) of the SVT, to amplify f0. Although f0 and F1 are primarily independent, the degree of their tuning can be strengthened further by a flexible source-filter interaction, the variable strength of which depends upon the cross-sectional area of the laryngeal cavity. The results highlight the evolutionary antiquity and universality of the source-filter model in primates, but the study can also explore the diversification of vocal physiology, including source-filter interaction and its anatomical basis in non-human primates.

Superior colliculus resting state networks in post-traumatic stress disorder and its dissociative subtype.

PubMed

Olivé, Isadora; Densmore, Maria; Harricharan, Sherain; Théberge, Jean; McKinnon, Margaret C; Lanius, Ruth

2018-01-01

The innate alarm system (IAS) models the neurocircuitry involved in threat processing in posttraumatic stress disorder (PTSD). Here, we investigate a primary subcortical structure of the IAS model, the superior colliculus (SC), where the SC is thought to contribute to the mechanisms underlying threat-detection in PTSD. Critically, the functional connectivity between the SC and other nodes of the IAS remains unexplored. We conducted a resting-state fMRI study to investigate the functional architecture of the IAS, focusing on connectivity of the SC in PTSD (n = 67), its dissociative subtype (n = 41), and healthy controls (n = 50) using region-of-interest seed-based analysis. We observed group-specific resting state functional connectivity between the SC for both PTSD and its dissociative subtype, indicative of dedicated IAS collicular pathways in each group of patients. When comparing PTSD to its dissociative subtype, we observed increased resting state functional connectivity between the left SC and the right dorsolateral prefrontal cortex (DLPFC) in PTSD. The DLPFC is involved in modulation of emotional processes associated with active defensive responses characterising PTSD. Moreover, when comparing PTSD to its dissociative subtype, increased resting state functional connectivity was observed between the right SC and the right temporoparietal junction in the dissociative subtype. The temporoparietal junction is involved in depersonalization responses associated with passive defensive responses typical of the dissociative subtype. Our findings suggest that unique resting state functional connectivity of the SC parallels the unique symptom profile and defensive responses observed in PTSD and its dissociative subtype. Hum Brain Mapp 39:563-574, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Transient delayed facial nerve palsy after inferior alveolar nerve block anesthesia.

PubMed

Tzermpos, Fotios H; Cocos, Alina; Kleftogiannis, Matthaios; Zarakas, Marissa; Iatrou, Ioannis

2012-01-01

Facial nerve palsy, as a complication of an inferior alveolar nerve block anesthesia, is a rarely reported incident. Based on the time elapsed, from the moment of the injection to the onset of the symptoms, the paralysis could be either immediate or delayed. The purpose of this article is to report a case of delayed facial palsy as a result of inferior alveolar nerve block, which occurred 24 hours after the anesthetic administration and subsided in about 8 weeks. The pathogenesis, treatment, and results of an 8-week follow-up for a 20-year-old patient referred to a private maxillofacial clinic are presented and discussed. The patient's previous medical history was unremarkable. On clinical examination the patient exhibited generalized weakness of the left side of her face with a flat and expressionless appearance, and she was unable to close her left eye. One day before the onset of the symptoms, the patient had visited her dentist for a routine restorative procedure on the lower left first molar and an inferior alveolar block anesthesia was administered. The patient's medical history, clinical appearance, and complete examinations led to the diagnosis of delayed facial nerve palsy. Although neurologic occurrences are rare, dentists should keep in mind that certain dental procedures, such as inferior alveolar block anesthesia, could initiate facial nerve palsy. Attention should be paid during the administration of the anesthetic solution.

The Incidence of Intravascular Needle Entrance during Inferior Alveolar Nerve Block Injection.

PubMed

Taghavi Zenouz, Ali; Ebrahimi, Hooman; Mahdipour, Masoumeh; Pourshahidi, Sara; Amini, Parisa; Vatankhah, Mahdi

2008-01-01

Dentists administer thousands of local anesthetic injections every day. Injection to a highly vascular area such as pterygomandibular space during an inferior alveolar nerve block has a high risk of intravascular needle entrance. Accidental intravascular injection of local anesthetic agent with vasoconstrictor may result in cardiovascular and central nervous system toxicity, as well as tachycardia and hypertension. There are reports that indicate aspiration is not performed in every injection. The aim of the present study was to assess the incidence of intravascular needle entrance in inferior alveolar nerve block injections. Three experienced oral and maxillofacial surgeons performed 359 inferior alveolar nerve block injections using direct or indirect techniques, and reported the results of aspiration. Aspirable syringes and 27 gauge long needles were used, and the method of aspiration was similar in all cases. Data were analyzed using t-test. 15.3% of inferior alveolar nerve block injections were aspiration positive. Intravascular needle entrance was seen in 14.2% of cases using direct and 23.3% of cases using indirect block injection techniques. Of all injections, 15.8% were intravascular on the right side and 14.8% were intravascular on the left. There were no statistically significant differences between direct or indirect block injection techniques (P = 0.127) and between right and left injection sites (P = 0.778). According to our findings, the incidence of intravascular needle entrance during inferior alveolar nerve block injection was relatively high. It seems that technique and maneuver of injection have no considerable effect in incidence of intravascular needle entrance.

Applied anatomy of the pterygomandibular space: improving the success of inferior alveolar nerve blocks.

PubMed

Khoury, J N; Mihailidis, S; Ghabriel, M; Townsend, G

2011-06-01

A thorough knowledge of the anatomy of the pterygomandibular space is essential for the successful administration of the inferior alveolar nerve block. In addition to the inferior alveolar and lingual nerves, other structures in this space are of particular significance for local anaesthesia, including the inferior alveolar vessels, the sphenomandibular ligament and the interpterygoid fascia. These structures can all potentially have an impact on the effectiveness of local anaesthesia in this area. Greater understanding of the nature and extent of variation in intraoral landmarks and underlying structures should lead to improved success rates, and provide safer and more effective anaesthesia. The direct technique for the inferior alveolar nerve block is used frequently by most clinicians in Australia and this review evaluates its anatomical rationale and provides possible explanations for anaesthetic failures. © 2011 Australian Dental Association.

Area 21a of cat visual cortex strongly modulates neuronal activities in the superior colliculus

PubMed Central

Hashemi-Nezhad, M; Wang, C; Burke, W; Dreher, B

2003-01-01

We have examined the influence of cortico-tectal projections from one of the pattern-processing extrastriate visual cortical areas, area 21a, on the responses to visual stimuli of single neurones in the superior colliculi of adult cats. For this purpose area 21a was briefly inactivated by cooling to 10 °C using a Peltier device. Responses to visual stimuli before and during cooling as well as after rewarming ipsilateral area 21a were compared. In addition, in a subpopulation of collicular neurones we have studied the effects of reversible inactivation of ipsilateral striate cortex (area 17, area V1). When area 21a was cooled, the temperature of area 17 was kept at 36 °C and vice versa. In the majority of cases (41/65; 63 %), irrespective of the velocity response profiles of collicular neurones, inactivation of area 21a resulted in a significant decrease in magnitude of responses of neurones in the ipsilateral colliculus and only in a small proportion of cells (2/65; 3.1 %) was there a significant increase in the magnitude of responses. Inactivation of area 21a resulted in significant changes in the magnitude of responses of collicular cells located not only in the retino-recipient layers but also in the stratum griseum intermediale. In most cases, reversible inactivation of area 17 resulted in a greater reduction in the magnitude of responses of collicular cells than inactivation of area 21a. Reversible inactivation of area 21a also affected the direction selectivity indices and length tuning of most collicular cells tested. PMID:12794178

Histologic consequences of inferior oblique anastomosis to denervated lateral rectus muscle.

PubMed

Christiansen, S; Madhat, M; Baker, R S

1987-01-01

Secondary muscular neurotization has been proposed as a means of restoring contractility to paretic extraocular muscle. We studied this technique by anastomosing healthy inferior oblique muscle to lateral rectus muscle that had been denervated either orbitally or intracranially in 20 dogs. Nerve and muscle fiber growth from the inferior oblique to the lateral rectus was demonstrated but no new neuromuscular junctions were formed. Regeneration of the lesioned sixth nerve occurred frequently and may explain the restoration of function claimed after this procedure.

Activity in the superior colliculus reflects dynamic interactions between voluntary and involuntary influences on orienting behaviour.

PubMed

Bell, Andrew H; Munoz, Douglas P

2008-10-01

Performance in a behavioural task can be influenced by both bottom-up and top-down processes such as stimulus modality and prior probability. Here, we exploited differences in behavioural strategy to explore the role of the intermediate and deep layers of the superior colliculus (dSC) in covert orienting. Two monkeys were trained on a predictive cued-saccade task in which the cue predicted the target's upcoming location with 80% validity. When the delay between cue and target onset was 250 ms, both monkeys showed faster responses to the uncued (Invalid) location. This was associated with a reduced target-aligned response in the dSC on Valid trials for both monkeys and is consistent with a bottom-up (i.e. involuntary) bias. When the delay was increased to 650 ms, one monkey continued to show faster responses to the Invalid location whereas the other monkey showed faster responses to the Valid location, consistent with a top-down (i.e. voluntary) bias. This latter behaviour was correlated with an increase in activity in dSC neurons preceding target onset that was absent in the other monkey. Thus, using the information provided by the cue shifted the emphasis towards top-down processing, while ignoring this information allowed bottom-up processing to continue to dominate. Regardless of the selected strategy, however, neurons in the dSC consistently reflected the current bias between the two processes, emphasizing its role in both the bottom-up and top-down control of orienting behaviour.

The history of the human female inferiority ideas in evolutionary biology.

PubMed

Bergman, Gerald

2002-01-01

A review of the prominent late 19th-century biological writings reveals that a major plank of early evolution theory was the belief that women were intellectually and physically inferior to men. Female inferiority was a logical conclusion of the Darwinian world view because males were believed to be exposed to far greater selective pressures than females, especially in war, competition for mates, food and clothing. Conversely, women were protected from selection by norms that required adult males provide for and protect women and children. Darwinists taught that as a result of this protection, natural selection operated far more actively on males than on females, producing male superiority in virtually all intellectual and skill areas. As a result, males became "more evolved" than women. The women inferiority doctrine is an excellent example of the fact that armchair logic often has been more important in building Darwinism than fossil and other empirical evidence.

Congenital anomalies of the inferior vena cava revealed on CT in patients with deep vein thrombosis.

PubMed

Gayer, G; Luboshitz, J; Hertz, M; Zissin, R; Thaler, M; Lubetsky, A; Bass, A; Korat, A; Apter, S

2003-03-01

We describe a possible relationship between inferior vena cava anomalies and extensive thrombosis of the inferior vena cava and the iliac and femoral veins. An anomaly of the inferior vena cava should be considered in young patients who present with deep vein thrombosis of the femoral and iliac veins. Coagulation abnormalities, frequently found in these patients, may be a contributory factor.

Arched needle technique for inferior alveolar mandibular nerve block.

PubMed

Chakranarayan, Ashish; Mukherjee, B

2013-03-01

One of the most commonly used local anesthetic techniques in dentistry is the Fischer's technique for the inferior alveolar nerve block. Incidentally this technique also suffers the maximum failure rate of approximately 35-45%. We studied a method of inferior alveolar nerve block by injecting a local anesthetic solution into the pterygomandibular space by arching and changing the approach angle of the conventional technique and estimated its efficacy. The needle after the initial insertion is arched and inserted in a manner that it approaches the medial surface of the ramus at an angle almost perpendicular to it. The technique was applied to 100 patients for mandibular molar extraction and the anesthetic effects were assessed. A success rate of 98% was obtained.

The role of left inferior frontal cortex during audiovisual speech perception in infants.

PubMed

Altvater-Mackensen, Nicole; Grossmann, Tobias

2016-06-01

In the first year of life, infants' speech perception attunes to their native language. While the behavioral changes associated with native language attunement are fairly well mapped, the underlying mechanisms and neural processes are still only poorly understood. Using fNIRS and eye tracking, the current study investigated 6-month-old infants' processing of audiovisual speech that contained matching or mismatching auditory and visual speech cues. Our results revealed that infants' speech-sensitive brain responses in inferior frontal brain regions were lateralized to the left hemisphere. Critically, our results further revealed that speech-sensitive left inferior frontal regions showed enhanced responses to matching when compared to mismatching audiovisual speech, and that infants with a preference to look at the speaker's mouth showed an enhanced left inferior frontal response to speech compared to infants with a preference to look at the speaker's eyes. These results suggest that left inferior frontal regions play a crucial role in associating information from different modalities during native language attunement, fostering the formation of multimodal phonological categories. Copyright © 2016 Elsevier Inc. All rights reserved.

A case of atherosclerotic inferior mesenteric artery aneurysm secondary to high flow state.

PubMed

Troisi, Nicola; Esposito, Giovanni; Cefalì, Pietro; Setti, Marco

2011-07-01

Inferior mesenteric artery aneurysms are very rare and they are among the rarest of visceral artery aneurysms. Sometimes, the distribution of the blood flow due to chronic atherosclerotic occlusion of some arteries can establish an increased flow into a particular supplying district (high flow state). A high flow state in a stenotic inferior mesenteric artery in compensation for a mesenteric occlusive disease can produce a rare form of aneurysm. We report the case of an atherosclerotic inferior mesenteric aneurysm secondary to high flow state (association with occlusion of the celiac trunk and severe stenosis of the superior mesenteric artery), treated by open surgical approach. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Response of cat inferior colliculus neurons to binaural beat stimuli: possible mechanisms for sound localization.

PubMed

Kuwada, S; Yin, T C; Wickesberg, R E

1979-11-02

The interaural phase sensitivity of neurons was studied through the use of binaural beat stimuli. The response of most cells was phase-locked to the beat frequency, which provides a possible neural correlate to the human sensation of binaural beats. In addition, this stimulus allowed the direction and rate of interaural phase change to be varied. Some neurons in our sample responded selectively to manipulations of these two variables, which suggests a sensitivity to direction or speed of movement.

The Incidence of Intravascular Needle Entrance during Inferior Alveolar Nerve Block Injection

PubMed Central

Taghavi Zenouz, Ali; Ebrahimi, Hooman; Mahdipour, Masoumeh; Pourshahidi, Sara; Amini, Parisa; Vatankhah, Mahdi

2008-01-01

Background and aims Dentists administer thousands of local anesthetic injections every day. Injection to a highly vascular area such as pterygomandibular space during an inferior alveolar nerve block has a high risk of intravascular needle entrance. Accidental intravascular injection of local anesthetic agent with vasoconstrictor may result in cardiovascular and central nervous system toxicity, as well as tachycardia and hypertension. There are reports that indicate aspiration is not performed in every injection. The aim of the present study was to assess the incidence of intravascular needle entrance in inferior alveolar nerve block injections. Materials and methods Three experienced oral and maxillofacial surgeons performed 359 inferior alveolar nerve block injections using direct or indirect techniques, and reported the results of aspiration. Aspirable syringes and 27 gauge long needles were used, and the method of aspiration was similar in all cases. Data were analyzed using t-test. Results 15.3% of inferior alveolar nerve block injections were aspiration positive. Intravascular needle entrance was seen in 14.2% of cases using direct and 23.3% of cases using indirect block injection techniques. Of all injections, 15.8% were intravascular on the right side and 14.8% were intravascular on the left. There were no statistically significant differences between direct or indirect block injection techniques (P = 0.127) and between right and left injection sites (P = 0.778). Conclusion According to our findings, the incidence of intravascular needle entrance during inferior alveolar nerve block injection was relatively high. It seems that technique and maneuver of injection have no considerable effect in incidence of intravascular needle entrance. PMID:23285329

Inferior alveolar nerve injury after mandibular third molar extraction: a literature review.

PubMed

Sarikov, Rafael; Juodzbalys, Gintaras

2014-01-01

The purpose of this study was to systematically review the comprehensive overview of literature data about injury to the inferior alveolar nerve after lower third molar extraction to discover the prevalence of injury, the risk factors, recovery rates, and alternative methods of treatment. Literature was selected through a search of PubMed electronic databases. Articles from January 2009 to June 2014 were searched. English language articles with a minimum of 6 months patient follow-up and injury analysis by patient's reporting, radiographic, and neurosensory testing were selected. In total, 84 literature sources were reviewed, and 14 of the most relevant articles that are suitable to the criteria were selected. Articles were analyzed on men and women. The influence of lower third molar extraction (especially impacted) on the inferior alveolar nerve was clearly seen. The incidence of injury to the inferior alveolar nerve after lower third molar extraction was about 0.35 - 8.4%. The injury of the inferior alveolar nerve can be predicted by various radiological signs. There are few risk factors that may increase the risk of injury to the nerve such as patients over the age of 24 years old, with horizontal impactions, and extraction by trainee surgeons. Recovery is preferable and permanent injury is very rare.

Transient Delayed Facial Nerve Palsy After Inferior Alveolar Nerve Block Anesthesia

PubMed Central

Tzermpos, Fotios H.; Cocos, Alina; Kleftogiannis, Matthaios; Zarakas, Marissa; Iatrou, Ioannis

2012-01-01

Facial nerve palsy, as a complication of an inferior alveolar nerve block anesthesia, is a rarely reported incident. Based on the time elapsed, from the moment of the injection to the onset of the symptoms, the paralysis could be either immediate or delayed. The purpose of this article is to report a case of delayed facial palsy as a result of inferior alveolar nerve block, which occurred 24 hours after the anesthetic administration and subsided in about 8 weeks. The pathogenesis, treatment, and results of an 8-week follow-up for a 20-year-old patient referred to a private maxillofacial clinic are presented and discussed. The patient's previous medical history was unremarkable. On clinical examination the patient exhibited generalized weakness of the left side of her face with a flat and expressionless appearance, and she was unable to close her left eye. One day before the onset of the symptoms, the patient had visited her dentist for a routine restorative procedure on the lower left first molar and an inferior alveolar block anesthesia was administered. The patient's medical history, clinical appearance, and complete examinations led to the diagnosis of delayed facial nerve palsy. Although neurologic occurrences are rare, dentists should keep in mind that certain dental procedures, such as inferior alveolar block anesthesia, could initiate facial nerve palsy. Attention should be paid during the administration of the anesthetic solution. PMID:22428971

[Investigation of the age-dependent development of brachygnathia inferior in the East Friesian milk sheep].

PubMed

Pielmeier, Ricarda; Kerkmann, Andrea; Distl, Ottmar

2012-01-01

Shortness of the lower jaw (brachygnathia inferior, underbite) is a common anomaly in sheep. In order to study the age-dependent development of brachygnathia inferior, data of 73 East Friesian milk sheep from a breeding experiment over six generations were analysed. Data were recorded in regular intervals of four weeks from birth up to an age of at least 25 weeks. Brachygnathia inferior was determined by the distance between the edge of the central incisor of the lower jaw and the anterior surrounding of the upper jaw (DIFF-UK) using a measuring tape. Four main types of brachygnathia inferior were distinguished using means, standard deviations and maximum values of the individual animals.The thresholds were a maximum and mean DIFF-UK of 0.5 cm and a standard deviation of 0.266 cm. A total of 14 sheep (main types 3 and 4) showed an obvious brachygnathia inferior with mean DIFF-UK larger than 0.5 cm whereof ten animals showed a large variation of DIFF-UK values (standard deviation > 0.226 cm). Mean DIFF-UK values of 59 sheep were smaller than 0.5 cm (main types 1 and 2). One of these 59 animals had during the first four weeks of life DIFF-UK values of 1 cm and than decreasing values reaching zero within the next nine months (main type 2). Five of the 58 animals with main type 1 had a perfect occlusion of jaws, all with DIFF-UK values at zero during the whole recording period. Parents with severe or mild brachygnathia inferior had severely affected progeny. Selection of sheep for breeding with a perfect occlusion of jaws decreases the risk to pass on the hereditary disposition for brachygnathia inferior. An early inspection of potential breeding animals is advisable to detect all cases of brachygnathia inferior even if the underbite decreases in the first year of life.

Diplopia after inferior alveolar nerve block: case report and related physiology.

PubMed

You, Tae Min

2015-06-01

Although inferior alveolar nerve block is one of the most common procedures performed at dental clinics, complications or adverse effects can still occur. On rare occasions, ocular disturbances, such as diplopia, blurred vision, amaurosis, mydriasis, abnormal pupillary light reflex, retrobulbar pain, miosis, and enophthalmos, have also been reported after maxillary and mandibular anesthesia. Generally, these symptoms are temporary but they can be rather distressing to both patients and dental practitioners. Herein, we describe a case of diplopia caused by routine inferior alveolar nerve anesthesia, its related physiology, and management.

Diplopia after inferior alveolar nerve block: case report and related physiology

PubMed Central

2015-01-01

Although inferior alveolar nerve block is one of the most common procedures performed at dental clinics, complications or adverse effects can still occur. On rare occasions, ocular disturbances, such as diplopia, blurred vision, amaurosis, mydriasis, abnormal pupillary light reflex, retrobulbar pain, miosis, and enophthalmos, have also been reported after maxillary and mandibular anesthesia. Generally, these symptoms are temporary but they can be rather distressing to both patients and dental practitioners. Herein, we describe a case of diplopia caused by routine inferior alveolar nerve anesthesia, its related physiology, and management. PMID:28879264

Distractor Evoked Deviations of Saccade Trajectory Are Modulated by Fixation Activity in the Superior Colliculus: Computational and Behavioral Evidence

PubMed Central

Wang, Zhiguo; Theeuwes, Jan

2014-01-01

Previous studies have shown that saccades may deviate towards or away from task irrelevant visual distractors. This observation has been attributed to active suppression (inhibition) of the distractor location unfolding over time: early in time inhibition at the distractor location is incomplete causing deviation towards the distractor, while later in time when inhibition is complete the eyes deviate away from the distractor. In a recent computational study, Wang, Kruijne and Theeuwes proposed an alternative theory that the lateral interactions in the superior colliculus (SC), which are characterized by short-distance excitation and long-distance inhibition, are sufficient for generating both deviations towards and away from distractors. In the present study, we performed a meta-analysis of the literature, ran model simulations and conducted two behavioral experiments to further explore this unconventional theory. Confirming predictions generated by the model simulations, the behavioral experiments show that a) saccades deviate towards close distractors and away from remote distractors, and b) the amount of deviation depends on the strength of fixation activity in the SC, which can be manipulated by turning off the fixation stimulus before or after target onset (Experiment 1), or by varying the eccentricity of the target and distractor (Experiment 2). PMID:25551552

Hepatic venous connection to a persistent inferior caval vein in left isomerism.

PubMed

Guenthard, J; Carvalho, J S; Anderson, R H; Rigby, M L

1990-09-01

In 22 cases of left atrial isomerism studied at the Brompton Hospital, four cases were found to have an unusual arrangement of the abdominal vessels. There was persistence of an inferior caval vein, partially anomalous hepatic venous connection and additional continuation of part of the venous return from the lower body through the azygos venous system. This venous pattern had surgical implications in our index case, since redirection of the inferior caval venous return was necessary.

Spatial transformations between superior colliculus visual and motor response fields during head-unrestrained gaze shifts.

PubMed

Sadeh, Morteza; Sajad, Amirsaman; Wang, Hongying; Yan, Xiaogang; Crawford, John Douglas

2015-12-01

We previously reported that visuomotor activity in the superior colliculus (SC)--a key midbrain structure for the generation of rapid eye movements--preferentially encodes target position relative to the eye (Te) during low-latency head-unrestrained gaze shifts (DeSouza et al., 2011). Here, we trained two monkeys to perform head-unrestrained gaze shifts after a variable post-stimulus delay (400-700 ms), to test whether temporally separated SC visual and motor responses show different spatial codes. Target positions, final gaze positions and various frames of reference (eye, head, and space) were dissociated through natural (untrained) trial-to-trial variations in behaviour. 3D eye and head orientations were recorded, and 2D response field data were fitted against multiple models by use of a statistical method reported previously (Keith et al., 2009). Of 60 neurons, 17 showed a visual response, 12 showed a motor response, and 31 showed both visual and motor responses. The combined visual response field population (n = 48) showed a significant preference for Te, which was also preferred in each visual subpopulation. In contrast, the motor response field population (n = 43) showed a preference for final (relative to initial) gaze position models, and the Te model was statistically eliminated in the motor-only population. There was also a significant shift of coding from the visual to motor response within visuomotor neurons. These data confirm that SC response fields are gaze-centred, and show a target-to-gaze transformation between visual and motor responses. Thus, visuomotor transformations can occur between, and even within, neurons within a single frame of reference and brain structure. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Investigating the role of the superior colliculus in active vision with the visual search paradigm.

PubMed

Shen, Kelly; Valero, Jerome; Day, Gregory S; Paré, Martin

2011-06-01

We review here both the evidence that the functional visuomotor organization of the optic tectum is conserved in the primate superior colliculus (SC) and the evidence for the linking proposition that SC discriminating activity instantiates saccade target selection. We also present new data in response to questions that arose from recent SC visual search studies. First, we observed that SC discriminating activity predicts saccade initiation when monkeys perform an unconstrained search for a target defined by either a single visual feature or a conjunction of two features. Quantitative differences between the results in these two search tasks suggest, however, that SC discriminating activity does not only reflect saccade programming. This finding concurs with visual search studies conducted in posterior parietal cortex and the idea that, during natural active vision, visual attention is shifted concomitantly with saccade programming. Second, the analysis of a large neuronal sample recorded during feature search revealed that visual neurons in the superficial layers do possess discriminating activity. In addition, the hypotheses that there are distinct types of SC neurons in the deeper layers and that they are differently involved in saccade target selection were not substantiated. Third, we found that the discriminating quality of single-neuron activity substantially surpasses the ability of the monkeys to discriminate the target from distracters, raising the possibility that saccade target selection is a noisy process. We discuss these new findings in light of the visual search literature and the view that the SC is a visual salience map for orienting eye movements. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model

PubMed Central

’t Hart, Bert A.; Dunham, Jordon; Faber, Bart W.; Laman, Jon D.; van Horssen, Jack; Bauer, Jan; Kap, Yolanda S.

2017-01-01

The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34–56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund’s adjuvant (IFA)]. Pathological aspects include demyelination of cortical gray matter with microglia activation, oxidative stress, and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant, which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34–56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+ cytotoxic T lymphocytes. PMID:28744286

Prosthetic replacement of the infrahepatic inferior vena cava for leiomyosarcoma.

PubMed

Illuminati, Giulio; Calio', Francesco G; D'Urso, Antonio; Giacobbi, Daniela; Papaspyropoulos, Vassilios; Ceccanei, Gianluca

2006-09-01

Resection of the infrahepatic inferior vena cava associated with prosthetic graft replacement for caval leiomyosarcoma is an acceptable procedure to obtain prolonged and good-quality survival. A consecutive sample clinical study with a mean follow-up of 40 months. The surgical department of an academic tertiary center and an affiliated secondary care center. Eleven patients, with a mean age of 51 years, who have primary leiomyosarcoma of the infrahepatic inferior vena cava. All of the patients underwent radical resection of the tumor en bloc with the affected segment of the vena cava. Reconstruction consisted of 10 cavocaval polytetrafluoroethylene grafts and 1 cavobiliac graft. An associated right nephrectomy was performed in 2 cases. The left renal vein was reimplanted in the graft in 3 cases. Cumulative disease-specific survival, disease-free survival, and graft patency rates expressed by standard life-table analysis. No patients died in the postoperative period. The cumulative (SE) disease-specific survival rate was 53% (21%) at 5 years. The cumulative (SE) disease-free survival rate was 44% (19%) at 5 years. The cumulative (SE) graft patency rate was 67% (22%) at 5 years. Radical resection followed by prosthetic graft reconstruction is a valuable method for treating primary leiomyosarcoma of the infrahepatic inferior vena cava.

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal.

PubMed

Turner, Amy C; Kraev, Igor; Stewart, Michael G; Stramek, Agata; Overton, Paul G; Dommett, Eleanor J

2018-06-04

Heightened distractibility is a core symptom of Attention Deficit Hyperactivity Disorder (ADHD). Effective treatment is normally with chronic orally administered psychostimulants including amphetamine. Treatment prevents worsening of symptoms but the site of therapeutic processes, and their nature, is unknown. Mounting evidence suggests that the superior colliculus (SC) is a key substrate in distractibility and a therapeutic target, so we assessed whether therapeutically-relevant changes are induced in this structure by chronic oral amphetamine. We hypothesized that amphetamine would alter visual responses and morphological measures. Six-week old healthy male rats were treated with oral amphetamine (2, 5 or 10 mg/kg) or a vehicle for one month after which local field potential and multiunit recordings were made from the superficial layers of the SC in response to whole-field light flashes in withdrawal. Rapid Golgi staining was also used to assess dendritic spines, and synaptophysin staining was used to assess synaptic integrity. Chronic amphetamine increased local field potential responses at higher doses, and increased synaptophysin expression, suggesting enhanced visual input involving presynaptic remodelling. No comparable increases in multiunit activity were found suggesting amphetamine suppresses collicular output activity, counterbalancing the increased input. We also report, for the first time, five different dendritic spine types in the superficial layers and show these to be unaffected by amphetamine, indicating that suppression does not involve gross postsynaptic structural alterations. In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD. Copyright © 2018. Published by Elsevier Ltd.

Continuous delivery of ropinirole reverses motor deficits without dyskinesia induction in MPTP-treated common marmosets.

PubMed

Stockwell, K A; Virley, D J; Perren, M; Iravani, M M; Jackson, M J; Rose, S; Jenner, P

2008-05-01

L-DOPA treatment of Parkinson's disease induces a high incidence of motor complications, notably dyskinesia. Longer acting dopamine agonists, e.g. ropinirole, are thought to produce more continuous dopaminergic stimulation and less severe dyskinesia. However, standard oral administration of dopamine agonists does not result in constant plasma drug levels, therefore, more continuous drug delivery may result in both prolonged reversal of motor deficits and reduced levels of dyskinesia. Therefore, we compared the effects of repeated oral administration of ropinirole to constant subcutaneous infusion in MPTP-treated common marmosets. Animals received oral administration (0.4 mg/kg, BID) or continuous infusion of ropinirole (0.8 mg/kg/day) via osmotic minipumps for 14 days (Phase I). The treatments were then switched and continued for a further 14 days (Phase II). In Phase I, locomotor activity was similar between treatment groups but reversal of motor disability was more pronounced in animals receiving continuous infusion. Dyskinesia intensity was low in both groups however there was a trend suggestive of less marked dyskinesia in those animals receiving continuous infusion. In Phase II, increased locomotor activity was maintained but animals switched from oral to continuous treatment showing an initial period of enhanced locomotor activity. The reversal of motor disability was maintained in both groups, however, motor disability tended towards greater improvement following continuous infusion. Importantly, dyskinesia remained low in both groups suggesting that constant delivery of ropinirole neither leads to priming nor expression of dyskinesia. These results suggest that a once-daily controlled-release formulation may provide improvements over existing benefits with standard oral ropinirole in Parkinson's disease patients.