Science.gov

Sample records for auditory signals requires

  1. Efficient visual search from synchronized auditory signals requires transient audiovisual events.

    PubMed

    Van der Burg, Erik; Cass, John; Olivers, Christian N L; Theeuwes, Jan; Alais, David

    2010-05-14

    A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is critical to observe audiovisual integration. Here we demonstrate that temporal coincidence (i.e., synchrony) of auditory and visual components can trigger audiovisual interaction in cluttered displays and consequently produce very fast and efficient target identification. In visual search experiments, subjects found a modulating visual target vastly more efficiently when it was paired with a synchronous auditory signal. By manipulating the kind of temporal modulation (sine wave vs. square wave vs. difference wave; harmonic sine-wave synthesis; gradient of onset/offset ramps) we show that abrupt visual events are required for this search efficiency to occur, and that sinusoidal audiovisual modulations do not support efficient search. Thus, audiovisual temporal alignment will only lead to benefits in visual search if the changes in the component signals are both synchronized and transient. We propose that transient signals are necessary in synchrony-driven binding to avoid spurious interactions with unrelated signals when these occur close together in time.

  2. Efficient Visual Search from Synchronized Auditory Signals Requires Transient Audiovisual Events

    PubMed Central

    Van der Burg, Erik; Cass, John; Olivers, Christian N. L.; Theeuwes, Jan; Alais, David

    2010-01-01

    Background A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is critical to observe audiovisual integration. Methodology/Principal Findings Here we demonstrate that temporal coincidence (i.e., synchrony) of auditory and visual components can trigger audiovisual interaction in cluttered displays and consequently produce very fast and efficient target identification. In visual search experiments, subjects found a modulating visual target vastly more efficiently when it was paired with a synchronous auditory signal. By manipulating the kind of temporal modulation (sine wave vs. square wave vs. difference wave; harmonic sine-wave synthesis; gradient of onset/offset ramps) we show that abrupt visual events are required for this search efficiency to occur, and that sinusoidal audiovisual modulations do not support efficient search. Conclusions/Significance Thus, audiovisual temporal alignment will only lead to benefits in visual search if the changes in the component signals are both synchronized and transient. We propose that transient signals are necessary in synchrony-driven binding to avoid spurious interactions with unrelated signals when these occur close together in time. PMID:20498844

  3. Complex Auditory Signals

    DTIC Science & Technology

    1988-09-01

    Journal of the Acoustical Society of America, 56, 1835-1847. Sachs, M. B., and Young, E.ID. (1979). Encoding of steady-state vowels in the auditory nerve...amplitude to the amplitude of that component of the standard in decibels . If the signal amplitude is one-eighth the amplitude of the com- ponent of the...Isolated pure tone appears to have little to do with how we recognize differences between vowels or broadband consonants. The simplicity of

  4. Attention to natural auditory signals.

    PubMed

    Caporello Bluvas, Emily; Gentner, Timothy Q

    2013-11-01

    The challenge of understanding how the brain processes natural signals is compounded by the fact that such signals are often tied closely to specific natural behaviors and natural environments. This added complexity is especially true for auditory communication signals that can carry information at multiple hierarchical levels, and often occur in the context of other competing communication signals. Selective attention provides a mechanism to focus processing resources on specific components of auditory signals, and simultaneously suppress responses to unwanted signals or noise. Although selective auditory attention has been well-studied behaviorally, very little is known about how selective auditory attention shapes the processing on natural auditory signals, and how the mechanisms of auditory attention are implemented in single neurons or neural circuits. Here we review the role of selective attention in modulating auditory responses to complex natural stimuli in humans. We then suggest how the current understanding can be applied to the study of selective auditory attention in the context natural signal processing at the level of single neurons and populations in animal models amenable to invasive neuroscience techniques. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".

  5. Preferred levels of auditory danger signals.

    PubMed

    Zera, J; Nagórski, A

    2000-01-01

    An important issue at the design stage of the auditory danger signal for a safety system is the signal audibility under various conditions of background noise. The auditory danger signal should be clearly audible but it should not be too loud to avoid fright, startling effects, and nuisance complaints. Criteria for designing auditory danger signals are the subject of the ISO 7731 (International Organization for Standardization [ISO], 1986) international standard and the EN 457 European standard (European Committee for Standardization [CEN], 1992). It is required that the A-weighted sound pressure level of the auditory danger signal is higher in level than the background noise by 15 dB. In this paper, the results of an experiment are reported, in which listeners adjusted most preferred levels of 3 danger signals (tone, sweep, complex sound) in the presence of a noise background (pink noise and industrial noise). The measurements were done for 60-, 70-, 80-, and 90-dB A-weighted levels of noise. Results show that for 60-dB level of noise the most preferred level of the danger signal is 10 to 20 dB above the noise level. However, for 90-dB level of noise, listeners selected a level of the danger signal that was equal to the noise level. Results imply that the criterion in the existing standards is conservative as it requires the level of the danger signal to be higher than the level of noise regardless of the noise level.

  6. Methods for Predicting Job-Ability Requirements: I. Ability Requirements as a Function of Changes in the Characteristics of an Auditory Signal Identification Task.

    ERIC Educational Resources Information Center

    Wheaton, George R.; And Others

    The relationship between variations in an auditory signal identification task and consequent changes in the abilities related to identification performance was investigated. Characteristics of the signal identification task were manipulated by varying signal duration and signal-to-noise ratio. Subjects received a battery of reference ability tests…

  7. Comodulation Enhances Signal Detection via Priming of Auditory Cortical Circuits

    PubMed Central

    Sollini, Joseph

    2016-01-01

    Acoustic environments are composed of complex overlapping sounds that the auditory system is required to segregate into discrete perceptual objects. The functions of distinct auditory processing stations in this challenging task are poorly understood. Here we show a direct role for mouse auditory cortex in detection and segregation of acoustic information. We measured the sensitivity of auditory cortical neurons to brief tones embedded in masking noise. By altering spectrotemporal characteristics of the masker, we reveal that sensitivity to pure tone stimuli is strongly enhanced in coherently modulated broadband noise, corresponding to the psychoacoustic phenomenon comodulation masking release. Improvements in detection were largest following priming periods of noise alone, indicating that cortical segregation is enhanced over time. Transient opsin-mediated silencing of auditory cortex during the priming period almost completely abolished these improvements, suggesting that cortical processing may play a direct and significant role in detection of quiet sounds in noisy environments. SIGNIFICANCE STATEMENT Auditory systems are adept at detecting and segregating competing sound sources, but there is little direct evidence of how this process occurs in the mammalian auditory pathway. We demonstrate that coherent broadband noise enhances signal representation in auditory cortex, and that prolonged exposure to noise is necessary to produce this enhancement. Using optogenetic perturbation to selectively silence auditory cortex during early noise processing, we show that cortical processing plays a crucial role in the segregation of competing sounds. PMID:27927950

  8. Temporal expectation weights visual signals over auditory signals.

    PubMed

    Menceloglu, Melisa; Grabowecky, Marcia; Suzuki, Satoru

    2017-04-01

    Temporal expectation is a process by which people use temporally structured sensory information to explicitly or implicitly predict the onset and/or the duration of future events. Because timing plays a critical role in crossmodal interactions, we investigated how temporal expectation influenced auditory-visual interaction, using an auditory-visual crossmodal congruity effect as a measure of crossmodal interaction. For auditory identification, an incongruent visual stimulus produced stronger interference when the crossmodal stimulus was presented with an expected rather than an unexpected timing. In contrast, for visual identification, an incongruent auditory stimulus produced weaker interference when the crossmodal stimulus was presented with an expected rather than an unexpected timing. The fact that temporal expectation made visual distractors more potent and visual targets less susceptible to auditory interference suggests that temporal expectation increases the perceptual weight of visual signals.

  9. Signal- and Listener- Based Factors in Complex Auditory Pattern Perception

    DTIC Science & Technology

    1994-09-23

    auditory stimuli, or perhaps only on auditory signals from one ear, or only on signals with certain properties (e.g., musical sounds ), etc. To the extent...investigated various aspects of complex auditory perception. These research efforts largely focussed on perception of speech sounds , and provided...research effort made significant progress in clarifying how human listeners decode very .complex sounds . 20. OISTRIUTIONAVAILAILITY OP ABSTRACT 21

  10. Inhibitory Network Interactions Shape the Auditory Processing of Natural Communication Signals in the Songbird Auditory Forebrain

    PubMed Central

    Pinaud, Raphael; Terleph, Thomas A.; Tremere, Liisa A.; Phan, Mimi L.; Dagostin, André A.; Leão, Ricardo M.; Mello, Claudio V.; Vicario, David S.

    2008-01-01

    The role of GABA in the central processing of complex auditory signals is not fully understood. We have studied the involvement of GABAA-mediated inhibition in the processing of birdsong, a learned vocal communication signal requiring intact hearing for its development and maintenance. We focused on caudomedial nidopallium (NCM), an area analogous to parts of the mammalian auditory cortex with selective responses to birdsong. We present evidence that GABAA-mediated inhibition plays a pronounced role in NCM's auditory processing of birdsong. Using immunocytochemistry, we show that approximately half of NCM's neurons are GABAergic. Whole cell patch-clamp recordings in a slice preparation demonstrate that, at rest, spontaneously active GABAergic synapses inhibit excitatory inputs onto NCM neurons via GABAA receptors. Multi-electrode electrophysiological recordings in awake birds show that local blockade of GABAA-mediated inhibition in NCM markedly affects the temporal pattern of song-evoked responses in NCM without modifications in frequency tuning. Surprisingly, this blockade increases the phasic and largely suppresses the tonic response component, reflecting dynamic relationships of inhibitory networks that could include disinhibition. Thus processing of learned natural communication sounds in songbirds, and possibly other vocal learners, may depend on complex interactions of inhibitory networks. PMID:18480371

  11. Auditory display of knee-joint vibration signals

    NASA Astrophysics Data System (ADS)

    Krishnan, Sridhar; Rangayyan, Rangaraj M.; Bell, G. Douglas; Frank, Cyril B.

    2001-12-01

    Sounds generated due to rubbing of knee-joint surfaces may lead to a potential tool for noninvasive assessment of articular cartilage degeneration. In the work reported in the present paper, an attempt is made to perform computer-assisted auscultation of knee joints by auditory display (AD) of vibration signals (also known as vibroarthrographic or VAG signals) emitted during active movement of the leg. Two types of AD methods are considered: audification and sonification. In audification, the VAG signals are scaled in time and frequency using a time-frequency distribution to facilitate aural analysis. In sonification, the instantaneous mean frequency and envelope of the VAG signals are derived and used to synthesize sounds that are expected to facilitate more accurate diagnosis than the original signals by improving their aural quality. Auditory classification experiments were performed by two orthopedic surgeons with 37 VAG signals including 19 normal and 18 abnormal cases. Sensitivity values (correct detection of abnormality) of 31%, 44%, and 83%, and overall classification accuracies of 53%, 40%, and 57% were obtained with the direct playback, audification, and sonification methods, respectively. The corresponding d' scores were estimated to be 1.10, -0.36, and 0.55. The high sensitivity of the sonification method indicates that the technique could lead to improved detection of knee-joint abnormalities; however, additional work is required to improve its specificity and achieve better overall performance.

  12. Interhemispheric support during demanding auditory signal-in-noise processing.

    PubMed

    Stracke, Henning; Okamoto, Hidehiko; Pantev, Christo

    2009-06-01

    We investigated attentional effects on human auditory signal-in-noise processing in a simultaneous masking paradigm using magnetoencephalography. Test signal was a monaural 1000-Hz tone; maskers were binaural band-eliminated noises (BENs) containing stopbands of different widths centered on 1000 Hz. Participants directed attention either to the left or the right ear. In an "irrelevant visual attention" condition subjects focused attention on a screen. Irrespective of attention focus location, the signal appeared randomly either in the left or right ear. During auditory focused attention (left- or right-ear attention), the signal thus randomly appeared either in the attended ("relevant auditory attention" condition) or the nonattended ear ("irrelevant auditory attention" condition). Results showed that N1m source strength was overall increased in the left relative to the right hemisphere, and for right-ear versus left-ear stimulation. Moreover, when attention was focused on the signal ear (relevant auditory attention condition) and the BEN stopbands were narrow, the right-hemispheric N1m source strength was increased, relative to irrelevant auditory attention. Such increments were neither observed in the left hemisphere nor for wide BENs. These novel results indicate 1) left-hemispheric dominance and robustness during auditory signal-in-noise processing, and 2) right-hemispheric assistance during attentive and demanding auditory signal-in-noise processing.

  13. Auditory-Visual Integration in Neonates: A Signal Detection Analysis.

    ERIC Educational Resources Information Center

    Crassini, Boris; Broerse, Jack

    1980-01-01

    The ability of neonates to integrate auditory and visual information into a single percept was investigated using a signal detection methodology. Thirty-two infants ranging in age from 2 to 11 days served as subjects. (Author/MP)

  14. ROTARY PURSUIT TRACKING WITH DIVITENTION TO CUTANEOUS, VISUAL, AND AUDITORY SIGNALS,

    DTIC Science & Technology

    specified signal (light, sound, or electric current) while engaged in tracking. Only one modality was employed at any one time . Three distractive...signal detection tasks were used: (1) simple reaction time (RT), (2) dis junctive RT requiring a spatial discrimination, and (3) disjunctive RT...requiring an intensity discrimination. In all three cases attention to visual signals significantly impaired track ing accuracy. Neither auditory nor cutaneous stimulation disrupted tracking performance. (Author)

  15. Contextual modulation of primary visual cortex by auditory signals

    PubMed Central

    Paton, A. T.

    2017-01-01

    Early visual cortex receives non-feedforward input from lateral and top-down connections (Muckli & Petro 2013 Curr. Opin. Neurobiol. 23, 195–201. (doi:10.1016/j.conb.2013.01.020)), including long-range projections from auditory areas. Early visual cortex can code for high-level auditory information, with neural patterns representing natural sound stimulation (Vetter et al. 2014 Curr. Biol. 24, 1256–1262. (doi:10.1016/j.cub.2014.04.020)). We discuss a number of questions arising from these findings. What is the adaptive function of bimodal representations in visual cortex? What type of information projects from auditory to visual cortex? What are the anatomical constraints of auditory information in V1, for example, periphery versus fovea, superficial versus deep cortical layers? Is there a putative neural mechanism we can infer from human neuroimaging data and recent theoretical accounts of cortex? We also present data showing we can read out high-level auditory information from the activation patterns of early visual cortex even when visual cortex receives simple visual stimulation, suggesting independent channels for visual and auditory signals in V1. We speculate which cellular mechanisms allow V1 to be contextually modulated by auditory input to facilitate perception, cognition and behaviour. Beyond cortical feedback that facilitates perception, we argue that there is also feedback serving counterfactual processing during imagery, dreaming and mind wandering, which is not relevant for immediate perception but for behaviour and cognition over a longer time frame. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044015

  16. Contextual modulation of primary visual cortex by auditory signals.

    PubMed

    Petro, L S; Paton, A T; Muckli, L

    2017-02-19

    Early visual cortex receives non-feedforward input from lateral and top-down connections (Muckli & Petro 2013 Curr. Opin. Neurobiol. 23, 195-201. (doi:10.1016/j.conb.2013.01.020)), including long-range projections from auditory areas. Early visual cortex can code for high-level auditory information, with neural patterns representing natural sound stimulation (Vetter et al. 2014 Curr. Biol. 24, 1256-1262. (doi:10.1016/j.cub.2014.04.020)). We discuss a number of questions arising from these findings. What is the adaptive function of bimodal representations in visual cortex? What type of information projects from auditory to visual cortex? What are the anatomical constraints of auditory information in V1, for example, periphery versus fovea, superficial versus deep cortical layers? Is there a putative neural mechanism we can infer from human neuroimaging data and recent theoretical accounts of cortex? We also present data showing we can read out high-level auditory information from the activation patterns of early visual cortex even when visual cortex receives simple visual stimulation, suggesting independent channels for visual and auditory signals in V1. We speculate which cellular mechanisms allow V1 to be contextually modulated by auditory input to facilitate perception, cognition and behaviour. Beyond cortical feedback that facilitates perception, we argue that there is also feedback serving counterfactual processing during imagery, dreaming and mind wandering, which is not relevant for immediate perception but for behaviour and cognition over a longer time frame.This article is part of the themed issue 'Auditory and visual scene analysis'.

  17. Auditory false perception in schizophrenia: Development and validation of auditory signal detection task.

    PubMed

    Chhabra, Harleen; Sowmya, Selvaraj; Sreeraj, Vanteemar S; Kalmady, Sunil V; Shivakumar, Venkataram; Amaresha, Anekal C; Narayanaswamy, Janardhanan C; Venkatasubramanian, Ganesan

    2016-12-01

    Auditory hallucinations constitute an important symptom component in 70-80% of schizophrenia patients. These hallucinations are proposed to occur due to an imbalance between perceptual expectation and external input, resulting in attachment of meaning to abstract noises; signal detection theory has been proposed to explain these phenomena. In this study, we describe the development of an auditory signal detection task using a carefully chosen set of English words that could be tested successfully in schizophrenia patients coming from varying linguistic, cultural and social backgrounds. Schizophrenia patients with significant auditory hallucinations (N=15) and healthy controls (N=15) performed the auditory signal detection task wherein they were instructed to differentiate between a 5-s burst of plain white noise and voiced-noise. The analysis showed that false alarms (p=0.02), discriminability index (p=0.001) and decision bias (p=0.004) were significantly different between the two groups. There was a significant negative correlation between false alarm rate and decision bias. These findings extend further support for impaired perceptual expectation system in schizophrenia patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Auditory Frequency Sensitivity in the Neonate: A Signal Detection Analysis

    ERIC Educational Resources Information Center

    Weir, C.

    1976-01-01

    Using signal detectability theory, analysis was performed on auditory frequency sensitivity data obtained by Hutt et al, 1968, on human neonates. Reanalysis using 12 male infants confirms superiority of lower frequencies and square waves in provoking startles in neonates. No state of arousal effects were found on sensitivity. (JH)

  19. Auditory trace fear conditioning requires perirhinal cortex

    PubMed Central

    Kholodar-Smith, D.B.; Boguszewski, P.; Brown, T.H.

    2008-01-01

    The hippocampus is well-known to be critical for trace fear conditioning, but nothing is known about the importance of perirhinal cortex (PR), which has reciprocal connections with hippocampus. PR damage severely impairs delay fear conditioning to ultrasonic vocalizations (USVs) and discontinuous tones (pips), but has no effect on delay conditioning to continuous tones (Kholodar-Smith, Allen, and Brown, in press). Here we demonstrate that trace auditory fear conditioning also critically depends on PR function. The trace interval between the CS offset and the US onset was 16 s. Pre-training neurotoxic lesions were produced through multiple injections of N-methyl-D-aspartate along the full length of PR, which was directly visualized during the injections. Control animals received injections with phosphate-buffered saline. Three-dimensional reconstructions of the lesion volumes demonstrated that the neurotoxic damage was well-localized to PR and included most of its anterior-posterior extent. Automated video analysis quantified freezing behavior, which served as the conditional response. PR-damaged rats were profoundly impaired in trace conditioning to either of three different CSs (a USV, tone pips, and a continuous tone) as well as conditioning to the training context. Within both the lesion and control groups, the type of cue had no effect on the mean CR. The overall PR lesion effect size was 2.7 for cue conditioning and 3.9 for context conditioning. We suggest that the role of PR in trace fear conditioning may be distinct from some of its more perceptual functions. The results further define the essential circuitry underlying trace fear conditioning to auditory cues. PMID:18678265

  20. Motor-related signals in the auditory system for listening and learning.

    PubMed

    Schneider, David M; Mooney, Richard

    2015-08-01

    In the auditory system, corollary discharge signals are theorized to facilitate normal hearing and the learning of acoustic behaviors, including speech and music. Despite clear evidence of corollary discharge signals in the auditory cortex and their presumed importance for hearing and auditory-guided motor learning, the circuitry and function of corollary discharge signals in the auditory cortex are not well described. In this review, we focus on recent developments in the mouse and songbird that provide insights into the circuitry that transmits corollary discharge signals to the auditory system and the function of these signals in the context of hearing and vocal learning.

  1. Auditory signal processing in communication: perception and performance of vocal sounds.

    PubMed

    Prather, Jonathan F

    2013-11-01

    Learning and maintaining the sounds we use in vocal communication require accurate perception of the sounds we hear performed by others and feedback-dependent imitation of those sounds to produce our own vocalizations. Understanding how the central nervous system integrates auditory and vocal-motor information to enable communication is a fundamental goal of systems neuroscience, and insights into the mechanisms of those processes will profoundly enhance clinical therapies for communication disorders. Gaining the high-resolution insight necessary to define the circuits and cellular mechanisms underlying human vocal communication is presently impractical. Songbirds are the best animal model of human speech, and this review highlights recent insights into the neural basis of auditory perception and feedback-dependent imitation in those animals. Neural correlates of song perception are present in auditory areas, and those correlates are preserved in the auditory responses of downstream neurons that are also active when the bird sings. Initial tests indicate that singing-related activity in those downstream neurons is associated with vocal-motor performance as opposed to the bird simply hearing itself sing. Therefore, action potentials related to auditory perception and action potentials related to vocal performance are co-localized in individual neurons. Conceptual models of song learning involve comparison of vocal commands and the associated auditory feedback to compute an error signal that is used to guide refinement of subsequent song performances, yet the sites of that comparison remain unknown. Convergence of sensory and motor activity onto individual neurons points to a possible mechanism through which auditory and vocal-motor signals may be linked to enable learning and maintenance of the sounds used in vocal communication. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives". Copyright © 2013

  2. Auditory Signal Processing in Communication: Perception and Performance of Vocal Sounds

    PubMed Central

    Prather, Jonathan F.

    2013-01-01

    Learning and maintaining the sounds we use in vocal communication require accurate perception of the sounds we hear performed by others and feedback-dependent imitation of those sounds to produce our own vocalizations. Understanding how the central nervous system integrates auditory and vocal-motor information to enable communication is a fundamental goal of systems neuroscience, and insights into the mechanisms of those processes will profoundly enhance clinical therapies for communication disorders. Gaining the high-resolution insight necessary to define the circuits and cellular mechanisms underlying human vocal communication is presently impractical. Songbirds are the best animal model of human speech, and this review highlights recent insights into the neural basis of auditory perception and feedback-dependent imitation in those animals. Neural correlates of song perception are present in auditory areas, and those correlates are preserved in the auditory responses of downstream neurons that are also active when the bird sings. Initial tests indicate that singing-related activity in those downstream neurons is associated with vocal-motor performance as opposed to the bird simply hearing itself sing. Therefore, action potentials related to auditory perception and action potentials related to vocal performance are co-localized in individual neurons. Conceptual models of song learning involve comparison of vocal commands and the associated auditory feedback to compute an error signal that is used to guide refinement of subsequent song performances, yet the sites of that comparison remain unknown. Convergence of sensory and motor activity onto individual neurons points to a possible mechanism through which auditory and vocal-motor signals may be linked to enable learning and maintenance of the sounds used in vocal communication. PMID:23827717

  3. Differential auditory signal processing in an animal model

    NASA Astrophysics Data System (ADS)

    Lim, Dukhwan; Kim, Chongsun; Chang, Sun O.

    2002-05-01

    Auditory evoked responses were collected in male zebra finches (Poephila guttata) to objectively determine differential frequency selectivity. First, the mating call of the animal was recorded and analyzed for its frequency components through the customized program. Then, auditory brainstem responses and cortical responses of each anesthetized animal were routinely recorded in response to tone bursts of 1-8 kHz derived from the corresponding mating call spectrum. From the results, most mating calls showed relatively consistent spectral structures. The upper limit of the spectrum was well under 10 kHz. The peak energy bands were concentrated in the region less than 5 kHz. The assessment of auditory brainstem responses and cortical evoked potentials showed differential selectivity with a series of characteristic scales. This system appears to be an excellent model to investigate complex sound processing and related language behaviors. These data could also be used in designing effective signal processing strategies in auditory rehabilitation devices such as hearing aids and cochlear implants. [Work supported by Brain Science & Engineering Program from Korean Ministry of Science and Technology.

  4. Hearing conspecific vocal signals alters peripheral auditory sensitivity

    PubMed Central

    Gall, Megan D.; Wilczynski, Walter

    2015-01-01

    We investigated whether hearing advertisement calls over several nights, as happens in natural frog choruses, modified the responses of the peripheral auditory system in the green treefrog, Hyla cinerea. Using auditory evoked potentials (AEP), we found that exposure to 10 nights of a simulated male chorus lowered auditory thresholds in males and females, while exposure to random tones had no effect in males, but did result in lower thresholds in females. The threshold change was larger at the lower frequencies stimulating the amphibian papilla than at higher frequencies stimulating the basilar papilla. Suprathreshold responses to tonal stimuli were assessed for two peaks in the AEP recordings. For the peak P1 (assessed for 0.8–1.25 kHz), peak amplitude increased following chorus exposure. For peak P2 (assessed for 2–4 kHz), peak amplitude decreased at frequencies between 2.5 and 4.0 kHz, but remained unaltered at 2.0 kHz. Our results show for the first time, to our knowledge, that hearing dynamic social stimuli, like frog choruses, can alter the responses of the auditory periphery in a way that could enhance the detection of and response to conspecific acoustic communication signals. PMID:25972471

  5. A basic study on universal design of auditory signals in automobiles.

    PubMed

    Yamauchi, Katsuya; Choi, Jong-dae; Maiguma, Ryo; Takada, Masayuki; Iwamiya, Shin-ichiro

    2004-11-01

    In this paper, the impression of various kinds of auditory signals currently used in automobiles and a comprehensive evaluation were measured by a semantic differential method. The desirable acoustic characteristic was examined for each type of auditory signal. Sharp sounds with dominant high-frequency components were not suitable for auditory signals in automobiles. This trend is expedient for the aged whose auditory sensitivity in the high frequency region is lower. When intermittent sounds were used, a longer OFF time was suitable. Generally, "dull (not sharp)" and "calm" sounds were appropriate for auditory signals. Furthermore, the comparison between the frequency spectrum of interior noise in automobiles and that of suitable sounds for various auditory signals indicates that the suitable sounds are not easily masked. The suitable auditory signals for various purposes is a good solution from the viewpoint of universal design.

  6. A Binaural Neuromorphic Auditory Sensor for FPGA: A Spike Signal Processing Approach.

    PubMed

    Jimenez-Fernandez, Angel; Cerezuela-Escudero, Elena; Miro-Amarante, Lourdes; Dominguez-Moralse, Manuel Jesus; de Asis Gomez-Rodriguez, Francisco; Linares-Barranco, Alejandro; Jimenez-Moreno, Gabriel

    2017-04-01

    This paper presents a new architecture, design flow, and field-programmable gate array (FPGA) implementation analysis of a neuromorphic binaural auditory sensor, designed completely in the spike domain. Unlike digital cochleae that decompose audio signals using classical digital signal processing techniques, the model presented in this paper processes information directly encoded as spikes using pulse frequency modulation and provides a set of frequency-decomposed audio information using an address-event representation interface. In this case, a systematic approach to design led to a generic process for building, tuning, and implementing audio frequency decomposers with different features, facilitating synthesis with custom features. This allows researchers to implement their own parameterized neuromorphic auditory systems in a low-cost FPGA in order to study the audio processing and learning activity that takes place in the brain. In this paper, we present a 64-channel binaural neuromorphic auditory system implemented in a Virtex-5 FPGA using a commercial development board. The system was excited with a diverse set of audio signals in order to analyze its response and characterize its features. The neuromorphic auditory system response times and frequencies are reported. The experimental results of the proposed system implementation with 64-channel stereo are: a frequency range between 9.6 Hz and 14.6 kHz (adjustable), a maximum output event rate of 2.19 Mevents/s, a power consumption of 29.7 mW, the slices requirements of 11141, and a system clock frequency of 27 MHz.

  7. The effect of psychological stress and expectation on auditory perception: A signal detection analysis.

    PubMed

    Hoskin, Robert; Hunter, Mike D; Woodruff, Peter W R

    2014-11-01

    Both psychological stress and predictive signals relating to expected sensory input are believed to influence perception, an influence which, when disrupted, may contribute to the generation of auditory hallucinations. The effect of stress and semantic expectation on auditory perception was therefore examined in healthy participants using an auditory signal detection task requiring the detection of speech from within white noise. Trait anxiety was found to predict the extent to which stress influenced response bias, resulting in more anxious participants adopting a more liberal criterion, and therefore experiencing more false positives, when under stress. While semantic expectation was found to increase sensitivity, its presence also generated a shift in response bias towards reporting a signal, suggesting that the erroneous perception of speech became more likely. These findings provide a potential cognitive mechanism that may explain the impact of stress on hallucination-proneness, by suggesting that stress has the tendency to alter response bias in highly anxious individuals. These results also provide support for the idea that top-down processes such as those relating to semantic expectation may contribute to the generation of auditory hallucinations.

  8. Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia.

    PubMed

    Kuga, Hironori; Onitsuka, Toshiaki; Hirano, Yoji; Nakamura, Itta; Oribe, Naoya; Mizuhara, Hiroaki; Kanai, Ryota; Kanba, Shigenobu; Ueno, Takefumi

    2016-10-01

    Recent MRI studies have shown that schizophrenia is characterized by reductions in brain gray matter, which progress in the acute state of the disease. Cortical circuitry abnormalities in gamma oscillations, such as deficits in the auditory steady state response (ASSR) to gamma frequency (>30-Hz) stimulation, have also been reported in schizophrenia patients. In the current study, we investigated neural responses during click stimulation by BOLD signals. We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ), 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ), and 24 healthy controls (HC), assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

  9. Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

    DOE PAGES

    Blundon, Jay A.; Roy, Noah C.; Teubner, Brett J. W.; ...

    2017-06-30

    Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. We show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5'-nucleotidase–dependent adenosine production or A1–adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement ofmore » tone-discrimination abilities. We determined that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.« less

  10. Signal analysis of auditory evoked cortical fields in fetal magnetoencephalography.

    PubMed

    Schneider, U; Schleussner, E; Haueisen, J; Nowak, H; Seewald, H J

    2001-01-01

    Magnetoencephalography (MEG) using auditory evoked cortical fields (AEF) is an absolutely non-invasive method of passive measurement which utilizes magnetic fields caused by specific cortical activity. By applying the exceptionally sensitive SQUID technology to record these fields of dipolar configuration produced by the fetal brain, MEG as an investigational tool could provide new insights into the development of the human brain in utero. The major constraint to this application is a very low signal-to-noise ratio (SNR) that has to be attributed to a variety of factors including the magnetic signals generated by the fetal and maternal hearts which inevitably obscure a straightforward signal analysis. By applying a new algorithm of specific heart artefact reduction based on the relative regularity of the heart signals, we were able to increase the chance of extracting a fetal AEF from the raw data by the means of averaging techniques and principle component analysis. Results from 27 pregnant, healthy women (third trimester of their uncomplicated pregnancy) indicate an improved detection rate and the reproducibility of the fetal MEG. We evaluate and discuss a-priori criteria for signal analyses which will enable us to systematically analyze additional limiting factors, to further enhance the efficiency of this method and to promote the assessment of its possible clinical value in the future.

  11. Sustained Attention in Auditory and Visual Monitoring Tasks: Evaluation of the Administration of a Rest Break or Exogenous Vibrotactile Signals.

    PubMed

    Arrabito, G Robert; Ho, Geoffrey; Aghaei, Behzad; Burns, Catherine; Hou, Ming

    2015-12-01

    Performance and mental workload were observed for the administration of a rest break or exogenous vibrotactile signals in auditory and visual monitoring tasks. Sustained attention is mentally demanding. Techniques are required to improve observer performance in vigilance tasks. Participants (N = 150) monitored an auditory or a visual display for changes in signal duration in a 40-min watch. During the watch, participants were administered a rest break or exogenous vibrotactile signals. Detection accuracy was significantly greater in the auditory than in the visual modality. A short rest break restored detection accuracy in both sensory modalities following deterioration in performance. Participants experienced significantly lower mental workload when monitoring auditory than visual signals, and a rest break significantly reduced mental workload in both sensory modalities. Exogenous vibrotactile signals had no beneficial effects on performance, or mental workload. A rest break can restore performance in auditory and visual vigilance tasks. Although sensory differences in vigilance tasks have been studied, this study is the initial effort to investigate the effects of a rest break countermeasure in both auditory and visual vigilance tasks, and it is also the initial effort to explore the effects of the intervention of a rest break on the perceived mental workload of auditory and visual vigilance tasks. Further research is warranted to determine exact characteristics of effective exogenous vibrotactile signals in vigilance tasks. Potential applications of this research include procedures for decreasing the temporal decline in observer performance and the high mental workload imposed by vigilance tasks. © 2015, Her Majesty the Queen in Right of Canada, as represented by the Minister of National Defence.

  12. A transient auditory signal shifts the perceived offset position of a moving visual object.

    PubMed

    Chien, Sung-En; Ono, Fuminori; Watanabe, Katsumi

    2013-01-01

    Information received from different sensory modalities profoundly influences human perception. For example, changes in the auditory flutter rate induce changes in the apparent flicker rate of a flashing light (Shipley, 1964). In the present study, we investigated whether auditory information would affect the perceived offset position of a moving object. In Experiment 1, a visual object moved toward the center of the computer screen and disappeared abruptly. A transient auditory signal was presented at different times relative to the moment when the object disappeared. The results showed that if the auditory signal was presented before the abrupt offset of the moving object, the perceived final position was shifted backward, implying that the perceived visual offset position was affected by the transient auditory information. In Experiment 2, we presented the transient auditory signal to either the left or the right ear. The results showed that the perceived visual offset shifted backward more strongly when the auditory signal was presented to the same side from which the moving object originated. In Experiment 3, we found that the perceived timing of the visual offset was not affected by the spatial relation between the auditory signal and the visual offset. The present results are interpreted as indicating that an auditory signal may influence the offset position of a moving object through both spatial and temporal processes.

  13. Temporally selective processing of communication signals by auditory midbrain neurons

    PubMed Central

    Christensen-Dalsgaard, Jakob; Kelley, Darcy B.

    2011-01-01

    Perception of the temporal structure of acoustic signals contributes critically to vocal signaling. In the aquatic clawed frog Xenopus laevis, calls differ primarily in the temporal parameter of click rate, which conveys sexual identity and reproductive state. We show here that an ensemble of auditory neurons in the laminar nucleus of the torus semicircularis (TS) of X. laevis specializes in encoding vocalization click rates. We recorded single TS units while pure tones, natural calls, and synthetic clicks were presented directly to the tympanum via a vibration-stimulation probe. Synthesized click rates ranged from 4 to 50 Hz, the rate at which the clicks begin to overlap. Frequency selectivity and temporal processing were characterized using response-intensity curves, temporal-discharge patterns, and autocorrelations of reduplicated responses to click trains. Characteristic frequencies ranged from 140 to 3,250 Hz, with minimum thresholds of −90 dB re 1 mm/s at 500 Hz and −76 dB at 1,100 Hz near the dominant frequency of female clicks. Unlike units in the auditory nerve and dorsal medullary nucleus, most toral units respond selectively to the behaviorally relevant temporal feature of the rate of clicks in calls. The majority of neurons (85%) were selective for click rates, and this selectivity remained unchanged over sound levels 10 to 20 dB above threshold. Selective neurons give phasic, tonic, or adapting responses to tone bursts and click trains. Some algorithms that could compute temporally selective receptive fields are described. PMID:21289132

  14. Smoke alarms for sleeping adults who are hard-of-hearing: comparison of auditory, visual, and tactile signals.

    PubMed

    Bruck, Dorothy; Thomas, Ian R

    2009-02-01

    People who are hard-of-hearing may rely on auditory, visual, or tactile alarms in a fire emergency, and US standards require strobe lights in hotel bedrooms to provide emergency notification for people with hearing loss. This is the first study to compare the waking effectiveness of a variety of auditory (beeps), tactile (bed and pillow shakers), and visual (strobe lights) signals at a range of intensities. Three auditory signals, a bed shaker, a pillow shaker, and strobe lights were presented to 38 adults (aged 18 to 80 yr) with mild to moderately severe hearing loss of 25 to 70 dB (in both ears), during slow-wave sleep (deep sleep). Two of the auditory signals were selected on the basis that they had the lowest auditory thresholds when awake (from a range of eight signals). The third auditory signal was the current 3100-Hz smoke alarm. All auditory signals were tested below, at, and above the decibel level prescribed by the applicable standard for bedrooms (75 dBA). In the case of bed and pillow shakers intensities below, at, and above the level as purchased were tested. For strobe lights three levels were used, all of which were above the applicable standard. The intensity level at which participants awoke was identified by electroencephalograph monitoring. The most effective signal was a 520-Hz square wave auditory signal, waking 92% at 75 dBA, compared with 56% waking to the 75 dBA high-pitched alarm. Bed and pillow shakers awoke 80 to 84% at the intensity level as purchased. The strobe lights awoke only 27% at an intensity above the US standard. Nonparametric analyses confirmed that the 520-Hz square wave signal was significantly more effective than the current smoke alarm and the strobe lights in waking this population. A low-frequency square wave signal has now been found to be significantly more effective than all tested alternatives in a number of populations (hard-of-hearing, children, older adults, young adults, alcohol impaired) and should be adopted

  15. Sound Sequence Discrimination Learning Motivated by Reward Requires Dopaminergic D2 Receptor Activation in the Rat Auditory Cortex

    ERIC Educational Resources Information Center

    Kudoh, Masaharu; Shibuki, Katsuei

    2006-01-01

    We have previously reported that sound sequence discrimination learning requires cholinergic inputs to the auditory cortex (AC) in rats. In that study, reward was used for motivating discrimination behavior in rats. Therefore, dopaminergic inputs mediating reward signals may have an important role in the learning. We tested the possibility in the…

  16. Sound Sequence Discrimination Learning Motivated by Reward Requires Dopaminergic D2 Receptor Activation in the Rat Auditory Cortex

    ERIC Educational Resources Information Center

    Kudoh, Masaharu; Shibuki, Katsuei

    2006-01-01

    We have previously reported that sound sequence discrimination learning requires cholinergic inputs to the auditory cortex (AC) in rats. In that study, reward was used for motivating discrimination behavior in rats. Therefore, dopaminergic inputs mediating reward signals may have an important role in the learning. We tested the possibility in the…

  17. A hardware model of the auditory periphery to transduce acoustic signals into neural activity

    PubMed Central

    Tateno, Takashi; Nishikawa, Jun; Tsuchioka, Nobuyoshi; Shintaku, Hirofumi; Kawano, Satoyuki

    2013-01-01

    To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number. PMID:24324432

  18. Effects of age, signal level, and signal rate on the auditory middle latency response.

    PubMed

    Tucker, D A; Ruth, R A

    1996-04-01

    The effects of age, signal rate, and signal level on the maturing auditory middle latency response (AMLR) were evaluated in 50 normal-hearing subjects ranging in age from 2 days to 35 years. Ipsilateral and contralateral AMLR waveforms were recorded in newborns (n = 10), children (n = 10), preteens (n = 10), teens (n = 10), and adults (n = 10). The AMLR Pa waveform was obtained in 70 to 100 percent of all subjects. The variables of age, signal level, and site of recording significantly affected Pa peak amplitude and absolute latency. However, stimulus rate did not significantly affect the response.

  19. Requirement of the auditory association cortex for discrimination of vowel-like sounds in rats.

    PubMed

    Kudoh, Masaharu; Nakayama, Yoko; Hishida, Ryuichi; Shibuki, Katsuei

    2006-11-27

    We investigated the roles of the auditory cortex in discrimination learning of vowel-like sounds consisting of multiple formants. Rats were trained to discriminate between synthetic sounds with four formants. Bilateral electrolytic lesions including the primary auditory cortex and the dorsal auditory association cortex impaired multiformant discrimination, whereas they did not significantly affect discrimination between sounds with a single formant or between pure tones. Local lesions restricted to the dorsal/rostral auditory association cortex were sufficient to attenuate multiformant discrimination learning, and lesions restricted to the primary auditory cortex had no significant effects. These findings indicate that the dorsal/rostral auditory association cortex but not the primary auditory cortex is required for discrimination learning of vowel-like sounds with multiple formants in rats.

  20. Sounds and beyond: multisensory and other non-auditory signals in the inferior colliculus

    PubMed Central

    Gruters, Kurtis G.; Groh, Jennifer M.

    2012-01-01

    The inferior colliculus (IC) is a major processing center situated mid-way along both the ascending and descending auditory pathways of the brain stem. Although it is fundamentally an auditory area, the IC also receives anatomical input from non-auditory sources. Neurophysiological studies corroborate that non-auditory stimuli can modulate auditory processing in the IC and even elicit responses independent of coincident auditory stimulation. In this article, we review anatomical and physiological evidence for multisensory and other non-auditory processing in the IC. Specifically, the contributions of signals related to vision, eye movements and position, somatosensation, and behavioral context to neural activity in the IC will be described. These signals are potentially important for localizing sound sources, attending to salient stimuli, distinguishing environmental from self-generated sounds, and perceiving and generating communication sounds. They suggest that the IC should be thought of as a node in a highly interconnected sensory, motor, and cognitive network dedicated to synthesizing a higher-order auditory percept rather than simply reporting patterns of air pressure detected by the cochlea. We highlight some of the potential pitfalls that can arise from experimental manipulations that may disrupt the normal function of this network, such as the use of anesthesia or the severing of connections from cortical structures that project to the IC. Finally, we note that the presence of these signals in the IC has implications for our understanding not just of the IC but also of the multitude of other regions within and beyond the auditory system that are dependent on signals that pass through the IC. Whatever the IC “hears” would seem to be passed both “upward” to thalamus and thence to auditory cortex and beyond, as well as “downward” via centrifugal connections to earlier areas of the auditory pathway such as the cochlear nucleus. PMID:23248584

  1. Cardiac Change of Retarded and Nonretarded Infants to an Auditory Signal.

    ERIC Educational Resources Information Center

    Bradley-Johnson, Sharon; Travers, Robert M. W.

    1979-01-01

    To examine individual differences in conditions accompanying attention, the cardiac change of ten normal and retarded infants was measured in response to an auditory signal over 15 trials. (Author/DLS)

  2. Instantaneous and Frequency-Warped Signal Processing Techniques for Auditory Source Separation.

    NASA Astrophysics Data System (ADS)

    Wang, Avery Li-Chun

    which require a small fraction of the computational power of conventional FIR implementations. This design strategy is based on truncated and stabilized IIR filters. These signal-processing methods have been applied to the problem of auditory source separation, resulting in voice separation from complex music that is significantly better than previous results at far lower computational cost.

  3. The effect of auditory verbal imagery on signal detection in hallucination-prone individuals

    PubMed Central

    Moseley, Peter; Smailes, David; Ellison, Amanda; Fernyhough, Charles

    2016-01-01

    Cognitive models have suggested that auditory hallucinations occur when internal mental events, such as inner speech or auditory verbal imagery (AVI), are misattributed to an external source. This has been supported by numerous studies indicating that individuals who experience hallucinations tend to perform in a biased manner on tasks that require them to distinguish self-generated from non-self-generated perceptions. However, these tasks have typically been of limited relevance to inner speech models of hallucinations, because they have not manipulated the AVI that participants used during the task. Here, a new paradigm was employed to investigate the interaction between imagery and perception, in which a healthy, non-clinical sample of participants were instructed to use AVI whilst completing an auditory signal detection task. It was hypothesized that AVI-usage would cause participants to perform in a biased manner, therefore falsely detecting more voices in bursts of noise. In Experiment 1, when cued to generate AVI, highly hallucination-prone participants showed a lower response bias than when performing a standard signal detection task, being more willing to report the presence of a voice in the noise. Participants not prone to hallucinations performed no differently between the two conditions. In Experiment 2, participants were not specifically instructed to use AVI, but retrospectively reported how often they engaged in AVI during the task. Highly hallucination-prone participants who retrospectively reported using imagery showed a lower response bias than did participants with lower proneness who also reported using AVI. Results are discussed in relation to prominent inner speech models of hallucinations. PMID:26435050

  4. Directivity of hearing of auditory danger signal emitted by overhead crane.

    PubMed

    Młyński, Rafał; Kozłowski, Emil

    The objective of the research has been to provide an answer to the question of what the possibilities of determining the direction of approach of the auditory danger signal emitted by an overhead crane appropriately are. Cases of use and no use of earmuffs (in the passive mode and level-dependent ones) were all taken into consideration. The auditory danger signal and ambient noise were recorded in an industrial hall. Signals were reproduced at an experimental set-up, using a large number of speakers. Eight speakers for reproduction of the auditory danger signal were placed above a subject's head. The study participants would indicate the direction from which, according to them, the auditory danger signal was being emitted. The average percentage rate of the correct localization amounted to 75.8% when the overhead crane's signal wasn't masked. The presence of ambient noise caused a reduction of the number of correctly identified localization to 66.6%. The use of earmuffs in the passive mode resulted in the worst results (44.5%). There is some improvement when level-dependent earmuffs are used (57.3%). In situations where it is important to identify the direction from which the auditory danger signal generated by the crane's signaling device is approaching, it is beneficial to use level-dependent earmuffs rather than earmuffs in the passive mode. Correct identification of whether the auditory danger signal generated by the crane's signaling device is approaching from the left or right side is almost perfect, however correct identification of whether the signal is approaching from the front or back of a person is not always possible. Med Pr 2016;67(5):589-597.

  5. Pip and Pop: Nonspatial Auditory Signals Improve Spatial Visual Search

    ERIC Educational Resources Information Center

    Van der Burg, Erik; Olivers, Christian N. L.; Bronkhorst, Adelbert W.; Theeuwes, Jan

    2008-01-01

    Searching for an object within a cluttered, continuously changing environment can be a very time-consuming process. The authors show that a simple auditory pip drastically decreases search times for a synchronized visual object that is normally very difficult to find. This effect occurs even though the pip contains no information on the location…

  6. Effects of auditory noise on the psychophysical detection of visual signals: cross-modal stochastic resonance.

    PubMed

    Manjarrez, Elias; Mendez, Ignacio; Martinez, Lourdes; Flores, Amira; Mirasso, Claudio R

    2007-03-30

    Harper [D.W. Harper, Signal detection analysis of effect of white noise intensity on sensitivity to visual flicker, Percept. Mot. Skills 48 (1979) 791-798] demonstrated that the visual flicker sensitivity was an inverted U-like function of the intensity of different levels of auditory noise from 50 to 90dB (SPL), without concomitant changes in the response bias. The aim of the present study was to extend these observations in the context of the stochastic resonance, a counterintuitive phenomenon in which a particular level of noise enhances the response of a nonlinear system to a weak input signal. We show psychophysical evidence in a yes-no paradigm for the existence of a stochastic resonance-like phenomenon in the auditory-visual interactions. We show that the detection of a weak visual signal was an inverted U-like function of the intensity of different levels of auditory noise. Nevertheless, for a strong visual signal the auditory noise acts in detriment of the ability of visual detection. Our results suggest that auditory noise could be employed in vision rehabilitation interventions in order to improve the detection of weak visual signals.

  7. Auditory Warnings, Signal-Referent Relations, and Natural Indicators: Re-Thinking Theory and Application

    ERIC Educational Resources Information Center

    Petocz, Agnes; Keller, Peter E.; Stevens, Catherine J.

    2008-01-01

    In auditory warning design the idea of the strength of the association between sound and referent has been pivotal. Research has proceeded via constructing classification systems of signal-referent associations and then testing predictions about ease of learning of different levels of signal-referent relation strength across and within different…

  8. Presenting multiple auditory signals using multiple sound cards in Visual Basic 6.0.

    PubMed

    Chan, Jason S; Spence, Charles

    2003-02-01

    In auditory research, it is often desirable to present more than two auditory stimuli at any one time. Although the technology has been available for some time, the majority of researchers have not utilized it. This article provides a simple means of presenting multiple, concurrent, independent auditory events, using two or more different sound cards installed within a single computer. By enabling the presentation of more auditory events, we can hope to gain a better understanding of the cognitive and attentional processes operating under more complex and realistic scenes, such as that embodied by the cocktail party effect. The software requirements are Windows 98SR2/Me/NT4/2000/XP, Visual Basic 6.0, and DirectX 7.0 or above. The hardware requirements are a Pentium II, 128 MB RAM, and two or more different sound cards.

  9. Auditory neglect.

    PubMed Central

    De Renzi, E; Gentilini, M; Barbieri, C

    1989-01-01

    Auditory neglect was investigated in normal controls and in patients with a recent unilateral hemispheric lesion, by requiring them to detect the interruptions that occurred in one ear in a sound delivered through earphones either mono-aurally or binaurally. Control patients accurately detected interruptions. One left brain damaged (LBD) patient missed only once in the ipsilateral ear while seven of the 30 right brain damaged (RBD) patients missed more than one signal in the monoaural test and nine patients did the same in the binaural test. Omissions were always more marked in the left ear and in the binaural test with a significant ear by test interaction. The lesion of these patients was in the parietal lobe (five patients) and the thalamus (four patients). The relation of auditory neglect to auditory extinction was investigated and found to be equivocal, in that there were seven RBD patients who showed extinction, but not neglect and, more importantly, two patients who exhibited the opposite pattern, thus challenging the view that extinction is a minor form of neglect. Also visual and auditory neglect were not consistently correlated, the former being present in nine RBD patients without auditory neglect and the latter in two RBD patients without visual neglect. The finding that in some RBD patients with auditory neglect omissions also occurred, though with less frequency, in the right ear, points to a right hemisphere participation in the deployment of attention not only to the contralateral, but also to the ipsilateral space. PMID:2732732

  10. The influence of signal type on the internal auditory representation of a room

    NASA Astrophysics Data System (ADS)

    Teret, Elizabeth

    Currently, architectural acousticians make no real distinction between a room impulse response and the auditory system's internal representation of a room. With this lack of a good model for the auditory representation of a room, it is indirectly assumed that our internal representation of a room is independent of the sound source needed to make the room characteristics audible. The extent to which this assumption holds true is examined with perceptual tests. Listeners are presented with various pairs of signals (music, speech, and noise) convolved with synthesized impulse responses of different reverberation times. They are asked to adjust the reverberation of one of the signals to match the other. Analysis of the data show that the source signal significantly influences perceived reverberance. Listeners are less accurate when matching reverberation times of varied signals than they are with identical signals. Additional testing shows that perception of reverberation can be linked to the existence of transients in the signal.

  11. Psychophysical evaluation of auditory signals in passenger vehicles.

    PubMed

    Chi, Chia-Fen; Dewi, Ratna Sari; Huang, Min-Hua

    2017-03-01

    Twenty-one experienced drivers were recruited for the evaluation of sounds of four functions (horn, indicator, door open warning, and parking sensor) made by 11 car brand names. Each participant was required to evaluate all of the above sound signals by a pair-comparison test. After the comparison test, each participant was shown his/her pair-comparison result and was asked to comment on their preference and appropriateness of a sound. The physical properties and interview data were compared and summarized to propose design recommendations. Our results indicate that complex tones and a fundamental frequency between 500 and 1000 Hz were most preferred for horns while for indicators the preferred sounds had a higher dominant frequency. To reduce monotony, the indicators with double clicks and an OFF time interval of between 330 and 400 ms between two clicks were most preferred. Regarding door warning sounds, the waveform starting with a higher intensity then fading towards zero intensity is most preferred while for parking sensors, sounds beginning with a longer OFF time (about 500 ms) and having 3 or 4 distinctive tempo variations were most preferred. The relationship between pleasurability and pitch, loudness, and the tempo of sound signals basically followed an inverted-U function. Sound designers should avoid using very extreme parameter values when generating sound for a given function. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. A psychophysiological evaluation of the perceived urgency of auditory warning signals

    NASA Technical Reports Server (NTRS)

    Burt, J. L.; Bartolome, D. S.; Burdette, D. W.; Comstock, J. R. Jr

    1995-01-01

    One significant concern that pilots have about cockpit auditory warnings is that the signals presently used lack a sense of priority. The relationship between auditory warning sound parameters and perceived urgency is, therefore, an important topic of enquiry in aviation psychology. The present investigation examined the relationship among subjective assessments of urgency, reaction time, and brainwave activity with three auditory warning signals. Subjects performed a tracking task involving automated and manual conditions, and were presented with auditory warnings having various levels of perceived and situational urgency. Subjective assessments revealed that subjects were able to rank warnings on an urgency scale, but rankings were altered after warnings were mapped to a situational urgency scale. Reaction times differed between automated and manual tracking task conditions, and physiological data showed attentional differences in response to perceived and situational warning urgency levels. This study shows that the use of physiological measures sensitive to attention and arousal, in conjunction with behavioural and subjective measures, may lead to the design of auditory warnings that produce a sense of urgency in an operator that matches the urgency of the situation.

  13. A psychophysiological evaluation of the perceived urgency of auditory warning signals

    NASA Technical Reports Server (NTRS)

    Burt, J. L.; Bartolome, D. S.; Burdette, D. W.; Comstock, J. R. Jr

    1995-01-01

    One significant concern that pilots have about cockpit auditory warnings is that the signals presently used lack a sense of priority. The relationship between auditory warning sound parameters and perceived urgency is, therefore, an important topic of enquiry in aviation psychology. The present investigation examined the relationship among subjective assessments of urgency, reaction time, and brainwave activity with three auditory warning signals. Subjects performed a tracking task involving automated and manual conditions, and were presented with auditory warnings having various levels of perceived and situational urgency. Subjective assessments revealed that subjects were able to rank warnings on an urgency scale, but rankings were altered after warnings were mapped to a situational urgency scale. Reaction times differed between automated and manual tracking task conditions, and physiological data showed attentional differences in response to perceived and situational warning urgency levels. This study shows that the use of physiological measures sensitive to attention and arousal, in conjunction with behavioural and subjective measures, may lead to the design of auditory warnings that produce a sense of urgency in an operator that matches the urgency of the situation.

  14. Coding of signals in noise by amphibian auditory nerve fibers.

    PubMed

    Narins, P M

    1987-01-01

    Rate-level (R-L) functions derived for pure-tones and pure-tones in broadband noise were obtained for auditory nerve fibers in the treefrog, Eleutherodactylus coqui. Normalized R-L functions for low-frequency, low-threshold fibers exhibit a horizontal rightward shift in the presence of broadband background noise. The magnitude of this shift is directly proportional to the noise spectrum level, and inversely proportional to the fiber's threshold. R-L functions for mid- and high-frequency fibers also show a horizontal shift, but to a lesser degree, consistent with their elevated thresholds relative to the low-frequency fibers. The implications of these findings for the processing of biologically significant sounds in the high levels of background noise in the animal's natural habitat are considered.

  15. Sensitivity of offset and onset cortical auditory evoked potentials to signals in noise.

    PubMed

    Baltzell, Lucas S; Billings, Curtis J

    2014-02-01

    The purpose of this study was to determine the effects of SNR and signal level on the offset response of the cortical auditory evoked potential (CAEP). Successful listening often depends on how well the auditory system can extract target signals from competing background noise. Both signal onsets and offsets are encoded neurally and contribute to successful listening in noise. Neural onset responses to signals in noise demonstrate a strong sensitivity to signal-to-noise ratio (SNR) rather than signal level; however, the sensitivity of neural offset responses to these cues is not known. We analyzed the offset response from two previously published datasets for which only the onset response was reported. For both datasets, CAEPs were recorded from young normal-hearing adults in response to a 1000-Hz tone. For the first dataset, tones were presented at seven different signal levels without background noise, while the second dataset varied both signal level and SNR. Offset responses demonstrated sensitivity to absolute signal level in quiet, SNR, and to absolute signal level in noise. Offset sensitivity to signal level when presented in noise contrasts with previously published onset results. This sensitivity suggests a potential clinical measure of cortical encoding of signal level in noise.

  16. Piglets Learn to Use Combined Human-Given Visual and Auditory Signals to Find a Hidden Reward in an Object Choice Task.

    PubMed

    Bensoussan, Sandy; Cornil, Maude; Meunier-Salaün, Marie-Christine; Tallet, Céline

    2016-01-01

    Although animals rarely use only one sense to communicate, few studies have investigated the use of combinations of different signals between animals and humans. This study assessed for the first time the spontaneous reactions of piglets to human pointing gestures and voice in an object-choice task with a reward. Piglets (Sus scrofa domestica) mainly use auditory signals-individually or in combination with other signals-to communicate with their conspecifics. Their wide hearing range (42 Hz to 40.5 kHz) fits the range of human vocalisations (40 Hz to 1.5 kHz), which may induce sensitivity to the human voice. However, only their ability to use visual signals from humans, especially pointing gestures, has been assessed to date. The current study investigated the effects of signal type (visual, auditory and combined visual and auditory) and piglet experience on the piglets' ability to locate a hidden food reward over successive tests. Piglets did not find the hidden reward at first presentation, regardless of the signal type given. However, they subsequently learned to use a combination of auditory and visual signals (human voice and static or dynamic pointing gestures) to successfully locate the reward in later tests. This learning process may result either from repeated presentations of the combination of static gestures and auditory signals over successive tests, or from transitioning from static to dynamic pointing gestures, again over successive tests. Furthermore, piglets increased their chance of locating the reward either if they did not go straight to a bowl after entering the test area or if they stared at the experimenter before visiting it. Piglets were not able to use the voice direction alone, indicating that a combination of signals (pointing and voice direction) is necessary. Improving our communication with animals requires adapting to their individual sensitivity to human-given signals.

  17. EphB signaling regulates target innervation in the developing and deafferented auditory brainstem

    PubMed Central

    Nakamura, Paul A.; Hsieh, Candace Y.; Cramer, Karina S.

    2012-01-01

    Precision in auditory brainstem connectivity underlies sound localization. Cochlear activity is transmitted to the ventral cochlear nucleus (VCN) in the mammalian brainstem via the auditory nerve. VCN globular bushy cells project to the contralateral medial nucleus of the trapezoid body (MNTB), where specialized axons terminals, the calyces of Held, encapsulate MNTB principal neurons. The VCN-MNTB pathway is an essential component of the circuitry used to compute interaural intensity differences that are used for localizing sounds. When input from one ear is removed during early postnatal development, auditory brainstem circuitry displays robust anatomical plasticity. The molecular mechanisms that control the development of auditory brainstem circuitry and the developmental plasticity of these pathways are poorly understood. In this study we examined the role of EphB signaling in the development of the VCN-MNTB projection and in the reorganization of this pathway after unilateral deafferentation. We found that EphB2 and EphB3 reverse signaling are critical for the normal development of the projection from VCN to MNTB, but that successful circuit assembly most likely relies upon the coordinated function of many EphB proteins. We have also found that ephrin-B reverse signaling repels induced projections to the ipsilateral MNTB after unilateral deafferentation, suggesting that similar mechanisms regulate these two processes. PMID:22021100

  18. Widespread and Opponent fMRI Signals Represent Sound Location in Macaque Auditory Cortex.

    PubMed

    Ortiz-Rios, Michael; Azevedo, Frederico A C; Kuśmierek, Paweł; Balla, Dávid Z; Munk, Matthias H; Keliris, Georgios A; Logothetis, Nikos K; Rauschecker, Josef P

    2017-02-22

    In primates, posterior auditory cortical areas are thought to be part of a dorsal auditory pathway that processes spatial information. But how posterior (and other) auditory areas represent acoustic space remains a matter of debate. Here we provide new evidence based on functional magnetic resonance imaging (fMRI) of the macaque indicating that space is predominantly represented by a distributed hemifield code rather than by a local spatial topography. Hemifield tuning in cortical and subcortical regions emerges from an opponent hemispheric pattern of activation and deactivation that depends on the availability of interaural delay cues. Importantly, these opponent signals allow responses in posterior regions to segregate space similarly to a hemifield code representation. Taken together, our results reconcile seemingly contradictory views by showing that the representation of space follows closely a hemifield code and suggest that enhanced posterior-dorsal spatial specificity in primates might emerge from this form of coding. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Integration of auditory and somatosensory error signals in the neural control of speech movements

    PubMed Central

    Feng, Yongqiang; Gracco, Vincent L.

    2011-01-01

    We investigated auditory and somatosensory feedback contributions to the neural control of speech. In task I, sensorimotor adaptation was studied by perturbing one of these sensory modalities or both modalities simultaneously. The first formant (F1) frequency in the auditory feedback was shifted up by a real-time processor and/or the extent of jaw opening was increased or decreased with a force field applied by a robotic device. All eight subjects lowered F1 to compensate for the up-shifted F1 in the feedback signal regardless of whether or not the jaw was perturbed. Adaptive changes in subjects' acoustic output resulted from adjustments in articulatory movements of the jaw or tongue. Adaptation in jaw opening extent in response to the mechanical perturbation occurred only when no auditory feedback perturbation was applied or when the direction of adaptation to the force was compatible with the direction of adaptation to a simultaneous acoustic perturbation. In tasks II and III, subjects' auditory and somatosensory precision and accuracy were estimated. Correlation analyses showed that the relationships 1) between F1 adaptation extent and auditory acuity for F1 and 2) between jaw position adaptation extent and somatosensory acuity for jaw position were weak and statistically not significant. Taken together, the combined findings from this work suggest that, in speech production, sensorimotor adaptation updates the underlying control mechanisms in such a way that the planning of vowel-related articulatory movements takes into account a complex integration of error signals from previous trials but likely with a dominant role for the auditory modality. PMID:21562187

  20. Integration of auditory and somatosensory error signals in the neural control of speech movements.

    PubMed

    Feng, Yongqiang; Gracco, Vincent L; Max, Ludo

    2011-08-01

    We investigated auditory and somatosensory feedback contributions to the neural control of speech. In task I, sensorimotor adaptation was studied by perturbing one of these sensory modalities or both modalities simultaneously. The first formant (F1) frequency in the auditory feedback was shifted up by a real-time processor and/or the extent of jaw opening was increased or decreased with a force field applied by a robotic device. All eight subjects lowered F1 to compensate for the up-shifted F1 in the feedback signal regardless of whether or not the jaw was perturbed. Adaptive changes in subjects' acoustic output resulted from adjustments in articulatory movements of the jaw or tongue. Adaptation in jaw opening extent in response to the mechanical perturbation occurred only when no auditory feedback perturbation was applied or when the direction of adaptation to the force was compatible with the direction of adaptation to a simultaneous acoustic perturbation. In tasks II and III, subjects' auditory and somatosensory precision and accuracy were estimated. Correlation analyses showed that the relationships 1) between F1 adaptation extent and auditory acuity for F1 and 2) between jaw position adaptation extent and somatosensory acuity for jaw position were weak and statistically not significant. Taken together, the combined findings from this work suggest that, in speech production, sensorimotor adaptation updates the underlying control mechanisms in such a way that the planning of vowel-related articulatory movements takes into account a complex integration of error signals from previous trials but likely with a dominant role for the auditory modality.

  1. Detectability of auditory signals presented without defined observation intervals

    NASA Technical Reports Server (NTRS)

    Watson, C. S.; Nichols, T. L.

    1976-01-01

    Ability to detect tones in noise was measured without defined observation intervals. Latency density functions were estimated for the first response following a signal and, separately, for the first response following randomly distributed instances of background noise. Detection performance was measured by the maximum separation between the cumulative latency density functions for signal-plus-noise and for noise alone. Values of the index of detectability, estimated by this procedure, were approximately those obtained with a 2-dB weaker signal and defined observation intervals. Simulation of defined- and non-defined-interval tasks with an energy detector showed that this device performs very similarly to the human listener in both cases.

  2. Detectability of auditory signals presented without defined observation intervals

    NASA Technical Reports Server (NTRS)

    Watson, C. S.; Nichols, T. L.

    1976-01-01

    Ability to detect tones in noise was measured without defined observation intervals. Latency density functions were estimated for the first response following a signal and, separately, for the first response following randomly distributed instances of background noise. Detection performance was measured by the maximum separation between the cumulative latency density functions for signal-plus-noise and for noise alone. Values of the index of detectability, estimated by this procedure, were approximately those obtained with a 2-dB weaker signal and defined observation intervals. Simulation of defined- and non-defined-interval tasks with an energy detector showed that this device performs very similarly to the human listener in both cases.

  3. Role of the anterior insular cortex in integrative causal signaling during multisensory auditory-visual attention.

    PubMed

    Chen, Tianwen; Michels, Lars; Supekar, Kaustubh; Kochalka, John; Ryali, Srikanth; Menon, Vinod

    2015-01-01

    Coordinated attention to information from multiple senses is fundamental to our ability to respond to salient environmental events, yet little is known about brain network mechanisms that guide integration of information from multiple senses. Here we investigate dynamic causal mechanisms underlying multisensory auditory-visual attention, focusing on a network of right-hemisphere frontal-cingulate-parietal regions implicated in a wide range of tasks involving attention and cognitive control. Participants performed three 'oddball' attention tasks involving auditory, visual and multisensory auditory-visual stimuli during fMRI scanning. We found that the right anterior insula (rAI) demonstrated the most significant causal influences on all other frontal-cingulate-parietal regions, serving as a major causal control hub during multisensory attention. Crucially, we then tested two competing models of the role of the rAI in multisensory attention: an 'integrated' signaling model in which the rAI generates a common multisensory control signal associated with simultaneous attention to auditory and visual oddball stimuli versus a 'segregated' signaling model in which the rAI generates two segregated and independent signals in each sensory modality. We found strong support for the integrated, rather than the segregated, signaling model. Furthermore, the strength of the integrated control signal from the rAI was most pronounced on the dorsal anterior cingulate and posterior parietal cortices, two key nodes of saliency and central executive networks respectively. These results were preserved with the addition of a superior temporal sulcus region involved in multisensory processing. Our study provides new insights into the dynamic causal mechanisms by which the AI facilitates multisensory attention.

  4. Detection of Auditory Signals in Quiet and Noisy Backgrounds while Performing a Visuo-spatial Task

    PubMed Central

    Rawool, Vishakha W.

    2016-01-01

    Context: The ability to detect important auditory signals while performing visual tasks may be further compounded by background chatter. Thus, it is important to know how task performance may interact with background chatter to hinder signal detection. Aim: To examine any interactive effects of speech spectrum noise and task performance on the ability to detect signals. Settings and Design: The setting was a sound-treated booth. A repeated measures design was used. Materials and Methods: Auditory thresholds of 20 normal adults were determined at 0.5, 1, 2 and 4 kHz in the following conditions presented in a random order: (1) quiet with attention; (2) quiet with a visuo-spatial task or puzzle (distraction); (3) noise with attention and (4) noise with task. Statistical Analysis: Multivariate analyses of variance (MANOVA) with three repeated factors (quiet versus noise, visuo-spatial task versus no task, signal frequency). Results: MANOVA revealed significant main effects for noise and signal frequency and significant noise–frequency and task–frequency interactions. Distraction caused by performing the task worsened the thresholds for tones presented at the beginning of the experiment and had no effect on tones presented in the middle. At the end of the experiment, thresholds (4 kHz) were better while performing the task than those obtained without performing the task. These effects were similar across the quiet and noise conditions. Conclusion: Detection of auditory signals is difficult at the beginning of a distracting visuo-spatial task but over time, task learning and auditory training effects can nullify the effect of distraction and may improve detection of high frequency sounds. PMID:27991458

  5. Piglets Learn to Use Combined Human-Given Visual and Auditory Signals to Find a Hidden Reward in an Object Choice Task

    PubMed Central

    Bensoussan, Sandy; Cornil, Maude; Meunier-Salaün, Marie-Christine; Tallet, Céline

    2016-01-01

    Although animals rarely use only one sense to communicate, few studies have investigated the use of combinations of different signals between animals and humans. This study assessed for the first time the spontaneous reactions of piglets to human pointing gestures and voice in an object-choice task with a reward. Piglets (Sus scrofa domestica) mainly use auditory signals–individually or in combination with other signals—to communicate with their conspecifics. Their wide hearing range (42 Hz to 40.5 kHz) fits the range of human vocalisations (40 Hz to 1.5 kHz), which may induce sensitivity to the human voice. However, only their ability to use visual signals from humans, especially pointing gestures, has been assessed to date. The current study investigated the effects of signal type (visual, auditory and combined visual and auditory) and piglet experience on the piglets’ ability to locate a hidden food reward over successive tests. Piglets did not find the hidden reward at first presentation, regardless of the signal type given. However, they subsequently learned to use a combination of auditory and visual signals (human voice and static or dynamic pointing gestures) to successfully locate the reward in later tests. This learning process may result either from repeated presentations of the combination of static gestures and auditory signals over successive tests, or from transitioning from static to dynamic pointing gestures, again over successive tests. Furthermore, piglets increased their chance of locating the reward either if they did not go straight to a bowl after entering the test area or if they stared at the experimenter before visiting it. Piglets were not able to use the voice direction alone, indicating that a combination of signals (pointing and voice direction) is necessary. Improving our communication with animals requires adapting to their individual sensitivity to human-given signals. PMID:27792731

  6. Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an 'interface' nucleus.

    PubMed

    Pawlisch, B A; Remage-Healey, L

    2015-01-22

    Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these

  7. Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an `interface' nucleus

    PubMed Central

    Pawlisch, Benjamin A.; Remage-Healey, Luke

    2014-01-01

    Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher-order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these

  8. Perceptual degradation due to signal alteration: implications for auditory pattern processing.

    PubMed

    Samuel, A G

    1991-05-01

    When a passage is alternately presented to the right and left ears over headphones, perceptual processing is disrupted under certain conditions: When the signal alternation rate is approximately 3-4 cps, intelligibility is greatly reduced. Experiment 1 demonstrated that contrary to previous theorizing, the effect is not mediated by the disruption of syllabic units. Experiment 2 explored the generality of the perceptual degradation by testing perception of simple piano melodies. The basic effect holds for these complex auditory patterns. The final experiment tested a source-effect explanation of the phenomenon by using 3 signal locations (right, middle, and left) rather than 2. The degree of disruption depends on the likelihood that sounds are assigned to different sources. Together, the experiments help to account for the strikingly selective breakdown in perceptual processing and speak to the issues of perceptual units, domain specificity, and auditory source assignment.

  9. Specialized Postsynaptic Morphology Enhances Neurotransmitter Dilution and High-Frequency Signaling at an Auditory Synapse

    PubMed Central

    Graydon, Cole W.; Cho, Soyoun; Diamond, Jeffrey S.; Kachar, Bechara; von Gersdorff, Henrique

    2014-01-01

    Sensory processing in the auditory system requires that synapses, neurons, and circuits encode information with particularly high temporal and spectral precision. In the amphibian papillia, sound frequencies up to 1 kHz are encoded along a tonotopic array of hair cells and transmitted to afferent fibers via fast, repetitive synaptic transmission, thereby promoting phase locking between the presynaptic and postsynaptic cells. Here, we have combined serial section electron microscopy, paired electrophysiological recordings, and Monte Carlo diffusion simulations to examine novel mechanisms that facilitate fast synaptic transmission in the inner ear of frogs (Rana catesbeiana and Rana pipiens). Three-dimensional anatomical reconstructions reveal specialized spine-like contacts between individual afferent fibers and hair cells that are surrounded by large, open regions of extracellular space. Morphologically realistic diffusion simulations suggest that these local enlargements in extracellular space speed transmitter clearance and reduce spillover between neighboring synapses, thereby minimizing postsynaptic receptor desensitization and improving sensitivity during prolonged signal transmission. Additionally, evoked EPSCs in afferent fibers are unaffected by glutamate transporter blockade, suggesting that transmitter diffusion and dilution, and not uptake, play a primary role in speeding neurotransmission and ensuring fidelity at these synapses. PMID:24920639

  10. Perception-based multi-resolution auditory processing of acoustic signals

    NASA Astrophysics Data System (ADS)

    Ru, Po-Wen

    2000-10-01

    A multi-resolution auditory model is proposed to simulate the spectrotemporal processing of the primary auditory cortex. Inspired by recent physiological findings, the model produces a multi-dimensional representation of cortical activity. Though several nonlinear operations are involved, the inversion of the representation is obtained by applying convex projection technique. A series of psychoacoustical experiments were conducted to estimate the appropriate units for the axes of this auditory model. The ``perceptual distance'' measure, which was derived from the subjective results, outperforms the independent channel model in threshold prediction tasks. Additionally, a simplified vocal tract model was employed to explore the articulatory equivalence to the cortical axes. This study suggests that both local and global changes in the geometry of the vocal tract result in meaningful changes in the cortical response. The perceptual distance measure, when applied to vowel recognition and timbre quantification, yields better performance than conventional signal processing techniques. Given enough computing power, this perception-based auditory model can be used in many applications like speech recognition, audio coding, and sound identification.

  11. Vocalization-whisking coordination and multisensory integration of social signals in rat auditory cortex.

    PubMed

    Rao, Rajnish P; Mielke, Falk; Bobrov, Evgeny; Brecht, Michael

    2014-12-08

    Social interactions involve multi-modal signaling. Here, we study interacting rats to investigate audio-haptic coordination and multisensory integration in the auditory cortex. We find that facial touch is associated with an increased rate of ultrasonic vocalizations, which are emitted at the whisking rate (∼8 Hz) and preferentially initiated in the retraction phase of whisking. In a small subset of auditory cortex regular-spiking neurons, we observed excitatory and heterogeneous responses to ultrasonic vocalizations. Most fast-spiking neurons showed a stronger response to calls. Interestingly, facial touch-induced inhibition in the primary auditory cortex and off-responses after termination of touch were twofold stronger than responses to vocalizations. Further, touch modulated the responsiveness of auditory cortex neurons to ultrasonic vocalizations. In summary, facial touch during social interactions involves precisely orchestrated calling-whisking patterns. While ultrasonic vocalizations elicited a rather weak population response from the regular spikers, the modulation of neuronal responses by facial touch was remarkably strong.

  12. Vocalization–whisking coordination and multisensory integration of social signals in rat auditory cortex

    PubMed Central

    Rao, Rajnish P; Mielke, Falk; Bobrov, Evgeny; Brecht, Michael

    2014-01-01

    Social interactions involve multi-modal signaling. Here, we study interacting rats to investigate audio-haptic coordination and multisensory integration in the auditory cortex. We find that facial touch is associated with an increased rate of ultrasonic vocalizations, which are emitted at the whisking rate (∼8 Hz) and preferentially initiated in the retraction phase of whisking. In a small subset of auditory cortex regular-spiking neurons, we observed excitatory and heterogeneous responses to ultrasonic vocalizations. Most fast-spiking neurons showed a stronger response to calls. Interestingly, facial touch-induced inhibition in the primary auditory cortex and off-responses after termination of touch were twofold stronger than responses to vocalizations. Further, touch modulated the responsiveness of auditory cortex neurons to ultrasonic vocalizations. In summary, facial touch during social interactions involves precisely orchestrated calling-whisking patterns. While ultrasonic vocalizations elicited a rather weak population response from the regular spikers, the modulation of neuronal responses by facial touch was remarkably strong. DOI: http://dx.doi.org/10.7554/eLife.03185.001 PMID:25485525

  13. The superior temporal sulcus differentiates communicative and noncommunicative auditory signals.

    PubMed

    Shultz, Sarah; Vouloumanos, Athena; Pelphrey, Kevin

    2012-05-01

    Processing the vocalizations of conspecifics is critical for adaptive social interaction. A species-specific voice-selective region has been identified in the right STS that responds more strongly to human vocal sounds compared with a variety of nonvocal sounds. However, the STS also activates in response to a wide range of signals used in communication, such as eye gaze, biological motion, and speech. These findings raise the possibility that the voice-selective region of the STS may be especially sensitive to vocal sounds that are communicative, rather than to all human vocal sounds. Using fMRI, we demonstrate that the voice-selective region of the STS responds more strongly to communicative vocal sounds (such as speech and laughter) compared with noncommunicative vocal sounds (such as coughing and sneezing). The implications of these results for understanding the role of the STS in voice processing and in disorders of social communication, such as autism spectrum disorder, are discussed.

  14. EphA Signaling Impacts Development of Topographic Connectivity in Auditory Corticofugal Systems

    PubMed Central

    Hackett, Troy A.; Rakic, Pasko; Levitt, Pat; Polley, Daniel B.

    2013-01-01

    Auditory stimulus representations are dynamically maintained by ascending and descending projections linking the auditory cortex (Actx), medial geniculate body (MGB), and inferior colliculus. Although the extent and topographic specificity of descending auditory corticofugal projections can equal or surpass that of ascending corticopetal projections, little is known about the molecular mechanisms that guide their development. Here, we used in utero gene electroporation to examine the role of EphA receptor signaling in the development of corticothalamic (CT) and corticocollicular connections. Early in postnatal development, CT axons were restricted to a deep dorsal zone (DDZ) within the MGB that expressed low levels of the ephrin-A ligand. By hearing onset, CT axons had innervated surrounding regions of MGB in control-electroporated mice but remained fixed within the DDZ in mice overexpressing EphA7. In vivo neurophysiological recordings demonstrated a corresponding reduction in spontaneous firing rate, but no changes in sound-evoked responsiveness within MGB regions deprived of CT innervation. Structural and functional CT disruption occurred without gross alterations in thalamocortical connectivity. These data demonstrate a potential role for EphA/ephrin-A signaling in the initial guidance of corticofugal axons and suggest that “genetic rewiring” may represent a useful functional tool to alter cortical feedback without silencing Actx. PMID:22490549

  15. AUX: a scripting language for auditory signal processing and software packages for psychoacoustic experiments and education.

    PubMed

    Kwon, Bomjun J

    2012-06-01

    This article introduces AUX (AUditory syntaX), a scripting syntax specifically designed to describe auditory signals and processing, to the members of the behavioral research community. The syntax is based on descriptive function names and intuitive operators suitable for researchers and students without substantial training in programming, who wish to generate and examine sound signals using a written script. In this article, the essence of AUX is discussed and practical examples of AUX scripts specifying various signals are illustrated. Additionally, two accompanying Windows-based programs and development libraries are described. AUX Viewer is a program that generates, visualizes, and plays sounds specified in AUX. AUX Viewer can also be used for class demonstrations or presentations. Another program, Psycon, allows a wide range of sound signals to be used as stimuli in common psychophysical testing paradigms, such as the adaptive procedure, the method of constant stimuli, and the method of adjustment. AUX Library is also provided, so that researchers can develop their own programs utilizing AUX. The philosophical basis of AUX is to separate signal generation from the user interface needed for experiments. AUX scripts are portable and reusable; they can be shared by other researchers, regardless of differences in actual AUX-based programs, and reused for future experiments. In short, the use of AUX can be potentially beneficial to all members of the research community-both those with programming backgrounds and those without.

  16. Human Engineer’s Guide to Auditory Displays. Volume 2. Elements of Signal Reception and Resolution Affecting Auditory Displays.

    DTIC Science & Technology

    1984-08-01

    0011/0037-2 signal’s energy about its central frequency, an effect which may be demonstrated either physically or mathematically. As pointed out by...fatigue occurs as a linear function of log-time (Plomp, 1964a). Decay functions that are linear over time also have been reported (e.g., Luscher and...required to achieve threshold. 10 .-,- - NAVTRAEQUIPCEN 80-D-0011/0037-2 Under conditions of simultaneous masking the signal and masker are physically

  17. Effects of Signal-to-Noise Ratio on Auditory Cortical Frequency Processing

    PubMed Central

    Teschner, Magnus J.; Seybold, Bryan A.; Malone, Brian J.; Hüning, Jana

    2016-01-01

    The neural mechanisms that support the robust processing of acoustic signals in the presence of background noise in the auditory system remain largely unresolved. Psychophysical experiments have shown that signal detection is influenced by the signal-to-noise ratio (SNR) and the overall stimulus level, but this relationship has not been fully characterized. We evaluated the neural representation of frequency in rat primary auditory cortex by constructing tonal frequency response areas (FRAs) in primary auditory cortex for different SNRs, tone levels, and noise levels. We show that response strength and selectivity for frequency and sound level depend on interactions between SNRs and tone levels. At low SNRs, jointly increasing the tone and noise levels reduced firing rates and narrowed FRA bandwidths; at higher SNRs, however, increasing the tone and noise levels increased firing rates and expanded bandwidths, as is usually seen for FRAs obtained without background noise. These changes in frequency and intensity tuning decreased tone level and tone frequency discriminability at low SNRs. By contrast, neither response onset latencies nor noise-driven steady-state firing rates meaningfully interacted with SNRs or overall sound levels. Speech detection performance in humans was also shown to depend on the interaction between overall sound level and SNR. Together, these results indicate that signal processing difficulties imposed by high noise levels are quite general and suggest that the neurophysiological changes we see for simple sounds generalize to more complex stimuli. SIGNIFICANCE STATEMENT Effective processing of sounds in background noise is an important feature of the mammalian auditory system and a necessary feature for successful hearing in many listening conditions. Even mild hearing loss strongly affects this ability in humans, seriously degrading the ability to communicate. The mechanisms involved in achieving high performance in background noise are not

  18. Suppressed visual looming stimuli are not integrated with auditory looming signals: Evidence from continuous flash suppression.

    PubMed

    Moors, Pieter; Huygelier, Hanne; Wagemans, Johan; de-Wit, Lee; van Ee, Raymond

    2015-01-01

    Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS) have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.

  19. What you see isn't always what you get: Auditory word signals trump consciously perceived words in lexical access.

    PubMed

    Ostrand, Rachel; Blumstein, Sheila E; Ferreira, Victor S; Morgan, James L

    2016-06-01

    Human speech perception often includes both an auditory and visual component. A conflict in these signals can result in the McGurk illusion, in which the listener perceives a fusion of the two streams, implying that information from both has been integrated. We report two experiments investigating whether auditory-visual integration of speech occurs before or after lexical access, and whether the visual signal influences lexical access at all. Subjects were presented with McGurk or Congruent primes and performed a lexical decision task on related or unrelated targets. Although subjects perceived the McGurk illusion, McGurk and Congruent primes with matching real-word auditory signals equivalently primed targets that were semantically related to the auditory signal, but not targets related to the McGurk percept. We conclude that the time course of auditory-visual integration is dependent on the lexicality of the auditory and visual input signals, and that listeners can lexically access one word and yet consciously perceive another.

  20. Calcium Signaling Is Required for Erythroid Enucleation.

    PubMed

    Wölwer, Christina B; Pase, Luke B; Russell, Sarah M; Humbert, Patrick O

    2016-01-01

    Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM) pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation.

  1. Calcium Signaling Is Required for Erythroid Enucleation

    PubMed Central

    Russell, Sarah M.; Humbert, Patrick O.

    2016-01-01

    Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM) pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation. PMID:26731108

  2. Searching for a talking face: the effect of degrading the auditory signal.

    PubMed

    Stacey, Paula C; Murphy, Thomas; Sumner, Christian J; Kitterick, Pádraig T; Roberts, Katherine L

    2014-12-01

    Previous research (e.g., McGurk & MacDonald, 1976) suggests that faces and voices are bound automatically, but recent evidence suggests that attention is involved in a task of searching for a talking face (Alsius & Soto-Faraco, 2011). We hypothesized that the processing demands of the stimuli may affect the amount of attentional resources required, and investigated what effect degrading the auditory stimulus had on the time taken to locate a talking face. Twenty participants were presented with between 2 and 4 faces articulating different sentences, and had to decide which of these faces matched the sentence that they heard. The results showed that in the least demanding auditory condition (clear speech in quiet), search times did not significantly increase when the number of faces increased. However, when speech was presented in background noise or was processed to simulate the information provided by a cochlear implant, search times increased as the number of faces increased. Thus, it seems that the amount of attentional resources required vary according to the processing demands of the auditory stimuli, and when processing load is increased then faces need to be individually attended to in order to complete the task. Based on these results we would expect cochlear-implant users to find the task of locating a talking face more attentionally demanding than normal hearing listeners.

  3. Frontal top-down signals increase coupling of auditory low-frequency oscillations to continuous speech in human listeners.

    PubMed

    Park, Hyojin; Ince, Robin A A; Schyns, Philippe G; Thut, Gregor; Gross, Joachim

    2015-06-15

    Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception.

  4. The perceived quality of in-vehicle auditory signals: a structural equation modelling approach.

    PubMed

    Chi, Chia-Fen; Dewi, Ratna Sari; Surbakti, Yopie Yutama; Hsieh, Dong-Yu

    2017-11-01

    The current study applied Structural Equation Modelling to analyse the relationship among pitch, loudness, tempo and timbre and their relationship with perceived sound quality. Twenty-eight auditory signals of horn, indicator, door open warning and parking sensor were collected from 11 car brands. Twenty-one experienced drivers were recruited to evaluate all sound signals with 11 semantic differential scales. The results indicate that for the continuous sounds, pitch, loudness and timbre each had a direct impact on the perceived quality. Besides the direct impacts, pitch also had an impact on loudness perception. For the intermittent sounds, tempo and timbre each had a direct impact on the perceived quality. These results can help to identify the psychoacoustic attributes affecting the consumers' quality perception and help to design preferable sounds for vehicles. In the end, a design guideline is proposed for the development of auditory signals that adopts the current study's research findings as well as those of other relevant research. Practitioner Summary: This study applied Structural Equation Modelling to analyse the relationship among pitch, loudness, tempo and timbre and their relationship with perceived sound quality. The result can help to identify psychoacoustic attributes affecting the consumers' quality perception and help to design preferable sounds for vehicles.

  5. A mechanism for detecting coincidence of auditory and visual spatial signals.

    PubMed

    Orchard-Mills, Emily; Leung, Johahn; Burr, David; Morrone, Maria Concetta; Wufong, Ella; Carlile, Simon; Alais, David

    2013-01-01

    Information about the world is captured by our separate senses, and must be integrated to yield a unified representation. This raises the issue of which signals should be integrated and which should remain separate, as inappropriate integration will lead to misrepresentation and distortions. One strong cue suggesting that separate signals arise from a single source is coincidence, in space and in time. We measured increment thresholds for discriminating spatial intervals defined by pairs of simultaneously presented targets, one flash and one auditory sound, for various separations. We report a 'dipper function', in which thresholds follow a 'U-shaped' curve, with thresholds initially decreasing with spatial interval, and then increasing for larger separations. The presence of a dip in the audiovisual increment-discrimination function is evidence that the auditory and visual signals both input to a common mechanism encoding spatial separation, and a simple filter model with a sigmoidal transduction function simulated the results well. The function of an audiovisual spatial filter may be to detect coincidence, a fundamental cue guiding whether to integrate or segregate.

  6. atonal is required for exoskeletal joint formation in the Drosophila auditory system.

    PubMed

    Göpfert, M C; Stocker, H; Robert, D

    2002-09-01

    Hearing relies on the delicate arrangement of mechanoreceptor neurones and an acoustomechanical interface. The concerted action of these neural and non-neural components is essential to audition, raising the question of whether they also develop in a concerted way. Drosophila hears with its antennae. A specialized antennal joint allows the distal part of the antenna to vibrate in response to sound and, thus, to serve as the sound receiver. This receiver's vibration is transduced by a chordotonal sense organ (CHO) that is closely associated with the joint. Here, we report that atonal (ato), the proneural gene for CHOs, is required for the formation of this antennal joint. Biophysical measurements in hemi- and homozygous ato(1) mutant flies show that, in addition to eliminating the auditory CHO, loss of ato function makes the antennal receiver insensitive to sound, impairing its auditory function. Anatomically, the cause for this mechanical effect resides in the deprivation of mobile exoskeletal joint structures. Hence, ato, the homologue of mouse Math1, is required for the formation of both the auditory CHO and joint, providing a genetic link between the very neural and exoskeletal components that together transform fly antennae into ears. Copyright 2002 Wiley-Liss, Inc.

  7. The Role of Amygdala Nuclei in the Expression of Auditory Signaled Two-Way Active Avoidance in Rats

    ERIC Educational Resources Information Center

    Choi, June-Seek; Cain, Christopher K.; LeDoux, Joseph E.

    2010-01-01

    Using a two-way signaled active avoidance (2-AA) learning procedure, where rats were trained in a shuttle box to avoid a footshock signaled by an auditory stimulus, we tested the contributions of the lateral (LA), basal (B), and central (CE) nuclei of the amygdala to the expression of instrumental active avoidance conditioned responses (CRs).…

  8. The Role of Amygdala Nuclei in the Expression of Auditory Signaled Two-Way Active Avoidance in Rats

    ERIC Educational Resources Information Center

    Choi, June-Seek; Cain, Christopher K.; LeDoux, Joseph E.

    2010-01-01

    Using a two-way signaled active avoidance (2-AA) learning procedure, where rats were trained in a shuttle box to avoid a footshock signaled by an auditory stimulus, we tested the contributions of the lateral (LA), basal (B), and central (CE) nuclei of the amygdala to the expression of instrumental active avoidance conditioned responses (CRs).…

  9. Decision-related cortical potentials during an auditory signal detection task with cued observation intervals

    NASA Technical Reports Server (NTRS)

    Squires, K. C.; Squires, N. K.; Hillyard, S. A.

    1975-01-01

    Cortical-evoked potentials were recorded from human subjects performing an auditory detection task with confidence rating responses. Unlike earlier studies that used similar procedures, the observation interval during which the auditory signal could occur was clearly marked by a visual cue light. By precisely defining the observation interval and, hence, synchronizing all perceptual decisions to the evoked potential averaging epoch, it was possible to demonstrate that high-confidence false alarms are accompanied by late-positive P3 components equivalent to those for equally confident hits. Moreover the hit and false alarm evoked potentials were found to covary similarly with variations in confidence rating and to have similar amplitude distributions over the scalp. In a second experiment, it was demonstrated that correct rejections can be associated with a P3 component larger than that for hits. Thus it was possible to show, within the signal detection paradigm, how the two major factors of decision confidence and expectancy are reflected in the P3 component of the cortical-evoked potential.

  10. Bi-hemispheric study of single trial MEG signals of the human auditory cortex.

    PubMed

    Liu, L C; Ioannides, A A; Müller-Gärtner, H W

    1998-01-01

    Auditory evoked magnetic fields were recorded from 5 human subjects, simultaneously over each hemisphere, using the BTi twin MAGNES system (2 x 37 channel). Accurate placing of each probe and the use of optimally designed linear sums of signals allow the estimation of the millisecond by millisecond history of activation of the complex of generators responsible for the M100 response in each single trial. Thus it can be shown in much greater detail than any study so far, how the average signal around the M100 period is built up by events in single trials. We found consistent features across subjects, defining a dynamic baseline from which the stimulus related activity can be differentiated. Our analysis indicates that prior to the stimulus onset the activity in each auditory cortex proceeds more or less independently. The onset of the stimulus establishes a binding of activity in the two hemispheres, probably through a common input. The coordinated activity is well described by an exponentially saturating function with a characteristic time constant in the 'magic' 15-30 ms range.

  11. Auditory detection and discrimination in deaf cats: psychophysical and neural thresholds for intracochlear electrical signals.

    PubMed

    Vollmer, M; Beitel, R E; Snyder, R L

    2001-11-01

    More than 30,000 hearing-impaired human subjects have learned to use cochlear implants for speech perception and speech discrimination. To understand the basic mechanisms underlying the successful application of contemporary speech processing strategies, it is important to investigate how complex electrical stimuli delivered to the cochlea are processed and represented in the central auditory system. A deaf animal model has been developed that allows direct comparison of psychophysical thresholds with central auditory neuronal thresholds to temporally modulated intracochlear electrical signals in the same animals. Behavioral detection thresholds were estimated in neonatally deafened cats for unmodulated pulse trains (e.g., 30 pulses/s or pps) and sinusoidal amplitude-modulated (SAM) pulse trains (e.g., 300 pps, SAM at 30 Hz; 300/30 AM). Animals were trained subsequently in a discrimination task to respond to changes in the modulation frequency of successive SAM signals (e.g., 300/8 AM vs. 300/30 AM). During acute physiological experiments, neural thresholds to pulse trains were estimated in the inferior colliculus (IC) and the primary auditory cortex (A1) of the anesthetized animals. Psychophysical detection thresholds for unmodulated and SAM pulse trains were virtually identical. Single IC neuron thresholds for SAM pulse trains showed a small but significant increase in threshold (0.4 dB or 15.5 microA) when compared with thresholds for unmodulated pulse trains. The mean difference between psychophysical and minimum neural thresholds within animals was not significant (mean = 0.3 dB). Importantly, cats also successfully discriminated changes in the modulation frequencies of the SAM signals. Performance on the discrimination task was not affected by carrier rate (100, 300, 500, 1,000, or 1,500 pps). These findings indicate that 1) behavioral and neural response thresholds are based on detection of the peak pulse amplitudes of the modulated and unmodulated signals

  12. Analysis of the influence of memory content of auditory stimuli on the memory content of EEG signal

    PubMed Central

    Namazi, Hamidreza; Kulish, Vladimir V.

    2016-01-01

    One of the major challenges in brain research is to relate the structural features of the auditory stimulus to structural features of Electroencephalogram (EEG) signal. Memory content is an important feature of EEG signal and accordingly the brain. On the other hand, the memory content can also be considered in case of stimulus. Beside all works done on analysis of the effect of stimuli on human EEG and brain memory, no work discussed about the stimulus memory and also the relationship that may exist between the memory content of stimulus and the memory content of EEG signal. For this purpose we consider the Hurst exponent as the measure of memory. This study reveals the plasticity of human EEG signals in relation to the auditory stimuli. For the first time we demonstrated that the memory content of an EEG signal shifts towards the memory content of the auditory stimulus used. The results of this analysis showed that an auditory stimulus with higher memory content causes a larger increment in the memory content of an EEG signal. For the verification of this result, we benefit from approximate entropy as indicator of time series randomness. The capability, observed in this research, can be further investigated in relation to human memory. PMID:27528219

  13. Analysis of the influence of memory content of auditory stimuli on the memory content of EEG signal.

    PubMed

    Namazi, Hamidreza; Khosrowabadi, Reza; Hussaini, Jamal; Habibi, Shaghayegh; Farid, Ali Akhavan; Kulish, Vladimir V

    2016-08-30

    One of the major challenges in brain research is to relate the structural features of the auditory stimulus to structural features of Electroencephalogram (EEG) signal. Memory content is an important feature of EEG signal and accordingly the brain. On the other hand, the memory content can also be considered in case of stimulus. Beside all works done on analysis of the effect of stimuli on human EEG and brain memory, no work discussed about the stimulus memory and also the relationship that may exist between the memory content of stimulus and the memory content of EEG signal. For this purpose we consider the Hurst exponent as the measure of memory. This study reveals the plasticity of human EEG signals in relation to the auditory stimuli. For the first time we demonstrated that the memory content of an EEG signal shifts towards the memory content of the auditory stimulus used. The results of this analysis showed that an auditory stimulus with higher memory content causes a larger increment in the memory content of an EEG signal. For the verification of this result, we benefit from approximate entropy as indicator of time series randomness. The capability, observed in this research, can be further investigated in relation to human memory.

  14. 78 FR 36738 - Signal System Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ...., Monday through Friday, except Federal holidays. FOR FURTHER INFORMATION CONTACT: Sean Crain, Electronic Engineer, Signal and Train Control Division, Office of Railroad Safety, FRA, 1200 New Jersey Avenue SE... Report form into an electronic format. The electronic form required all of the same information as...

  15. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance

    PubMed Central

    Buran, Bradley N.; Sen, Kamal; Semple, Malcolm N.; Sanes, Dan H.

    2016-01-01

    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. SIGNIFICANCE STATEMENT The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we

  16. Recurrence of task set-related MEG signal patterns during auditory working memory.

    PubMed

    Peters, Benjamin; Bledowski, Christoph; Rieder, Maria; Kaiser, Jochen

    2016-06-01

    Processing of auditory spatial and non-spatial information in working memory has been shown to rely on separate cortical systems. While previous studies have demonstrated differences in spatial versus non-spatial processing from the encoding of to-be-remembered stimuli onwards, here we investigated whether such differences would be detectable already prior to presentation of the sample stimulus. We analyzed broad-band magnetoencephalography data from 15 healthy adults during an auditory working memory paradigm starting with a visual cue indicating the task-relevant stimulus feature for a given trial (lateralization or pitch) and a subsequent 1.5-s pre-encoding phase. This was followed by a sample sound (0.2s), the delay phase (0.8s) and a test stimulus (0.2s) after which participants made a match/non-match decision. Linear discriminant functions were trained to decode task-specific signal patterns throughout the task, and temporal generalization was used to assess whether the neural codes discriminating between the tasks during the pre-encoding phase would recur during later task periods. The spatial versus non-spatial tasks could indeed be discriminated after the onset of the cue onwards, and decoders trained during the pre-encoding phase successfully discriminated the tasks during both sample stimulus encoding and during the delay phase. This demonstrates that task-specific neural codes are established already before the memorandum is presented and that the same patterns are reestablished during stimulus encoding and maintenance. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance.

    PubMed

    von Trapp, Gardiner; Buran, Bradley N; Sen, Kamal; Semple, Malcolm N; Sanes, Dan H

    2016-10-26

    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity.

  18. Inhibition in the auditory brainstem enhances signal representation and regulates gain in complex acoustic environments

    PubMed Central

    Keine, Christian; Rübsamen, Rudolf; Englitz, Bernhard

    2016-01-01

    Inhibition plays a crucial role in neural signal processing, shaping and limiting responses. In the auditory system, inhibition already modulates second order neurons in the cochlear nucleus, e.g. spherical bushy cells (SBCs). While the physiological basis of inhibition and excitation is well described, their functional interaction in signal processing remains elusive. Using a combination of in vivo loose-patch recordings, iontophoretic drug application, and detailed signal analysis in the Mongolian Gerbil, we demonstrate that inhibition is widely co-tuned with excitation, and leads only to minor sharpening of the spectral response properties. Combinations of complex stimuli and neuronal input-output analysis based on spectrotemporal receptive fields revealed inhibition to render the neuronal output temporally sparser and more reproducible than the input. Overall, inhibition plays a central role in improving the temporal response fidelity of SBCs across a wide range of input intensities and thereby provides the basis for high-fidelity signal processing. DOI: http://dx.doi.org/10.7554/eLife.19295.001 PMID:27855778

  19. Increased Signal Complexity Improves the Breadth of Generalization in Auditory Perceptual Learning

    PubMed Central

    Brown, David J.; Proulx, Michael J.

    2013-01-01

    Perceptual learning can be specific to a trained stimulus or optimally generalized to novel stimuli with the breadth of generalization being imperative for how we structure perceptual training programs. Adapting an established auditory interval discrimination paradigm to utilise complex signals, we trained human adults on a standard interval for either 2, 4, or 10 days. We then tested the standard, alternate frequency, interval, and stereo input conditions to evaluate the rapidity of specific learning and breadth of generalization over the time course. In comparison with previous research using simple stimuli, the speed of perceptual learning and breadth of generalization were more rapid and greater in magnitude, including novel generalization to an alternate temporal interval within stimulus type. We also investigated the long term maintenance of learning and found that specific and generalized learning was maintained over 3 and 6 months. We discuss these findings regarding stimulus complexity in perceptual learning and how they can inform the development of effective training protocols. PMID:24349800

  20. The tradeoff between signal detection and recognition rules auditory sensitivity under variable background noise conditions.

    PubMed

    Lugli, Marco

    2015-12-07

    Animal acoustic communication commonly takes place under masked conditions. For instance, sound signals relevant for mating and survival are very often masked by background noise, which makes their detection and recognition by organisms difficult. Ambient noise (AN) varies in level and shape among different habitats, but also remarkable variations in time and space occurs within the same habitat. Variable AN conditions mask hearing thresholds of the receiver in complex and unpredictable ways, thereby causing distortions in sound perception. When communication takes place in a noisy environment, a highly sensitive system might confer no advantage to the receiver compared to a less sensitive one. The effects of noise masking on auditory thresholds and hearing-related functions are well known, and the potential role of AN in the evolution of the species' auditory sensitivity has been recognized by few authors. The mechanism of the underlying selection process has never been explored, however. Here I present a simple fitness model that seeks for the best sensitivity of a hearing system performing the detection and recognition of the sound under variable AN conditions. The model predicts higher sensitivity (i.e. lower hearing thresholds) as best strategy for species living in quiet habitats and lower sensitivity (i.e. higher hearing thresholds) as best strategy for those living in noisy habitats provided the cost of incorrect recognition is not low. The tradeoff between detection and recognition of acoustic signals appears to be a key factor determining the best level of hearing sensitivity of a species when acoustic communication is corrupted by noise. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Subthreshold membrane responses underlying sparse spiking to natural vocal signals in auditory cortex

    PubMed Central

    Perks, Krista Eva; Gentner, Timothy Q.

    2015-01-01

    Natural acoustic communication signals, such as speech, are typically high-dimensional with a wide range of co-varying spectro-temporal features at multiple timescales. The synaptic and network mechanisms for encoding these complex signals are largely unknown. We are investigating these mechanisms in high-level sensory regions of the songbird auditory forebrain, where single neurons show sparse, object-selective spiking responses to conspecific songs. Using whole-cell in-vivo patch clamp techniques in the caudal mesopallium and the caudal nidopallium of starlings, we examine song-driven subthreshold and spiking activity. We find that both the subthreshold and the spiking activity are reliable (i.e., the same song drives a similar response each time it is presented) and specific (i.e. responses to different songs are distinct). Surprisingly, however, the reliability and specificity of the sub-threshold response was uniformly high regardless of when the cell spiked, even for song stimuli that drove no spikes. We conclude that despite a selective and sparse spiking response, high-level auditory cortical neurons are under continuous, non-selective, stimulus-specific synaptic control. To investigate the role of local network inhibition in this synaptic control, we then recorded extracellularly while pharmacologically blocking local GABA-ergic transmission. This manipulation modulated the strength and the reliability of stimulus-driven spiking, consistent with a role for local inhibition in regulating the reliability of network activity and the stimulus specificity of the subthreshold response in single cells. We discuss these results in the context of underlying computations that could generate sparse, stimulus-selective spiking responses, and models for hierarchical pooling. PMID:25728189

  2. Intensity invariance properties of auditory neurons compared to the statistics of relevant natural signals in grasshoppers.

    PubMed

    Clemens, Jan; Weschke, Gerroth; Vogel, Astrid; Ronacher, Bernhard

    2010-04-01

    The temporal pattern of amplitude modulations (AM) is often used to recognize acoustic objects. To identify objects reliably, intensity invariant representations have to be formed. We approached this problem within the auditory pathway of grasshoppers. We presented AM patterns modulated at different time scales and intensities. Metric space analysis of neuronal responses allowed us to determine how well, how invariantly, and at which time scales AM frequency is encoded. We find that in some neurons spike-count cues contribute substantially (20-60%) to the decoding of AM frequency at a single intensity. However, such cues are not robust when intensity varies. The general intensity invariance of the system is poor. However, there exists a range of AM frequencies around 83 Hz where intensity invariance of local interneurons is relatively high. In this range, natural communication signals exhibit much variation between species, suggesting an important behavioral role for this frequency band. We hypothesize, just as has been proposed for human speech, that the communication signals might have evolved to match the processing properties of the receivers. This contrasts with optimal coding theory, which postulates that neuronal systems are adapted to the statistics of the relevant signals.

  3. Transmembrane channel-like (TMC) genes are required for auditory and vestibular mechanosensation.

    PubMed

    Kawashima, Yoshiyuki; Kurima, Kiyoto; Pan, Bifeng; Griffith, Andrew J; Holt, Jeffrey R

    2015-01-01

    Mutations of the transmembrane channel-like 1 (TMC1) gene can cause dominant and recessive forms of deafness in humans and mice. TMC1 is one of eight mammalian TMC genes of unknown function. The multi-pass transmembrane topologic structure of the proteins they encode suggests roles as a receptor, transporter, channel, or pump. Tmc1 and the closely related Tmc2 gene are expressed in neurosensory hair cells of the auditory and vestibular end organs of the mouse inner ear. Recent studies have demonstrated that Tmc1 and Tmc2 are specifically required for mechanoelectrical transduction in hair cells. The exact role of these proteins in mechanoelectrical transduction is unknown. TMC1 and TMC2 are viable candidates for the mechanoelectrical transduction channel of hair cells, whose component molecules have eluded identification for over 30 years. We expect that studies of TMC proteins will yield insights into molecular components and mechanisms of mechanosensation in auditory and vestibular hair cells, as well as in other tissues and organs.

  4. Effects of sensorineural hearing loss on temporal coding of narrowband and broadband signals in the auditory periphery

    PubMed Central

    Henry, Kenneth S.; Heinz, Michael G.

    2013-01-01

    People with sensorineural hearing loss have substantial difficulty understanding speech under degraded listening conditions. Behavioral studies suggest that this difficulty may be caused by changes in auditory processing of the rapidly-varying temporal fine structure (TFS) of acoustic signals. In this paper, we review the presently known effects of sensorineural hearing loss on processing of TFS and slower envelope modulations in the peripheral auditory system of mammals. Cochlear damage has relatively subtle effects on phase locking by auditory-nerve fibers to the temporal structure of narrowband signals under quiet conditions. In background noise, however, sensorineural loss does substantially reduce phase locking to the TFS of pure-tone stimuli. For auditory processing of broadband stimuli, sensorineural hearing loss has been shown to severely alter the neural representation of temporal information along the tonotopic axis of the cochlea. Notably, auditory-nerve fibers innervating the high-frequency part of the cochlea grow increasingly responsive to low-frequency TFS information and less responsive to temporal information near their characteristic frequency (CF). Cochlear damage also increases the correlation of the response to TFS across fibers of varying CF, decreases the traveling-wave delay between TFS responses of fibers with different CFs, and can increase the range of temporal modulation frequencies encoded in the periphery for broadband sounds. Weaker neural coding of temporal structure in background noise and degraded coding of broadband signals along the tonotopic axis of the cochlea are expected to contribute considerably to speech perception problems in people with sensorineural hearing loss. PMID:23376018

  5. 33 CFR 175.110 - Visual distress signals required.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Visual distress signals required... (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.110 Visual distress signals... signals selected from the list in § 175.130 or the alternatives in § 175.135, in the number required, are...

  6. 33 CFR 175.110 - Visual distress signals required.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Visual distress signals required... (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.110 Visual distress signals... signals selected from the list in § 175.130 or the alternatives in § 175.135, in the number required, are...

  7. 33 CFR 175.110 - Visual distress signals required.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Visual distress signals required... (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.110 Visual distress signals... signals selected from the list in § 175.130 or the alternatives in § 175.135, in the number required, are...

  8. 33 CFR 175.110 - Visual distress signals required.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Visual distress signals required... (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.110 Visual distress signals... signals selected from the list in § 175.130 or the alternatives in § 175.135, in the number required, are...

  9. 33 CFR 175.110 - Visual distress signals required.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Visual distress signals required... (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.110 Visual distress signals... signals selected from the list in § 175.130 or the alternatives in § 175.135, in the number required, are...

  10. Habitat-related differences in auditory processing of complex tones and vocal signal properties in four songbirds.

    PubMed

    Lucas, Jeffrey R; Vélez, Alejandro; Henry, Kenneth S

    2015-04-01

    We examined temporal processing of harmonic tone complexes in two woodland species (tufted titmice and white-breasted nuthatches) and two open-habitat species (house sparrows and white-crowned sparrows). Envelope and fine-structure processing were quantified using the envelope following response (EFR) and frequency following response (FFR). We predicted stronger EFRs in the open-habitat species based on broader auditory filters and greater amplitude modulation of vocal signals in this group. We predicted stronger FFRs in woodland species based on narrower auditory filters. As predicted, EFR amplitude was generally greatest in the open habitat species. FFR amplitude, in contrast, was greatest in white-crowned sparrows with no clear difference between habitats. This result cannot be fully explained by species differences in audiogram shape and might instead reflect greater acoustic complexity of songs in the white-crowned sparrow. Finally, we observed stronger FFRs in woodland species when tones were broadcast with the next higher harmonic in the complex. Thus, species such as nuthatches that have songs with strong harmonics may process these sounds using enhanced spectral processing instead of enhanced amplitude-envelope processing. The results suggest coevolution between signal design and temporal processing of complex signals and underscore the need to study auditory processing with a diversity of signals.

  11. Dissociated lateralization of transient and sustained blood oxygen level-dependent signal components in human primary auditory cortex.

    PubMed

    Lehmann, Christoph; Herdener, Marcus; Schneider, Peter; Federspiel, Andrea; Bach, Dominik R; Esposito, Fabrizio; di Salle, Francesco; Scheffler, Klaus; Kretz, Robert; Dierks, Thomas; Seifritz, Erich

    2007-02-15

    Among other auditory operations, the analysis of different sound levels received at both ears is fundamental for the localization of a sound source. These so-called interaural level differences, in animals, are coded by excitatory-inhibitory neurons yielding asymmetric hemispheric activity patterns with acoustic stimuli having maximal interaural level differences. In human auditory cortex, the temporal blood oxygen level-dependent (BOLD) response to auditory inputs, as measured by functional magnetic resonance imaging (fMRI), consists of at least two independent components: an initial transient and a subsequent sustained signal, which, on a different time scale, are consistent with electrophysiological human and animal response patterns. However, their specific functional role remains unclear. Animal studies suggest these temporal components being based on different neural networks and having specific roles in representing the external acoustic environment. Here we hypothesized that the transient and sustained response constituents are differentially involved in coding interaural level differences and therefore play different roles in spatial information processing. Healthy subjects underwent monaural and binaural acoustic stimulation and BOLD responses were measured using high signal-to-noise-ratio fMRI. In the anatomically segmented Heschl's gyrus the transient response was bilaterally balanced, independent of the side of stimulation, while in opposite the sustained response was contralateralized. This dissociation suggests a differential role at these two independent temporal response components, with an initial bilateral transient signal subserving rapid sound detection and a subsequent lateralized sustained signal subserving detailed sound characterization.

  12. Auditory-visual integration of emotional signals in a virtual environment for cynophobia.

    PubMed

    Taffou, Marine; Chapoulie, Emmanuelle; David, Adrien; Guerchouche, Rachid; Drettakis, George; Viaud-Delmon, Isabelle

    2012-01-01

    Cynophobia (dog phobia) has both visual and auditory relevant components. In order to investigate the efficacy of virtual reality (VR) exposure-based treatment for cynophobia, we studied the efficiency of auditory-visual environments in generating presence and emotion. We conducted an evaluation test with healthy participants sensitive to cynophobia in order to assess the capacity of auditory-visual virtual environments (VE) to generate fear reactions. Our application involves both high fidelity visual stimulation displayed in an immersive space and 3D sound. This specificity enables us to present and spatially manipulate fearful stimuli in the auditory modality, the visual modality and both. Our specific presentation of animated dog stimuli creates an environment that is highly arousing, suggesting that VR is a promising tool for cynophobia treatment and that manipulating auditory-visual integration might provide a way to modulate affect.

  13. Complexin-I is required for high-fidelity transmission at the endbulb of Held auditory synapse.

    PubMed

    Strenzke, Nicola; Chanda, Soham; Kopp-Scheinpflug, Cornelia; Khimich, Darina; Reim, Kerstin; Bulankina, Anna V; Neef, Andreas; Wolf, Fred; Brose, Nils; Xu-Friedman, Matthew A; Moser, Tobias

    2009-06-24

    Complexins (CPXs I-IV) presumably act as regulators of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, but their function in the intact mammalian nervous system is not well established. Here, we explored the role of CPXs in the mouse auditory system. Hearing was impaired in CPX I knock-out mice but normal in knock-out mice for CPXs II, III, IV, and III/IV as measured by auditory brainstem responses. Complexins were not detectable in cochlear hair cells but CPX I was expressed in spiral ganglion neurons (SGNs) that give rise to the auditory nerve. Ca(2+)-dependent exocytosis of inner hair cells and sound encoding by SGNs were unaffected in CPX I knock-out mice. In the absence of CPX I, the resting release probability in the endbulb of Held synapses of the auditory nerve fibers with bushy cells in the cochlear nucleus was reduced. As predicted by computational modeling, bushy cells had decreased spike rates at sound onset as well as longer and more variable first spike latencies explaining the abnormal auditory brainstem responses. In addition, we found synaptic transmission to outlast the stimulus at many endbulb of Held synapses in vitro and in vivo, suggesting impaired synchronization of release to stimulus offset. Although sound encoding in the cochlea proceeds in the absence of complexins, CPX I is required for faithful processing of sound onset and offset in the cochlear nucleus.

  14. Differential signaling to subplate neurons by spatially specific silent synapses in developing auditory cortex.

    PubMed

    Meng, Xiangying; Kao, Joseph P Y; Kanold, Patrick O

    2014-06-25

    Subplate neurons (SPNs) form one of the earliest maturing circuits in the cerebral cortex and are crucial to cortical development. In addition to thalamic inputs, subsets of SPNs receive excitatory AMPAR-mediated inputs from the developing cortical plate in the second postnatal week. Functionally silent (non-AMPAR-mediated) excitatory synapses exist in several systems during development, and the existence of such inputs can precede the appearance of AMPAR-mediated synapses. Because SPNs receive inputs from presynaptic cells in different cortical layers, we investigated whether AMPAR-mediated and silent synapses might originate in different layers. We used laser-scanning photostimulation in acute thalamocortical slices of mouse auditory cortex during the first 2 postnatal weeks to study the spatial origin of silent synapses onto SPNs. We find that silent synapses from the cortical plate are present on SPNs and that they originate from different cortical locations than functional (AMPAR-mediated) synapses. Moreover, we find that SPNs can be categorized based on the spatial pattern of silent and AMPAR-mediated connections. Because SPNs can be activated at young ages by thalamic inputs, distinct populations of cortical neurons at young ages have the ability to signal to SPNs depending on the activation state of SPNs. Because during development intracortical circuits are spontaneously active, our results suggest that SPNs might integrate ascending input from the thalamus with spontaneously generated cortical activity patterns. Together, our results suggest that SPNs are an integral part of the developing intracortical circuitry and thereby can sculpt thalamocortical connections.

  15. Auditory language comprehension of temporally reversed speech signals in native and non-native speakers.

    PubMed

    Kiss, Miklos; Cristescu, Tamara; Fink, Martina; Wittmann, Marc

    2008-01-01

    Neuropsychological studies in brain-injured patients with aphasia and children with specific language-learning deficits have shown the dependence of language comprehension on auditory processing abilities, i.e. the detection of temporal order. An impairment of temporal-order perception can be simulated by time reversing segments of the speech signal. In our study, we investigated how different lengths of time-reversed segments in speech influenced comprehension in ten native German speakers and ten participants who had acquired German as a second language. Results show that native speakers were still able to understand the distorted speech at segment lengths of 50 ms, whereas non-native speakers only could identify sentences with reversed intervals of 32 ms duration. These differences in performance can be interpreted by different levels of semantic and lexical proficiency. Our method of temporally-distorted speech offers a new approach to assess language skills that indirectly taps into lexical and semantic competence of non-native speakers.

  16. To modulate and be modulated: estrogenic influences on auditory processing of communication signals within a socio-neuro-endocrine framework.

    PubMed

    Yoder, Kathleen M; Vicario, David S

    2012-02-01

    Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1) Local estradiol action within an auditory area is necessary for socially relevant sounds to induce normal physiological responses in the brains of both sexes; 2) These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3) Estradiol action within the auditory forebrain enables behavioral discrimination among socially relevant sounds in males; and 4) Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors.

  17. Operator Auditory Perception and Spectral Quantification of Umbilical Artery Doppler Ultrasound Signals

    PubMed Central

    Thuring, Ann; Brännström, K. Jonas; Ewerlöf, Maria; Hernandez-Andrade, Edgar; Ley, David; Lingman, Göran; Liuba, Karina; Maršál, Karel; Jansson, Tomas

    2013-01-01

    Objective An experienced sonographer can by listening to the Doppler audio signals perceive various timbres that distinguish different types of umbilical artery flow despite an unchanged pulsatility index (PI). Our aim was to develop an objective measure of the Doppler audio signals recorded from fetoplacental circulation in a sheep model. Methods Various degrees of pathological flow velocity waveforms in the umbilical artery, similar to those in human complicated pregnancies, were induced by microsphere embolization of the placental bed (embolization model, 7 lamb fetuses, 370 Doppler recordings) or by fetal hemodilution (anemia model, 4 lamb fetuses, 184 recordings). A subjective 11-step operator auditory scale (OAS) was related to conventional Doppler parameters, PI and time average mean velocity (TAM), and to sound frequency analysis of Doppler signals (sound frequency with the maximum energy content [MAXpeak] and frequency band at maximum level minus 15 dB [MAXpeak-15 dB] over several heart cycles). Results We found a negative correlation between the OAS and PI: median Rho −0.73 (range −0.35– −0.94) and −0.68 (range −0.57– −0.78) in the two lamb models, respectively. There was a positive correlation between OAS and TAM in both models: median Rho 0.80 (range 0.58–0.95) and 0.90 (range 0.78–0.95), respectively. A strong correlation was found between TAM and the results of sound spectrum analysis; in the embolization model the median r was 0.91 (range 0.88–0.97) for MAXpeak and 0.91 (range 0.82–0.98) for MAXpeak-15 dB. In the anemia model, the corresponding values were 0.92 (range 0.78–0.96) and 0.96 (range 0.89–0.98), respectively. Conclusion Audio-spectrum analysis reflects the subjective perception of Doppler sound signals in the umbilical artery and has a strong correlation to TAM-velocity. This information might be of importance for clinical management of complicated pregnancies as an addition to conventional Doppler parameters

  18. 29 CFR 1926.1419 - Signals-general requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 8 2014-07-01 2014-07-01 false Signals-general requirements. 1926.1419 Section 1926.1419... Construction § 1926.1419 Signals—general requirements. (a) A signal person must be provided in each of the... person handling the load determines that it is necessary. (b) Types of signals. Signals to operators must...

  19. 29 CFR 1926.1419 - Signals-general requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 8 2011-07-01 2011-07-01 false Signals-general requirements. 1926.1419 Section 1926.1419... Construction § 1926.1419 Signals—general requirements. (a) A signal person must be provided in each of the... person handling the load determines that it is necessary. (b) Types of signals. Signals to operators must...

  20. Protein synthesis in the amygdala, but not the auditory thalamus, is required for consolidation of Pavlovian fear conditioning in rats.

    PubMed

    Maren, Stephen; Ferrario, Carrie R; Corcoran, Kevin A; Desmond, Timothy J; Frey, Kirk A

    2003-12-01

    The amygdala is an essential neural substrate for Pavlovian fear conditioning. Nevertheless, long-term synaptic plasticity in amygdaloid afferents, such as the auditory thalamus, may contribute to the formation of fear memories. We therefore compared the influence of protein synthesis inhibition in the amygdala and the auditory thalamus on the consolidation of Pavlovian fear conditioning in Long-Evans rats. Rats received three tone-footshock trials in a novel conditioning chamber. Immediately after fear conditioning, rats were infused intra-cranially with the protein synthesis inhibitor, anisomycin. Conditional fear to the tone and conditioning context was assessed by measuring freezing behaviour in separate retention tests conducted at least 24 h following conditioning. Post-training infusion of anisomycin into the amygdala impaired conditional freezing to both the auditory and contextual stimuli associated with footshock. In contrast, intra-thalamic infusions of anisomycin or a broad-spectrum protein kinase inhibitor [1-(5'-isoquinolinesulphonyl)-2-methylpiperazine, H7] did not affect conditional freezing during the retention tests. Pre-training intra-thalamic infusion of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (APV), which blocks synaptic transmission in the auditory thalamus, produced a selective deficit in the acquisition of auditory fear conditioning. Autoradiographic assays of cerebral [14C]-leucine incorporation revealed similar levels of protein synthesis inhibition in the amygdala and thalamus following intra-cranial anisomycin infusions. These results reveal that the establishment of long-term fear memories requires protein synthesis in the amygdala, but not the thalamus, after auditory fear conditioning. Forms of synaptic plasticity that depend on protein synthesis, such as long-term potentiation, are likely candidates for the encoding and long-term storage of fear memories in the amygdala.

  1. L-type Calcium Channel Cav1.2 Is Required for Maintenance of Auditory Brainstem Nuclei*

    PubMed Central

    Ebbers, Lena; Satheesh, Somisetty V.; Janz, Katrin; Rüttiger, Lukas; Blosa, Maren; Hofmann, Franz; Morawski, Markus; Griesemer, Désirée; Knipper, Marlies; Friauf, Eckhard; Nothwang, Hans Gerd

    2015-01-01

    Cav1.2 and Cav1.3 are the major L-type voltage-gated Ca2+ channels in the CNS. Yet, their individual in vivo functions are largely unknown. Both channel subunits are expressed in the auditory brainstem, where Cav1.3 is essential for proper maturation. Here, we investigated the role of Cav1.2 by targeted deletion in the mouse embryonic auditory brainstem. Similar to Cav1.3, loss of Cav1.2 resulted in a significant decrease in the volume and cell number of auditory nuclei. Contrary to the deletion of Cav1.3, the action potentials of lateral superior olive (LSO) neurons were narrower compared with controls, whereas the firing behavior and neurotransmission appeared unchanged. Furthermore, auditory brainstem responses were nearly normal in mice lacking Cav1.2. Perineuronal nets were also unaffected. The medial nucleus of the trapezoid body underwent a rapid cell loss between postnatal days P0 and P4, shortly after circuit formation. Phosphorylated cAMP response element-binding protein (CREB), nuclear NFATc4, and the expression levels of p75NTR, Fas, and FasL did not correlate with cell death. These data demonstrate for the first time that both Cav1.2 and Cav1.3 are necessary for neuronal survival but are differentially required for the biophysical properties of neurons. Thus, they perform common as well as distinct functions in the same tissue. PMID:26242732

  2. The contribution of auditory temporal processing to the separation of competing speech signals in listeners with normal hearing

    NASA Astrophysics Data System (ADS)

    Adam, Trudy J.; Pichora-Fuller, Kathy

    2002-05-01

    The hallmark of auditory function in aging adults is difficulty listening in a background of competing talkers, even when hearing sensitivity in quiet is good. Age-related physiological changes may contribute by introducing small timing errors (jitter) to the neural representation of sound, compromising the fidelity of the signal's fine temporal structure. This may preclude the association of spectral features to form an accurate percept of one complex stimulus, distinct from competing sounds. For simple voiced speech (vowels), the separation of two competing stimuli can be achieved on the basis of their respective harmonic (temporal) structures. Fundamental frequency (F0) differences in competing stimuli facilitate their segregation. This benefit was hypothesized to rely on the adequate temporal representation of the speech signal(s). Auditory aging was simulated via the desynchronization (~0.25-ms jitter) of the spectral bands of synthesized vowels. The perceptual benefit of F0 difference for the identification of concurrent vowel pairs was examined for intact and jittered vowels in young adults with normal hearing thresholds. Results suggest a role for reduced signal fidelity in the perceptual difficulties encountered in noisy everyday environments by aging listeners. [Work generously supported by the Michael Smith Foundation for Health Research.

  3. 49 CFR 236.205 - Signal control circuits; requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Signal control circuits; requirements. 236.205... Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so... fouling point derail equipped with switch circuit controller is not in derailing position, (d) When a...

  4. 49 CFR 236.205 - Signal control circuits; requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Signal control circuits; requirements. 236.205... Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so... fouling point derail equipped with switch circuit controller is not in derailing position, (d) When a...

  5. 49 CFR 236.205 - Signal control circuits; requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Signal control circuits; requirements. 236.205... Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so... fouling point derail equipped with switch circuit controller is not in derailing position, (d) When a...

  6. 49 CFR 236.205 - Signal control circuits; requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Signal control circuits; requirements. 236.205... Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so... fouling point derail equipped with switch circuit controller is not in derailing position, (d) When a...

  7. 49 CFR 236.205 - Signal control circuits; requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Signal control circuits; requirements. 236.205... Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so... fouling point derail equipped with switch circuit controller is not in derailing position, (d) When a...

  8. 49 CFR 236.14 - Spring switch signal protection; requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block...

  9. 49 CFR 236.14 - Spring switch signal protection; requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block...

  10. 49 CFR 236.14 - Spring switch signal protection; requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block...

  11. 49 CFR 236.14 - Spring switch signal protection; requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block...

  12. 49 CFR 236.14 - Spring switch signal protection; requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Spring switch signal protection; requirements. 236... Rules and Instructions: All Systems General § 236.14 Spring switch signal protection; requirements. (a... track signaled for movements in only one direction through a spring switch in automatic block...

  13. Engineered deafness reveals that mouse courtship vocalizations do not require auditory experience.

    PubMed

    Mahrt, Elena J; Perkel, David J; Tong, Ling; Rubel, Edwin W; Portfors, Christine V

    2013-03-27

    Auditory experience during development is necessary for normal language acquisition in humans. Although songbirds, some cetaceans, and maybe bats may also be vocal learners, vocal learning has yet to be well established for a laboratory mammal. Mice are potentially an excellent model organism for studying mechanisms underlying vocal communication. Mice vocalize in different social contexts, yet whether they learn their vocalizations remains unresolved. To address this question, we compared ultrasonic courtship vocalizations emitted by chronically deaf and normal hearing adult male mice. We deafened CBA/CaJ male mice, engineered to express diphtheria toxin (DT) receptors in hair cells, by systemic injection of DT at postnatal day 2 (P2). By P9, almost all inner hair cells were absent and by P16 all inner and outer hair cells were absent in DTR mice. These mice did not show any auditory brainstem responses as adults. Wild-type littermates, also treated with DT at P2, had normal hair cells and normal auditory brainstem responses. We compared the temporal structure of vocalization bouts, the types of vocalizations, the patterns of syllables, and the acoustic features of each syllable type emitted by hearing and deaf males in the presence of a female. We found that almost all of the vocalization features we examined were similar in hearing and deaf animals. These findings indicate that mice do not need auditory experience during development to produce normal ultrasonic vocalizations in adulthood. We conclude that mouse courtship vocalizations are not acquired through auditory feedback-dependent learning.

  14. Adaptive categorization of sound frequency does not require the auditory cortex in rats.

    PubMed

    Gimenez, Tyler L; Lorenc, Maja; Jaramillo, Santiago

    2015-08-01

    A defining feature of adaptive behavior is our ability to change the way we interpret sensory stimuli depending on context. Rapid adaptation in behavior has been attributed to frontal cortical circuits, but it is not clear if sensory cortexes also play an essential role in such tasks. In this study we tested whether the auditory cortex was necessary for rapid adaptation in the interpretation of sounds. We used a two-alternative choice sound-categorization task for rats in which the boundary that separated two acoustic categories changed several times within a behavioral session. These shifts in the boundary resulted in changes in the rewarded action for a subset of stimuli. We found that extensive lesions of the auditory cortex did not impair the ability of rats to switch between categorization contingencies and sound discrimination performance was minimally impaired. Similar results were obtained after reversible inactivation of the auditory cortex with muscimol. In contrast, lesions of the auditory thalamus largely impaired discrimination performance and, as a result, the ability to modify behavior across contingencies. Thalamic lesions did not impair performance of a visual discrimination task, indicating that the effects were specific to audition and not to motor preparation or execution. These results suggest that subcortical outputs of the auditory thalamus can mediate rapid adaptation in the interpretation of sounds. Copyright © 2015 the American Physiological Society.

  15. Auditory Responses in the Barn Owl's Nucleus Laminaris to Clicks: Impulse Response and Signal Analysis of Neurophonic Potential

    PubMed Central

    Wagner, Hermann; Brill, Sandra; Kempter, Richard; Carr, Catherine E.

    2009-01-01

    We used acoustic clicks to study the impulse response of the neurophonic potential in the barn owl's nucleus laminaris. Clicks evoked a complex oscillatory neural response with a component that reflected the best frequency measured with tonal stimuli. The envelope of this component was obtained from the analytic signal created using the Hilbert transform. The time courses of the envelope and carrier waveforms were characterized by fitting them with filters. The envelope was better fitted with a Gaussian than with the envelope of a gamma-tone function. The carrier was better fitted with a frequency glide than with a constant instantaneous frequency. The change of the instantaneous frequency with time was better fitted with a linear fit than with a saturating nonlinearity. Frequency glides had not been observed in the bird's auditory system before. The glides were similar to those observed in the mammalian auditory nerve. Response amplitude, group delay, frequency, and phase depended in a systematic way on click level. In most cases, response amplitude decreased linearly as stimulus level decreased, while group delay, phase, and frequency increased linearly as level decreased. Thus the impulse response of the neurophonic potential in the nucleus laminaris of barn owls reflects many characteristics also observed in responses of the basilar membrane and auditory nerve in mammals. PMID:19535487

  16. Event related aspects of somatosensory and auditory evoked potentials: noise or signals?

    PubMed

    Stowell, H

    1985-05-01

    The so-called Vertex Potential (VP) of human scalp-conducted and event related brain potential (ERBP), which occur as a slow and often large, biphasic sinusoid within the 100-400 msec time segment after transient stimulation in the three main sensory modalities, are the longest researched of all human evoked potential (EP) phenomena. Its variable amplitude has been directly correlated, in experiments expressly tailored for the purpose, with input/output variables such as the rate of acceleration of given stimulus parameters from a state of relative rest (RM function), interstimulus interval (ISI), stimulus intensity, skin potential and resistance changes (SPR and SRR), the peripheral electroneurogram (ENG), and experimentally isolated C-fiber afference; and with neuropsychological variables such as attention or vigilance, visual acuity, response time, subjective stimulus probability or expectancy, acute pain of both fast and slow kinds, intelligence quotient (IQ), and psychometric personality scores (e.g., extraversion versus introversion and neuroticism versus normality). Unfortunately, the cerebral, neural origins of the VP, if any, are unknown; it is reported as usually absent from cortex-surface EP in those primates and mammals hitherto studied, and also from human extracranial event related magnetic fields of the brain (ERMFb) insofar as these reveal only superficial tangential sources; but a possible analog has been recorded from deep subcortical electrodes during human neurosurgery. In view of the increasing published range and quantity of direct correlates of VP amplitude, and of the scarcity of data about its neuroanatomy and neurophysiology, it seemed a good idea to do some rudimentary signal analysis. Preliminary results from five subjects confirm earlier data: The VP of somatosensory (SEP) and auditory (AEP) evoked potentials, as obtained by scalp-conductance and either averaged or single-epoch, can be resolved into inconsistently stimulus synchronized

  17. Verbal Recall of Auditory and Visual Signals by Normal and Deficient Reading Children.

    ERIC Educational Resources Information Center

    Levine, Maureen Julianne

    Verbal recall of bisensory memory tasks was compared among 48 9- to 12-year old boys in three groups: normal readers, primary deficit readers, and secondary deficit readers. Auditory and visual stimulus pairs composed of digits, which incorporated variations of intersensory and intrasensory conditions were administered to Ss through a Bell and…

  18. Retrosplenial Cortex Is Required for the Retrieval of Remote Memory for Auditory Cues

    ERIC Educational Resources Information Center

    Todd, Travis P.; Mehlman, Max L.; Keene, Christopher S.; DeAngeli, Nicole E.; Bucci, David J.

    2016-01-01

    The retrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo-spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of…

  19. Retrosplenial Cortex Is Required for the Retrieval of Remote Memory for Auditory Cues

    ERIC Educational Resources Information Center

    Todd, Travis P.; Mehlman, Max L.; Keene, Christopher S.; DeAngeli, Nicole E.; Bucci, David J.

    2016-01-01

    The retrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo-spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of…

  20. [The role of the ventral nucleus of the lateral lemniscus in sound signal processing and auditory ascending transmission].

    PubMed

    Liu, Hui-Hua; Luo, Feng; Wang, Xin

    2014-06-25

    The ventral nucleus of the lateral lemniscus (VNLL) is an important nucleus in the central auditory pathway which connects the lower brainstem and the midbrain inferior colliculus (IC). Previous studies have demonstrated that neurons in the VNLL could respond to sound signal parameters. Frequency tuning curves (FTCs) of VNLL neurons are generally wider than FTCs of IC neurons, suggesting that the VNLL does not enhance abilities of frequency discrimination and coding. Two types of rate-intensity functions (RIFs) are found in the VNLL: monotonic and non-monotonic RIFs. Intensity-tuning of VNLL neurons are affected by the temporal firing patterns during processing and encoding intensity. There are multiple temporal firing patterns in VNLL neurons. Onset pattern has a precise timing characteristic which is well suited to encode temporal features of stimuli, and also very important to animal behavior including bat's echolocation. The VNLL accepts inputs from lower nuclei, uploads glycine inhibitory outputs to IC, and modulates response characteristics generating and acoustic signal processing of IC neurons. Recent research suggests that fast inhibitory projection from the VNLL may delay the first spike latency of IC neurons, and the delayed inhibitory projection from the VNLL may mediate the temporal firing patterns of IC neurons. But how inhibitory inputs from the VNLL integrate in IC, and how inhibitory inputs from the VNLL enhance the ability of detecting sound signal of IC neurons are not very clear and need more direct evidence at the level of neurons. These questions will help further understand the role of upload during IC processes acoustic signal, which are our research target in the future. This article reviews the current literature regarding the roles of the VNLL in sound signal processing and the auditory ascending transmission, including advances in the relevant research in our laboratory.

  1. 46 CFR 161.013-7 - Signal requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 6 2012-10-01 2012-10-01 false Signal requirements. 161.013-7 Section 161.013-7...: SPECIFICATIONS AND APPROVAL ELECTRICAL EQUIPMENT Electric Distress Light for Boats § 161.013-7 Signal... each S-O-S signal must have a duration of 3 seconds. (b) The flash characteristics described in...

  2. 46 CFR 161.013-7 - Signal requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Signal requirements. 161.013-7 Section 161.013-7...: SPECIFICATIONS AND APPROVAL ELECTRICAL EQUIPMENT Electric Distress Light for Boats § 161.013-7 Signal... each S-O-S signal must have a duration of 3 seconds. (b) The flash characteristics described in...

  3. Does common spatial origin promote the auditory grouping of temporally separated signal elements in grey treefrogs?

    PubMed

    Bee, Mark A; Riemersma, Kasen K

    2008-09-01

    'Sequential integration' represents a form of auditory grouping in which temporally separated sounds produced by the same source are perceptually bound together over time into a coherent 'auditory stream'. In humans, sequential integration plays important roles in music and speech perception. In this study of the grey treefrog (Hyla chrysoscelis), we took advantage of female selectivity for advertisement calls with conspecific pulse rates to investigate common spatial location as a cue for sequential integration. We presented females with two temporally interleaved pulse sequences with pulse rates of 25 pulses/s, which is half the conspecific pulse rate and more similar to that of H. versicolor, a syntopically breeding heterospecific. We tested the hypothesis that common spatial origin between the two pulse sequences would promote their integration into a coherent auditory stream with an attractive conspecific pulse rate. As the spatial separation between the speakers broadcasting the interleaved pulse sequences decreased from 180° to 0°, more females responded and females exhibited shorter response latencies and travelled shorter distances en route to a speaker. However, even in the 180° condition, most females (74%) still responded. Detailed video analyses revealed no evidence to suggest that patterns of female phonotaxis resulted from impaired abilities to localize sound sources in the spatially separated conditions. Together, our results suggest that females were fairly permissive of spatial incoherence between the interleaved pulses sequences and that common spatial origin may be only a relatively weak cue for sequential integration in grey treefrogs.

  4. Does common spatial origin promote the auditory grouping of temporally separated signal elements in grey treefrogs?

    PubMed Central

    Bee, Mark A.; Riemersma, Kasen K.

    2008-01-01

    ‘Sequential integration’ represents a form of auditory grouping in which temporally separated sounds produced by the same source are perceptually bound together over time into a coherent ‘auditory stream’. In humans, sequential integration plays important roles in music and speech perception. In this study of the grey treefrog (Hyla chrysoscelis), we took advantage of female selectivity for advertisement calls with conspecific pulse rates to investigate common spatial location as a cue for sequential integration. We presented females with two temporally interleaved pulse sequences with pulse rates of 25 pulses/s, which is half the conspecific pulse rate and more similar to that of H. versicolor, a syntopically breeding heterospecific. We tested the hypothesis that common spatial origin between the two pulse sequences would promote their integration into a coherent auditory stream with an attractive conspecific pulse rate. As the spatial separation between the speakers broadcasting the interleaved pulse sequences decreased from 180° to 0°, more females responded and females exhibited shorter response latencies and travelled shorter distances en route to a speaker. However, even in the 180° condition, most females (74%) still responded. Detailed video analyses revealed no evidence to suggest that patterns of female phonotaxis resulted from impaired abilities to localize sound sources in the spatially separated conditions. Together, our results suggest that females were fairly permissive of spatial incoherence between the interleaved pulses sequences and that common spatial origin may be only a relatively weak cue for sequential integration in grey treefrogs. PMID:19727419

  5. 46 CFR 161.013-7 - Signal requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: SPECIFICATIONS AND APPROVAL ELECTRICAL EQUIPMENT Electric Distress Light for Boats § 161.013-7 Signal requirements. (a) An electric light must have a flash characteristic of the International Morse Code for S-O-S... 46 Shipping 6 2010-10-01 2010-10-01 false Signal requirements. 161.013-7 Section...

  6. 14 CFR 171.311 - Signal format requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... processing. The signal format must meet the following minimum requirements: (a) Frequency assignment. The... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Signal format requirements. 171.311 Section...) NAVIGATIONAL FACILITIES NON-FEDERAL NAVIGATION FACILITIES Microwave Landing System (MLS) § 171.311...

  7. 14 CFR 171.311 - Signal format requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... processing. The signal format must meet the following minimum requirements: (a) Frequency assignment. The... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Signal format requirements. 171.311 Section...) NAVIGATIONAL FACILITIES NON-FEDERAL NAVIGATION FACILITIES Microwave Landing System (MLS) § 171.311...

  8. 29 CFR 1926.1421 - Signals-voice signals-additional requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 8 2011-07-01 2011-07-01 false Signals-voice signals-additional requirements. 1926.1421... Derricks in Construction § 1926.1421 Signals—voice signals—additional requirements. (a) Prior to beginning operations, the operator, signal person and lift director (if there is one), must contact each other and...

  9. 29 CFR 1926.1421 - Signals-voice signals-additional requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 8 2012-07-01 2012-07-01 false Signals-voice signals-additional requirements. 1926.1421... Derricks in Construction § 1926.1421 Signals—voice signals—additional requirements. (a) Prior to beginning operations, the operator, signal person and lift director (if there is one), must contact each other and...

  10. 29 CFR 1926.1421 - Signals-voice signals-additional requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 8 2014-07-01 2014-07-01 false Signals-voice signals-additional requirements. 1926.1421... Derricks in Construction § 1926.1421 Signals—voice signals—additional requirements. (a) Prior to beginning operations, the operator, signal person and lift director (if there is one), must contact each other and...

  11. 29 CFR 1926.1421 - Signals-voice signals-additional requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 8 2013-07-01 2013-07-01 false Signals-voice signals-additional requirements. 1926.1421... Derricks in Construction § 1926.1421 Signals—voice signals—additional requirements. (a) Prior to beginning operations, the operator, signal person and lift director (if there is one), must contact each other and...

  12. Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T.

    PubMed

    Casciaro, Sergio; Bianco, Roberto; Distante, Alessandro

    2008-11-01

    Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (P<10(-7)) and area (P<10(-8)) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties.

  13. Auditory, visual, and auditory-visual processing performance in typically developing children: modality independence versus dependence.

    PubMed

    Pillai, Roshni; Yathiraj, Asha

    2015-02-01

    The study was carried out to determine whether cross-modal interactions occur during processing of auditory and/or visual signals that require separation/closure, integration, and duration pattern perception in typically developing children. Thirty typically developing children were evaluated on three auditory processing tests (speech-in-noise test in Indian-English, dichotic-consonant vowel test, and duration pattern test) that tapped separation/closure, integration and duration pattern perception. The children were also evaluated on the visual and auditory-visual analogues of the auditory tests. Differences in modality were found in each of the processes that were tested. The performance when the auditory and visual modalities were tested simultaneously was significantly higher than the auditory or visual modality for tests that involved separation/closure and integration. In contrast, scores on the analogous auditory-visual duration pattern test were significantly higher than the auditory test but not the visual analogous test. Further, the scores of the auditory modality were significantly poorer than the visual modality for separation/closure and duration patterning but not for integration. Findings of the study indicate that performance on higher level processing varies depending on the modality that is assessed and supports the presence of cross-modality interactions.

  14. Auditory object salience: human cortical processing of non-biological action sounds and their acoustic signal attributes.

    PubMed

    Lewis, James W; Talkington, William J; Tallaksen, Katherine C; Frum, Chris A

    2012-01-01

    Whether viewed or heard, an object in action can be segmented as a distinct salient event based on a number of different sensory cues. In the visual system, several low-level attributes of an image are processed along parallel hierarchies, involving intermediate stages wherein gross-level object form and/or motion features are extracted prior to stages that show greater specificity for different object categories (e.g., people, buildings, or tools). In the auditory system, though relying on a rather different set of low-level signal attributes, meaningful real-world acoustic events and "auditory objects" can also be readily distinguished from background scenes. However, the nature of the acoustic signal attributes or gross-level perceptual features that may be explicitly processed along intermediate cortical processing stages remain poorly understood. Examining mechanical and environmental action sounds, representing two distinct non-biological categories of action sources, we had participants assess the degree to which each sound was perceived as object-like versus scene-like. We re-analyzed data from two of our earlier functional magnetic resonance imaging (fMRI) task paradigms (Engel et al., 2009) and found that scene-like action sounds preferentially led to activation along several midline cortical structures, but with strong dependence on listening task demands. In contrast, bilateral foci along the superior temporal gyri (STG) showed parametrically increasing activation to action sounds rated as more "object-like," independent of sound category or task demands. Moreover, these STG regions also showed parametric sensitivity to spectral structure variations (SSVs) of the action sounds-a quantitative measure of change in entropy of the acoustic signals over time-and the right STG additionally showed parametric sensitivity to measures of mean entropy and harmonic content of the environmental sounds. Analogous to the visual system, intermediate stages of the

  15. The autophagy pathway maintained signaling crosstalk with the Keap1-Nrf2 system through p62 in auditory cells under oxidative stress.

    PubMed

    Hayashi, Ken; Dan, Katsuaki; Goto, Fumiyuki; Tshuchihashi, Nana; Nomura, Yasuyuki; Fujioka, Masato; Kanzaki, Sho; Ogawa, Kaoru

    2015-02-01

    The main purposes of our study were to consider the effect of autophagy on auditory cells under oxidative stress, and the function of possible crosstalk among p62, Keap1 and Nrf2 in autophagy-deficient auditory cells. First, we described how cell death was induced in auditory cell line (HEI-OC1) exposed to H2O2. We found that the decision for the cell death of auditory cells under oxidative stress depends on the balance between autophagy and necrosis due to ATP depletion, and autophagy plays a cytoprotective function in oxidative stress-induced necrosis. Our data clearly suggested that autophagy was a cell survival mechanism in H2O2-induced cell death, based on the observation that suppression of autophagy by knockdown of Atg7 sensitized, whereas activation of autophagy by rapamycin protected against H2O2-induced cell death. Next, our results regarding the relationship among p62, Nrf2 and Keap1 by siRNA paradoxically showed that p62 creates a positive feedback loop in the Keap1/Nrf2 pathway. Autophagy impaired by Atg7 knockdown degrades Keap1 in a p62-dependent manner, whereas Nrf2 is activated. As a result, the cell death induced by H2O2 was promoted in auditory cells. Taken together, these results suggested that the autophagy pathway maintained signaling crosstalk with the Keap1-Nrf2 system through p62 in auditory cells under oxidative stress.

  16. Habituation of Auditory Steady State Responses Evoked by Amplitude-Modulated Acoustic Signals in Rats

    PubMed Central

    Prado-Gutierrez, Pavel; Castro-Fariñas, Anisleidy; Morgado-Rodriguez, Lisbet; Velarde-Reyes, Ernesto; Martínez, Agustín D.; Martínez-Montes, Eduardo

    2015-01-01

    Generation of the auditory steady state responses (ASSR) is commonly explained by the linear combination of random background noise activity and the stationary response. Based on this model, the decrease of amplitude that occurs over the sequential averaging of epochs of the raw data has been exclusively linked to the cancelation of noise. Nevertheless, this behavior might also reflect the non-stationary response of the ASSR generators. We tested this hypothesis by characterizing the ASSR time course in rats with different auditory maturational stages. ASSR were evoked by 8-kHz tones of different supra-threshold intensities, modulated in amplitude at 115 Hz. Results show that the ASSR amplitude habituated to the sustained stimulation and that dishabituation occurred when deviant stimuli were presented. ASSR habituation increased as animals became adults, suggesting that the ability to filter acoustic stimuli with no-relevant temporal information increased with age. Results are discussed in terms of the current model of the ASSR generation and analysis procedures. They might have implications for audiometric tests designed to assess hearing in subjects who cannot provide reliable results in the psychophysical trials. PMID:26557360

  17. Selective attention and the auditory vertex potential. 2: Effects of signal intensity and masking noise

    NASA Technical Reports Server (NTRS)

    Schwent, V. L.; Hillyard, S. A.; Galambos, R.

    1975-01-01

    A randomized sequence of tone bursts was delivered to subjects at short inter-stimulus intervals with the tones originating from one of three spatially and frequency specific channels. The subject's task was to count the tones in one of the three channels at a time, ignoring the other two, and press a button after each tenth tone. In different conditions, tones were given at high and low intensities and with or without a background white noise to mask the tones. The N sub 1 component of the auditory vertex potential was found to be larger in response to attended channel tones in relation to unattended tones. This selective enhancement of N sub 1 was minimal for loud tones presented without noise and increased markedly for the lower tone intensity and in noise added conditions.

  18. Auditory scene analysis by echolocation in bats.

    PubMed

    Moss, C F; Surlykke, A

    2001-10-01

    Echolocating bats transmit ultrasonic vocalizations and use information contained in the reflected sounds to analyze the auditory scene. Auditory scene analysis, a phenomenon that applies broadly to all hearing vertebrates, involves the grouping and segregation of sounds to perceptually organize information about auditory objects. The perceptual organization of sound is influenced by the spectral and temporal characteristics of acoustic signals. In the case of the echolocating bat, its active control over the timing, duration, intensity, and bandwidth of sonar transmissions directly impacts its perception of the auditory objects that comprise the scene. Here, data are presented from perceptual experiments, laboratory insect capture studies, and field recordings of sonar behavior of different bat species, to illustrate principles of importance to auditory scene analysis by echolocation in bats. In the perceptual experiments, FM bats (Eptesicus fuscus) learned to discriminate between systematic and random delay sequences in echo playback sets. The results of these experiments demonstrate that the FM bat can assemble information about echo delay changes over time, a requirement for the analysis of a dynamic auditory scene. Laboratory insect capture experiments examined the vocal production patterns of flying E. fuscus taking tethered insects in a large room. In each trial, the bats consistently produced echolocation signal groups with a relatively stable repetition rate (within 5%). Similar temporal patterning of sonar vocalizations was also observed in the field recordings from E. fuscus, thus suggesting the importance of temporal control of vocal production for perceptually guided behavior. It is hypothesized that a stable sonar signal production rate facilitates the perceptual organization of echoes arriving from objects at different directions and distances as the bat flies through a dynamic auditory scene. Field recordings of E. fuscus, Noctilio albiventris, N

  19. Evolutionary diversification of the auditory organ sensilla in Neoconocephalus katydids (Orthoptera: Tettigoniidae) correlates with acoustic signal diversification over phylogenetic relatedness and life history.

    PubMed

    Strauß, Johannes; Alt, Joscha A; Ekschmitt, Klemens; Schul, Johannes; Lakes-Harlan, Reinhard

    2017-03-13

    Neoconocephalus Tettigoniidae are a model for the evolution of acoustic signals as male calls have diversified in temporal structure during the radiation of the genus. The call divergence and phylogeny in Neoconocephalus are established, but in tettigoniids in general, accompanying evolutionary changes in hearing organs are not studied. We investigated anatomical changes of the tympanal hearing organs during evolutionary radiation and divergence of intraspecific acoustic signals. We compared the neuroanatomy of auditory sensilla (crista acustica) from nine Neoconocephalus species for the number of auditory sensilla and the crista acustica length. These parameters were correlated to differences in temporal call features, body size, life histories, and different phylogenetic positions. By this, adaptive responses to shifting frequencies of male calls and changes in their temporal patterns can be evaluated against phylogenetic constraints and allometry. All species showed well-developed auditory sensilla, on average 32-35 between species. Crista acustica length and sensillum numbers correlated with body size, but not with phylogenetic position or life history. Statistically significant correlations existed also with specific call patterns: a higher number of auditory sensilla occurred in species with continuous calls or slow pulse rates, and a longer crista acustica occurred in species with double pulses or slow pulse rates. The auditory sensilla show significant differences between species despite their recent radiation, and morphological and ecological similarities. This indicates the responses to natural and sexual selection, including divergence of temporal and spectral signal properties. Phylogenetic constraints are unlikely to limit these changes of the auditory systems. This article is protected by copyright. All rights reserved.

  20. Signal- and Listener-Based Factors in Complex Auditory Pattern Perception

    DTIC Science & Technology

    1991-10-07

    that deals with complex signals, including speech and music . 15 References Fodor, J.A. (1983). The Modularity of Mind . MIT Press, Cambridge, Mass...patterns, including speech and music . One set of experiments explored two early stages in the perception of complex signals, using adaptation procedures...patterns, including speech and music . One set of experiments explored two early stages in the perception of complex signals, using adaptation

  1. Acoustic duetting in Drosophila virilis relies on the integration of auditory and tactile signals

    PubMed Central

    LaRue, Kelly M; Clemens, Jan; Berman, Gordon J; Murthy, Mala

    2015-01-01

    Many animal species, including insects, are capable of acoustic duetting, a complex social behavior in which males and females tightly control the rate and timing of their courtship song syllables relative to each other. The mechanisms underlying duetting remain largely unknown across model systems. Most studies of duetting focus exclusively on acoustic interactions, but the use of multisensory cues should aid in coordinating behavior between individuals. To test this hypothesis, we develop Drosophila virilis as a new model for studies of duetting. By combining sensory manipulations, quantitative behavioral assays, and statistical modeling, we show that virilis females combine precisely timed auditory and tactile cues to drive song production and duetting. Tactile cues delivered to the abdomen and genitalia play the larger role in females, as even headless females continue to coordinate song production with courting males. These data, therefore, reveal a novel, non-acoustic, mechanism for acoustic duetting. Finally, our results indicate that female-duetting circuits are not sexually differentiated, as males can also produce ‘female-like’ duets in a context-dependent manner. DOI: http://dx.doi.org/10.7554/eLife.07277.001 PMID:26046297

  2. The acquisition of mechano‐electrical transducer current adaptation in auditory hair cells requires myosin VI

    PubMed Central

    Marcotti, Walter; Corns, Laura F.; Goodyear, Richard J.; Rzadzinska, Agnieszka K.; Avraham, Karen B.; Steel, Karen P.; Richardson, Guy P.

    2016-01-01

    Key points The transduction of sound into electrical signals occurs at the hair bundles atop sensory hair cells in the cochlea, by means of mechanosensitive ion channels, the mechano‐electrical transducer (MET) channels.The MET currents decline during steady stimuli; this is termed adaptation and ensures they always work within the most sensitive part of their operating range, responding best to rapidly changing (sound) stimuli.In this study we used a mouse model (Snell's waltzer) for hereditary deafness in humans that has a mutation in the gene encoding an unconventional myosin, myosin VI, which is present in the hair bundles.We found that in the absence of myosin VI the MET current fails to acquire its characteristic adaptation as the hair bundles develop.We propose that myosin VI supports the acquisition of adaptation by removing key molecules from the hair bundle that serve a temporary, developmental role. Abstract Mutations in Myo6, the gene encoding the (F‐actin) minus end‐directed unconventional myosin, myosin VI, cause hereditary deafness in mice (Snell's waltzer) and humans. In the sensory hair cells of the cochlea, myosin VI is expressed in the cell bodies and along the stereocilia that project from the cells’ apical surface. It is required for maintaining the structural integrity of the mechanosensitive hair bundles formed by the stereocilia. In this study we investigate whether myosin VI contributes to mechano‐electrical transduction. We report that Ca2+‐dependent adaptation of the mechano‐electrical transducer (MET) current, which serves to keep the transduction apparatus operating within its most sensitive range, is absent in outer and inner hair cells from homozygous Snell's waltzer mutant mice, which fail to express myosin VI. The operating range of the MET channels is also abnormal in the mutants, resulting in the absence of a resting MET current. We found that cadherin 23, a component of the hair bundle's transient lateral links

  3. Different requirements for Wnt signaling in tongue myogenic subpopulations.

    PubMed

    Zhong, Z; Zhao, H; Mayo, J; Chai, Y

    2015-03-01

    The tongue is a muscular organ that is essential in vertebrates for important functions, such as food intake and communication. Little is known about regulation of myogenic progenitors during tongue development when compared with the limb or trunk region. In this study, we investigated the relationship between different myogenic subpopulations and the function of canonical Wnt signaling in regulating these subpopulations. We found that Myf5- and MyoD-expressing myogenic subpopulations exist during embryonic tongue myogenesis. In the Myf5-expressing myogenic progenitors, there is a cell-autonomous requirement for canonical Wnt signaling for cell migration and differentiation. In contrast, the MyoD-expressing subpopulation does not require canonical Wnt signaling during tongue myogenesis. Taken together, our results demonstrate that canonical Wnt signaling differentially regulates the Myf5- and MyoD-expressing subpopulations during tongue myogenesis. © International & American Associations for Dental Research 2015.

  4. FMRI language mapping in children: a panel of language tasks using visual and auditory stimulation without reading or metalinguistic requirements.

    PubMed

    de Guibert, Clément; Maumet, Camille; Ferré, Jean-Christophe; Jannin, Pierre; Biraben, Arnaud; Allaire, Catherine; Barillot, Christian; Le Rumeur, Elisabeth

    2010-06-01

    In the context of presurgical mapping or investigation of neurological and developmental disorders in children, language fMRI raises the issue of the design of a tasks panel achievable by young disordered children. Most language tasks shown to be efficient with healthy children require metalinguistic or reading abilities, therefore adding attentional, cognitive and academic constraints that may be problematic in this context. This study experimented a panel of four language tasks that did not require high attentional skills, reading, or metalinguistic abilities. Two reference tasks involving auditory stimulation (words generation from category, "category"; auditory responsive naming, "definition") were compared with two new tasks involving visual stimulation. These later were designed to tap spontaneous phonological production, in which the names of pictures to be named involve a phonological difference (e.g. in French poule/boule/moule; "phon-diff") or change of segmentation (e.g. in French car/car-te/car-t-on; "phon-seg"). Eighteen healthy children participated (mean age: 12.7+/-3 years). Data processing involved normalizing the data via a matched pairs pediatric template, and inter-task and region of interest analyses with laterality assessment. The reference tasks predominantly activated the left frontal and temporal core language regions, respectively. The new tasks activated these two regions simultaneously, more strongly for the phon-seg task. The union and intersection of all tasks provided more sensitive or specific maps. The study demonstrates that both reference and new tasks highlight core language regions in children, and that the latter are useful for the mapping of spontaneous phonological processing. The use of several different tasks may improve the sensitivity and specificity of fMRI. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Synaptic Plasticity and NO-cGMP-PKG Signaling Coordinately Regulate ERK-Driven Gene Expression in the Lateral Amygdala and in the Auditory Thalamus Following Pavlovian Fear Conditioning

    ERIC Educational Resources Information Center

    Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.

    2010-01-01

    We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the…

  6. Synaptic Plasticity and NO-cGMP-PKG Signaling Coordinately Regulate ERK-Driven Gene Expression in the Lateral Amygdala and in the Auditory Thalamus Following Pavlovian Fear Conditioning

    ERIC Educational Resources Information Center

    Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.

    2010-01-01

    We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the…

  7. Regulatory T cells require TCR signaling for their suppressive function.

    PubMed

    Schmidt, Amanda M; Lu, Wen; Sindhava, Vishal J; Huang, Yanping; Burkhardt, Janis K; Yang, Enjun; Riese, Matthew J; Maltzman, Jonathan S; Jordan, Martha S; Kambayashi, Taku

    2015-05-01

    Regulatory T cells (Tregs) are a subset of CD4(+) T cells that maintain immune tolerance in part by their ability to inhibit the proliferation of conventional CD4(+) T cells (Tconvs). The role of the TCR and the downstream signaling pathways required for this suppressive function of Tregs are not fully understood. To yield insight into how TCR-mediated signals influence Treg suppressive function, we assessed the ability of Tregs with altered TCR-mediated signaling capacity to inhibit Tconv proliferation. Mature Tregs deficient in Src homology 2 domain containing leukocyte protein of 76 kDa (SLP-76), an adaptor protein that nucleates the proximal signaling complex downstream of the TCR, were unable to inhibit Tconv proliferation, suggesting that TCR signaling is required for Treg suppressive function. Moreover, Tregs with defective phospholipase C γ (PLCγ) activation due to a Y145F mutation of SLP-76 were also defective in their suppressive function. Conversely, enhancement of diacylglycerol-mediated signaling downstream of PLCγ by genetic ablation of a negative regulator of diacylglycerol kinase ζ increased the suppressive ability of Tregs. Because SLP-76 is also important for integrin activation and signaling, we tested the role of integrin activation in Treg-mediated suppression. Tregs lacking the adaptor proteins adhesion and degranulation promoting adapter protein or CT10 regulator of kinase/CT10 regulator of kinase-like, which are required for TCR-mediated integrin activation, inhibited Tconv proliferation to a similar extent as wild-type Tregs. Together, these data suggest that TCR-mediated PLCγ activation, but not integrin activation, is required for Tregs to inhibit Tconv proliferation.

  8. Subcortical Modulation in Auditory Processing and Auditory Hallucinations

    PubMed Central

    Ikuta, Toshikazu; DeRosse, Pamela; Argyelan, Miklos; Karlsgodt, Katherine H.; Kingsley, Peter B.; Szeszko, Philip R.; Malhotra, Anil K.

    2015-01-01

    Hearing perception in individuals with auditory hallucinations has not been well studied. Auditory hallucinations have previously been shown to involve primary auditory cortex activation. This activation suggests that auditory hallucinations activate the terminal of the auditory pathway as if auditory signals are submitted from the cochlea, and that a hallucinatory event is therefore perceived as hearing. The primary auditory cortex is stimulated by some unknown source that is outside of the auditory pathway. The current study aimed to assess the outcomes of stimulating the primary auditory cortex through the auditory pathway in individuals who have experienced auditory hallucinations. Sixteen patients with schizophrenia underwent functional magnetic resonance imaging (fMRI) sessions, as well as hallucination assessments. During the fMRI session, auditory stimuli were presented in one-second intervals at times when scanner noise was absent. Participants listened to auditory stimuli of sine waves (SW) (4 kHz-5.5 kHz), English words (EW), and acoustically reversed English words (arEW) in a block design fashion. The arEW were employed to deliver the sound of a human voice with minimal linguistic components. Patients’ auditory hallucination severity was assessed by the auditory hallucination item of the Brief Psychiatric Rating Scale (BPRS). During perception of arEW when compared with perception of SW, bilateral activation of the globus pallidus correlated with severity of auditory hallucinations. EW when compared with arEW did not correlate with auditory hallucination severity. Our findings suggest that the sensitivity of the globus pallidus to the human voice is associated with the severity of auditory hallucination. PMID:26275927

  9. Severe auditory processing disorder secondary to viral meningoencephalitis.

    PubMed

    Pillion, Joseph P; Shiffler, Dorothy E; Hoon, Alexander H; Lin, Doris D M

    2014-06-01

    To describe auditory function in an individual with bilateral damage to the temporal and parietal cortex. Case report. A previously healthy 17-year old male is described who sustained extensive cortical injury following an episode of viral meningoencephalitis. He developed status epilepticus and required intubation and multiple anticonvulsants. Serial brain MRIs showed bilateral temporoparietal signal changes reflecting extensive damage to language areas and the first transverse gyrus of Heschl on both sides. The patient was referred for assessment of auditory processing but was so severely impaired in speech processing that he was unable to complete any formal tests of his speech processing abilities. Audiological assessment utilizing objective measures of auditory function established the presence of normal peripheral auditory function and illustrates the importance of the use of objective measures of auditory function in patients with injuries to the auditory cortex. Use of objective measures of auditory function is essential in establishing the presence of normal peripheral auditory function in individuals with cortical damage who may not be able to cooperate sufficiently for assessment utilizing behavioral measures of auditory function.

  10. Potyviruses differ in their requirement for TOR signalling.

    PubMed

    Ouibrahim, Laurence; Rubio, Ana Giner; Moretti, André; Montané, Marie-Hélène; Menand, Benoît; Meyer, Christian; Robaglia, Christophe; Caranta, Carole

    2015-09-01

    Potyviruses are important plant pathogens that rely on many plant cellular processes for successful infection. TOR (target of rapamycin) signalling is a key eukaryotic energy-signalling pathway controlling many cellular processes such as translation and autophagy. The dependence of potyviruses on active TOR signalling was examined. Arabidopsis lines downregulated for TOR by RNAi were challenged with the potyviruses watermelon mosaic virus (WMV) and turnip mosaic virus (TuMV). WMV accumulation was found to be severely altered while TuMV accumulation was only slightly delayed. In another approach, using AZD-8055, an active site inhibitor of the TOR kinase, WMV infection was found to be strongly affected. Moreover, AZD-8055 application can cure WMV infection. In contrast, TuMV infection was not affected by AZD-8055. This suggests that potyviruses have different cellular requirements for active plant TOR signalling.

  11. 46 CFR 161.013-7 - Signal requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ELECTRICAL EQUIPMENT Electric Distress Light for Boats § 161.013-7 Signal requirements. (a) An electric light must have a flash characteristic of the International Morse Code for...

  12. 46 CFR 161.013-7 - Signal requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ELECTRICAL EQUIPMENT Electric Distress Light for Boats § 161.013-7 Signal requirements. (a) An electric light must have a flash characteristic of the International Morse Code for...

  13. Sensory augmentation: integration of an auditory compass signal into human perception of space

    PubMed Central

    Schumann, Frank; O’Regan, J. Kevin

    2017-01-01

    Bio-mimetic approaches to restoring sensory function show great promise in that they rapidly produce perceptual experience, but have the disadvantage of being invasive. In contrast, sensory substitution approaches are non-invasive, but may lead to cognitive rather than perceptual experience. Here we introduce a new non-invasive approach that leads to fast and truly perceptual experience like bio-mimetic techniques. Instead of building on existing circuits at the neural level as done in bio-mimetics, we piggy-back on sensorimotor contingencies at the stimulus level. We convey head orientation to geomagnetic North, a reliable spatial relation not normally sensed by humans, by mimicking sensorimotor contingencies of distal sounds via head-related transfer functions. We demonstrate rapid and long-lasting integration into the perception of self-rotation. Short training with amplified or reduced rotation gain in the magnetic signal can expand or compress the perceived extent of vestibular self-rotation, even with the magnetic signal absent in the test. We argue that it is the reliability of the magnetic signal that allows vestibular spatial recalibration, and the coding scheme mimicking sensorimotor contingencies of distal sounds that permits fast integration. Hence we propose that contingency-mimetic feedback has great potential for creating sensory augmentation devices that achieve fast and genuinely perceptual experiences. PMID:28195187

  14. Sensory augmentation: integration of an auditory compass signal into human perception of space.

    PubMed

    Schumann, Frank; O'Regan, J Kevin

    2017-02-14

    Bio-mimetic approaches to restoring sensory function show great promise in that they rapidly produce perceptual experience, but have the disadvantage of being invasive. In contrast, sensory substitution approaches are non-invasive, but may lead to cognitive rather than perceptual experience. Here we introduce a new non-invasive approach that leads to fast and truly perceptual experience like bio-mimetic techniques. Instead of building on existing circuits at the neural level as done in bio-mimetics, we piggy-back on sensorimotor contingencies at the stimulus level. We convey head orientation to geomagnetic North, a reliable spatial relation not normally sensed by humans, by mimicking sensorimotor contingencies of distal sounds via head-related transfer functions. We demonstrate rapid and long-lasting integration into the perception of self-rotation. Short training with amplified or reduced rotation gain in the magnetic signal can expand or compress the perceived extent of vestibular self-rotation, even with the magnetic signal absent in the test. We argue that it is the reliability of the magnetic signal that allows vestibular spatial recalibration, and the coding scheme mimicking sensorimotor contingencies of distal sounds that permits fast integration. Hence we propose that contingency-mimetic feedback has great potential for creating sensory augmentation devices that achieve fast and genuinely perceptual experiences.

  15. Mouse Spermatogenesis Requires Classical and Nonclassical Testosterone Signaling.

    PubMed

    Toocheck, Corey; Clister, Terri; Shupe, John; Crum, Chelsea; Ravindranathan, Preethi; Lee, Tae-Kyung; Ahn, Jung-Mo; Raj, Ganesh V; Sukhwani, Meena; Orwig, Kyle E; Walker, William H

    2016-01-01

    Testosterone acts though the androgen receptor in Sertoli cells to support germ cell development (spermatogenesis) and male fertility, but the molecular and cellular mechanisms by which testosterone acts are not well understood. Previously, we found that in addition to acting through androgen receptor to directly regulate gene expression (classical testosterone signaling pathway), testosterone acts through a nonclassical pathway via the androgen receptor to rapidly activate kinases that are known to regulate spermatogenesis. In this study, we provide the first evidence that nonclassical testosterone signaling occurs in vivo as the MAP kinase cascade is rapidly activated in Sertoli cells within the testis by increasing testosterone levels in the rat. We find that either classical or nonclassical signaling regulates testosterone-mediated Rhox5 gene expression in Sertoli cells within testis explants. The selective activation of classical or nonclassical signaling pathways in Sertoli cells within testis explants also resulted in the differential activation of the Zbtb16 and c-Kit genes in adjacent spermatogonia germ cells. Delivery of an inhibitor of either pathway to Sertoli cells of mouse testes disrupted the blood-testis barrier that is essential for spermatogenesis. Furthermore, an inhibitor of nonclassical testosterone signaling blocked meiosis in pubertal mice and caused the loss of meiotic and postmeiotic germ cells in adult mouse testes. An inhibitor of the classical pathway caused the premature release of immature germ cells. Collectively, these observations indicate that classical and nonclassical testosterone signaling regulate overlapping and distinct functions that are required for the maintenance of spermatogenesis and male fertility.

  16. Hwanggunchungyitang prevents cadmium-induced ototoxicity through suppression of the activation of caspase-9 and extracellular signal-related kinase in auditory HEI-OC1 cells.

    PubMed

    Kim, Su-Jin; Shin, Bong-Gi; Choi, In-Young; Kim, Dong-Hyun; Kim, Min-Cheol; Myung, Noh-Yil; Moon, Phil-Dong; Lee, Jeong-Han; An, Hyo-Jin; Kim, Na-Hyung; Lee, Joo-Young; So, Hong-Seob; Park, Rae-Kil; Jeong, Hyun-Ja; Um, Jae-Young; Kim, Hyung-Min; Hong, Seung-Heon

    2009-02-01

    Hwanggunchungyitang (HGCYT) is a newly designed herbal drug formula for the purpose of treating auditory diseases. A number of heavy metals have been associated with toxic effects to the peripheral or central auditory system. Cadmium (Cd(2+)) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. However, the auditory effect of Cd(2+) is not poorly understood. The purpose of the present study was to investigate whether HGCYT prevent the ototoxic effects induced by Cd(2+) in auditory cell line, HEI-OC1. HGCYT inhibited the cell death, reactive oxygen species generation (ROS), activation of caspase-9, and extracellular signal-related kinase (ERK) induced by Cd(2+). In addition, we observed that cochlear hair cells in middle turn were damaged by Cd(2+). However, HGCYT prevented the destruction of hair cell arrays of the rat primary organ of Corti explants in the presence of Cd(2+). These results support the notion that ROS are involved in Cd(2+) ototoxicity and suggest HGCYT therapeutic usefulness, against Cd(2+)-induced activation of caspase-9 and ERK.

  17. Visual influences on auditory spatial learning

    PubMed Central

    King, Andrew J.

    2008-01-01

    The visual and auditory systems frequently work together to facilitate the identification and localization of objects and events in the external world. Experience plays a critical role in establishing and maintaining congruent visual–auditory associations, so that the different sensory cues associated with targets that can be both seen and heard are synthesized appropriately. For stimulus location, visual information is normally more accurate and reliable and provides a reference for calibrating the perception of auditory space. During development, vision plays a key role in aligning neural representations of space in the brain, as revealed by the dramatic changes produced in auditory responses when visual inputs are altered, and is used throughout life to resolve short-term spatial conflicts between these modalities. However, accurate, and even supra-normal, auditory localization abilities can be achieved in the absence of vision, and the capacity of the mature brain to relearn to localize sound in the presence of substantially altered auditory spatial cues does not require visuomotor feedback. Thus, while vision is normally used to coordinate information across the senses, the neural circuits responsible for spatial hearing can be recalibrated in a vision-independent fashion. Nevertheless, early multisensory experience appears to be crucial for the emergence of an ability to match signals from different sensory modalities and therefore for the outcome of audiovisual-based rehabilitation of deaf patients in whom hearing has been restored by cochlear implantation. PMID:18986967

  18. Epidermal Growth Factor Receptor Cell Survival Signaling Requires Phosphatidylcholine Biosynthesis

    PubMed Central

    Crook, Matt; Upadhyay, Awani; Ido, Liyana J.; Hanna-Rose, Wendy

    2016-01-01

    Identification of pro-cell survival signaling pathways has implications for cancer, cardiovascular, and neurodegenerative disease. We show that the Caenorhabditis elegans epidermal growth factor receptor LET-23 (LET-23 EGFR) has a prosurvival function in counteracting excitotoxicity, and we identify novel molecular players required for this prosurvival signaling. uv1 sensory cells in the C. elegans uterus undergo excitotoxic death in response to activation of the OSM-9/OCR-4 TRPV channel by the endogenous agonist nicotinamide. Activation of LET-23 EGFR can effectively prevent this excitotoxic death. We investigate the roles of signaling pathways known to act downstream of LET-23 EGFR in C. elegans and find that the LET-60 Ras/MAPK pathway, but not the IP3 receptor pathway, is required for efficient LET-23 EGFR activity in its prosurvival function. However, activation of LET-60 Ras/MAPK pathway does not appear to be sufficient to fully mimic LET-23 EGFR activity. We screen for genes that are required for EGFR prosurvival function and uncover a role for phosphatidylcholine biosynthetic enzymes in EGFR prosurvival function. Finally, we show that exogenous application of phosphatidylcholine is sufficient to prevent some deaths in this excitotoxicity model. Our work implicates regulation of lipid synthesis downstream of EGFR in cell survival and death decisions. PMID:27605519

  19. Functional MRI of Auditory Responses in the Zebra Finch Forebrain Reveals a Hierarchical Organisation Based on Signal Strength but Not Selectivity

    PubMed Central

    Boumans, Tiny; Gobes, Sharon M. H.; Poirier, Colline; Theunissen, Frederic E.; Vandersmissen, Liesbeth; Pintjens, Wouter; Verhoye, Marleen; Bolhuis, Johan J.; Van der Linden, Annemie

    2008-01-01

    Background Male songbirds learn their songs from an adult tutor when they are young. A network of brain nuclei known as the ‘song system’ is the likely neural substrate for sensorimotor learning and production of song, but the neural networks involved in processing the auditory feedback signals necessary for song learning and maintenance remain unknown. Determining which regions show preferential responsiveness to the bird's own song (BOS) is of great importance because neurons sensitive to self-generated vocalisations could mediate this auditory feedback process. Neurons in the song nuclei and in a secondary auditory area, the caudal medial mesopallium (CMM), show selective responses to the BOS. The aim of the present study is to investigate the emergence of BOS selectivity within the network of primary auditory sub-regions in the avian pallium. Methods and Findings Using blood oxygen level-dependent (BOLD) fMRI, we investigated neural responsiveness to natural and manipulated self-generated vocalisations and compared the selectivity for BOS and conspecific song in different sub-regions of the thalamo-recipient area Field L. Zebra finch males were exposed to conspecific song, BOS and to synthetic variations on BOS that differed in spectro-temporal and/or modulation phase structure. We found significant differences in the strength of BOLD responses between regions L2a, L2b and CMM, but no inter-stimuli differences within regions. In particular, we have shown that the overall signal strength to song and synthetic variations thereof was different within two sub-regions of Field L2: zone L2a was significantly more activated compared to the adjacent sub-region L2b. Conclusions Based on our results we suggest that unlike nuclei in the song system, sub-regions in the primary auditory pallium do not show selectivity for the BOS, but appear to show different levels of activity with exposure to any sound according to their place in the auditory processing stream. PMID

  20. Mouse Spermatogenesis Requires Classical and Nonclassical Testosterone Signaling1

    PubMed Central

    Toocheck, Corey; Clister, Terri; Shupe, John; Crum, Chelsea; Ravindranathan, Preethi; Lee, Tae-Kyung; Ahn, Jung-Mo; Raj, Ganesh V.; Sukhwani, Meena; Orwig, Kyle E.; Walker, William H.

    2015-01-01

    Testosterone acts though the androgen receptor in Sertoli cells to support germ cell development (spermatogenesis) and male fertility, but the molecular and cellular mechanisms by which testosterone acts are not well understood. Previously, we found that in addition to acting through androgen receptor to directly regulate gene expression (classical testosterone signaling pathway), testosterone acts through a nonclassical pathway via the androgen receptor to rapidly activate kinases that are known to regulate spermatogenesis. In this study, we provide the first evidence that nonclassical testosterone signaling occurs in vivo as the MAP kinase cascade is rapidly activated in Sertoli cells within the testis by increasing testosterone levels in the rat. We find that either classical or nonclassical signaling regulates testosterone-mediated Rhox5 gene expression in Sertoli cells within testis explants. The selective activation of classical or nonclassical signaling pathways in Sertoli cells within testis explants also resulted in the differential activation of the Zbtb16 and c-Kit genes in adjacent spermatogonia germ cells. Delivery of an inhibitor of either pathway to Sertoli cells of mouse testes disrupted the blood-testis barrier that is essential for spermatogenesis. Furthermore, an inhibitor of nonclassical testosterone signaling blocked meiosis in pubertal mice and caused the loss of meiotic and postmeiotic germ cells in adult mouse testes. An inhibitor of the classical pathway caused the premature release of immature germ cells. Collectively, these observations indicate that classical and nonclassical testosterone signaling regulate overlapping and distinct functions that are required for the maintenance of spermatogenesis and male fertility. PMID:26607719

  1. Neuroendocrine regulation of Drosophila metamorphosis requires TGFβ/Activin signaling

    PubMed Central

    Gibbens, Ying Y.; Warren, James T.; Gilbert, Lawrence I.; O'Connor, Michael B.

    2011-01-01

    In insects, initiation of metamorphosis requires a surge in the production of the steroid hormone 20-hydroxyecdysone from the prothoracic gland, the primary endocrine organ of juvenile larvae. Here, we show that blocking TGFβ/Activin signaling, specifically in the Drosophila prothoracic gland, results in developmental arrest prior to metamorphosis. The terminal, giant third instar larval phenotype results from a failure to induce the large rise in ecdysteroid titer that triggers metamorphosis. We further demonstrate that activin signaling regulates competence of the prothoracic gland to receive PTTH and insulin signals, and that these two pathways act at the mRNA and post-transcriptional levels, respectively, to control ecdysone biosynthetic enzyme expression. This dual regulatory circuitry may provide a cross-check mechanism to ensure that both developmental and nutritional inputs are synchronized before initiating the final genetic program leading to reproductive adult development. As steroid hormone production in C. elegans and mammals is also influenced by TGFβ/Activin signaling, this family of secreted factors may play a general role in regulating developmental transitions across phyla. PMID:21613324

  2. Distinct roles of TRP channels in auditory transduction and amplification in Drosophila.

    PubMed

    Lehnert, Brendan P; Baker, Allison E; Gaudry, Quentin; Chiang, Ann-Shyn; Wilson, Rachel I

    2013-01-09

    Auditory receptor cells rely on mechanically gated channels to transform sound stimuli into neural activity. Several TRP channels have been implicated in Drosophila auditory transduction, but mechanistic studies have been hampered by the inability to record subthreshold signals from receptor neurons. Here, we develop a non-invasive method for measuring these signals by recording from a central neuron that is electrically coupled to a genetically defined population of auditory receptor cells. We find that the TRPN family member NompC, which is necessary for the active amplification of sound-evoked motion by the auditory organ, is not required for transduction in auditory receptor cells. Instead, NompC sensitizes the transduction complex to movement and precisely regulates the static forces on the complex. In contrast, the TRPV channels Nanchung and Inactive are required for responses to sound, suggesting they are components of the transduction complex. Thus, transduction and active amplification are genetically separable processes in Drosophila hearing.

  3. Required signal-to-interference ratios for shortwave broadcasting

    NASA Astrophysics Data System (ADS)

    Lane, George

    1997-09-01

    The required signal-to-Interference (RSI) ratio for a specified grade of HF radio service is the hourly median wanted signal power at the input of the receiver needed relative to the sum of the hourly median unwanted signal power and the hourly median radio noise power in the RF bandwidth of the receiver, adjusted so that the hourly median ratio will not fall below the RSI ratio more than a certain percentage of the time due to minute-to-minute fading within the hour. Shortwave listeners are well aware of the deleterious effects of cochannel and adjacent channel interference. This type of interference is especially prevalent in the overcrowded international broadcast bands where it is manifested by cross talk and a beat note produced in the receiver by the carrier of the unwanted signal. Yet little agreement exists as to the magnitude of the amplitude-modulated, double sideband (AM-DSB) interfering signal that can be tolerated by the listener. Numerous protection ratios have been proposed in the literature, as well as by elements of the International Telecommunication Union. These values tend to range from 17 dB [International Frequency Registration Board, 1989] to as high as 50 dB for "good commercial quality," offset in carrier frequency of 500 Hz and 10 dB short-term fade protection [CCIR, 1970]. In this paper, several significant experiments are reviewed for the purpose of normalizing their findings to a common set of parameters. The parameters relate to articulation scoring, type of noise (if used), fading of wanted and unwanted signals, type of interference, listener skill, bandwidth of the receiver, carrier frequency offset, etc. From this compilation of normalized data, RSI values are recommended as they relate to the desired broadcast quality and the signal-to-noise ratio of the wanted signal. The RSI ratios are compatible for use in HF sky wave prediction programs that contain appropriate RF noise and interference combining subroutines. The recommended

  4. Responses of neurons in the auditory pathway of the barn owl to partially correlated binaural signals.

    PubMed

    Albeck, Y; Konishi, M

    1995-10-01

    VLVa and ICcC. 5. Almost all ramp neurons occurred in either ICx or ICcLS where neurons are more broadly tuned to frequency than those in the lower nuclei. The synthesis of this response type requires, however, not only the convergence of different frequency channels but also inhibition between different ITD channels. We modeled the ramp response as a three-step process. First, different spectral channels converge to create broad frequency tuning. The response to variation in BC will be linear (or parabolic) because it is a sum of linear (parabolic) responses. Second, the activity in some adjacent ITD channels is subtracted by lateral inhibition. Finally, the result is rectified using a high threshold to avoid negative activity.

  5. Chitosan signaling in guard cells requires endogenous salicylic acid.

    PubMed

    Prodhan, Md Yeasin; Issak, Mohammad; Nakamura, Toshiyuki; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

    2017-08-01

    An elicitor chitosan (CHT) induces stomatal closure but the mechanism remains to be clarified. A phytohormone salicylic acid (SA) is crucial for elicitor-induced defense signaling in plants. Here we investigated whether endogenous SA is required for CHT signaling in guard cells. In the SA-deficient nahG mutant, treatment of CHT did not induce either apoplastic reactive oxygen species (ROS) production or stomatal closure but co-treatment of CHT and SA induced both apoplastic ROS production and stomatal closure, indicating the involvement of endogenous SA in CHT-induced apoplastic ROS production and CHT-induced stomatal closure. Furthermore, CHT induced transient cytosolic free calcium concentration increments in the nahG mutant in the presence of exogenous SA but not in the absence of exogenous SA. These results provide evidence that endogenous SA is a crucial element in CHT-induced stomatal closure.

  6. Pronephric Tubulogenesis Requires Daam1-Mediated Planar Cell Polarity Signaling

    PubMed Central

    Gomez de la Torre Canny, Sol; Jang, Chuan-Wei; Cho, Kyucheol; Ji, Hong; Wagner, Daniel S.; Jones, Elizabeth A.; Habas, Raymond

    2011-01-01

    Canonical β-catenin-mediated Wnt signaling is essential for the induction of nephron development. Noncanonical Wnt/planar cell polarity (PCP) pathways contribute to processes such as cell polarization and cytoskeletal modulation in several tissues. Although PCP components likely establish the plane of polarization in kidney tubulogenesis, whether PCP effectors directly modulate the actin cytoskeleton in tubulogenesis is unknown. Here, we investigated the roles of Wnt PCP components in cytoskeletal assembly during kidney tubule morphogenesis in Xenopus laevis and zebrafish. We found that during tubulogenesis, the developing pronephric anlagen expresses Daam1 and its interacting Rho-GEF (WGEF), which compose one PCP/noncanonical Wnt pathway branch. Knockdown of Daam1 resulted in reduced expression of late pronephric epithelial markers with no apparent effect upon early markers of patterning and determination. Inhibiting various points in the Daam1 signaling pathway significantly reduced pronephric tubulogenesis. These data indicate that pronephric tubulogenesis requires the Daam1/WGEF/Rho PCP pathway. PMID:21804089

  7. Subcortical processing in auditory communication.

    PubMed

    Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha

    2015-10-01

    The voice is a rich source of information, which the human brain has evolved to decode and interpret. Empirical observations have shown that the human auditory system is especially sensitive to the human voice, and that activity within the voice-sensitive regions of the primary and secondary auditory cortex is modulated by the emotional quality of the vocal signal, and may therefore subserve, with frontal regions, the cognitive ability to correctly identify the speaker's affective state. So far, the network involved in the processing of vocal affect has been mainly characterised at the cortical level. However, anatomical and functional evidence suggests that acoustic information relevant to the affective quality of the auditory signal might be processed prior to the auditory cortex. Here we review the animal and human literature on the main subcortical structures along the auditory pathway, and propose a model whereby the distinction between different types of vocal affect in auditory communication begins at very early stages of auditory processing, and relies on the analysis of individual acoustic features of the sound signal. We further suggest that this early feature-based decoding occurs at a subcortical level along the ascending auditory pathway, and provides a preliminary coarse (but fast) characterisation of the affective quality of the auditory signal before the more refined (but slower) cortical processing is completed.

  8. Morphological and physiological development of auditory synapses

    PubMed Central

    Yu, Wei-Ming; Goodrich, Lisa V.

    2014-01-01

    Acoustic communication requires gathering, transforming, and interpreting diverse sound cues. To achieve this, all the spatial and temporal features of complex sound stimuli must be captured in the firing patterns of the primary sensory neurons and then accurately transmitted along auditory pathways for additional processing. The mammalian auditory system relies on several synapses with unique properties in order to meet this task: the auditory ribbon synapses, the endbulb of Held, and the calyx of Held. Each of these synapses develops morphological and electrophysiological characteristics that enable the remarkably precise signal transmission necessary for conveying the miniscule differences in timing that underly sound localization. In this article, we review the current knowledge of how these synapses develop and mature to acquire the specialized features necessary for the sense of hearing. PMID:24508369

  9. Auditory Artifacts due to Switching Head-Related Transfer Functions of a Dynamic Virtual Auditory Display

    NASA Astrophysics Data System (ADS)

    Otani, Makoto; Hirahara, Tatsuya

    Auditory artifacts due to switching head-related transfer functions (HRTFs) are investigated, using a software-implemented dynamic virtual auditory display (DVAD) developed by the authors. The DVAD responds to a listener's head rotation using a head-tracking device and switching HRTFs to present a highly realistic 3D virtual auditory space to the listener. The DVAD operates on Windows XP and does not require high-performance computers. A total system latency (TSL), which is the delay between head motion and the corresponding change of the ear input signal, is a significant factor of DVADs. The measured TSL of our DVAD is about 50ms, which is sufficient for practical applications and localization experiments. Another matter of concern is the auditory artifact in DVADs caused by switching HRTFs. Switching HRTFs gives rise to wave discontinuity of synthesized binaural signals, which can be perceived as click noises that degrade the quality of presented sound image. A subjective test and excitation patterns (EPNs) analysis using an auditory filter are performed with various source signals and HRTF spatial resolutions. The results of the subjective test reveal that click noise perception depends on the source signal and the HRTF spatial resolution. Furthermore, EPN analysis reveals that switching HRTFs significantly distorts the EPNs at the off signal frequencies. Such distortions, however, are masked perceptually by broad-bandwidth source signals, whereas they are not masked by narrow-bandwidth source signals, thereby making the click noise more detectable. A higher HRTF spatial resolution leads to smaller distortions. But, depending on the source signal, perceivable click noises still remain even with 0.5-degree spatial resolution, which is less than minimum audible angle (1 degree in front).

  10. Wnt signaling is required for long-term memory formation

    PubMed Central

    Tan, Ying; Yu, Dinghui; Busto, Germain U.; Wilson, Curtis; Davis, Ronald L.

    2013-01-01

    SUMMARY Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNA interference approach. Interfering with β-catenin expression in the adult mushroom body neurons specifically impaired long-term memory without altering short-term memory. The impairment was reversible, rescued with expression of a wild-type β-catenin transgene, and correlated with a disruption of a cellular long-term memory trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt co-receptor, also impaired long-term memory. Wingless expression in wild type flies was transiently elevated in the brain after long-term memory conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in the adult mushroom bodies impairs long-term memory, collectively indicating that this pathway mechanistically underlies this specific form of memory. PMID:24035392

  11. Requirement for Pangolin/dTCF in Drosophila Wingless signaling.

    PubMed

    Schweizer, Liang; Nellen, Denise; Basler, Konrad

    2003-05-13

    The Wingless (Wg) protein is a secreted glycoprotein involved in intercellular signaling. On activation of the Wg signaling pathway, Armadillo is stabilized, causing target genes to be activated by the transcription factor Pangolin (Pan). This study investigated the roles of Pan in the developing wing of Drosophila by clonal analysis. Three different aspects of wing development were examined: cell proliferation, wing margin specification, and wg self-refinement. Our results indicate that Pan function is critically required for all three of these processes. Consequently, lack of pan causes a severe reduction in the activity of the Wg target genes Distalless and vestigial within their normal domain of expression. Loss of pan function does not, however, lead to a derepression of these genes outside this domain. Thus, although Pan is positively required for the induction of Wg targets in the wing imaginal disk, it does not appear to play a default repressor function in the absence of Wg input. In contrast, lack of zygotic pan function causes a milder phenotype than that caused by the lack of wg function in the embryo. We show that this difference cannot be attributed to maternally provided pan product, indicating that a Pan repressor function usually prevents the expression of embryonic Wg targets. Together, our results suggest that for embryonic patterning the activator as well as repressor forms of Pan play important roles, while for wing development Pan operates primarily in the activator mode.

  12. Requirement for Pangolin/dTCF in Drosophila Wingless signaling

    PubMed Central

    Schweizer, Liang; Nellen, Denise; Basler, Konrad

    2003-01-01

    The Wingless (Wg) protein is a secreted glycoprotein involved in intercellular signaling. On activation of the Wg signaling pathway, Armadillo is stabilized, causing target genes to be activated by the transcription factor Pangolin (Pan). This study investigated the roles of Pan in the developing wing of Drosophila by clonal analysis. Three different aspects of wing development were examined: cell proliferation, wing margin specification, and wg self-refinement. Our results indicate that Pan function is critically required for all three of these processes. Consequently, lack of pan causes a severe reduction in the activity of the Wg target genes Distalless and vestigial within their normal domain of expression. Loss of pan function does not, however, lead to a derepression of these genes outside this domain. Thus, although Pan is positively required for the induction of Wg targets in the wing imaginal disk, it does not appear to play a default repressor function in the absence of Wg input. In contrast, lack of zygotic pan function causes a milder phenotype than that caused by the lack of wg function in the embryo. We show that this difference cannot be attributed to maternally provided pan product, indicating that a Pan repressor function usually prevents the expression of embryonic Wg targets. Together, our results suggest that for embryonic patterning the activator as well as repressor forms of Pan play important roles, while for wing development Pan operates primarily in the activator mode. PMID:12730381

  13. Meaning From Environmental Sounds: Types of Signal-Referent Relations and Their Effect on Recognizing Auditory Icons

    ERIC Educational Resources Information Center

    Keller, Peter; Stevens, Catherine

    2004-01-01

    This article addresses the learnability of auditory icons, that is, environmental sounds that refer either directly or indirectly to meaningful events. Direct relations use the sound made by the target event whereas indirect relations substitute a surrogate for the target. Across 3 experiments, different indirect relations (ecological, in which…

  14. Meaning From Environmental Sounds: Types of Signal-Referent Relations and Their Effect on Recognizing Auditory Icons

    ERIC Educational Resources Information Center

    Keller, Peter; Stevens, Catherine

    2004-01-01

    This article addresses the learnability of auditory icons, that is, environmental sounds that refer either directly or indirectly to meaningful events. Direct relations use the sound made by the target event whereas indirect relations substitute a surrogate for the target. Across 3 experiments, different indirect relations (ecological, in which…

  15. From sensation to percept: the neural signature of auditory event-related potentials.

    PubMed

    Joos, Kathleen; Gilles, Annick; Van de Heyning, Paul; De Ridder, Dirk; Vanneste, Sven

    2014-05-01

    An external auditory stimulus induces an auditory sensation which may lead to a conscious auditory perception. Although the sensory aspect is well known, it is still a question how an auditory stimulus results in an individual's conscious percept. To unravel the uncertainties concerning the neural correlates of a conscious auditory percept, event-related potentials may serve as a useful tool. In the current review we mainly wanted to shed light on the perceptual aspects of auditory processing and therefore we mainly focused on the auditory late-latency responses. Moreover, there is increasing evidence that perception is an active process in which the brain searches for the information it expects to be present, suggesting that auditory perception requires the presence of both bottom-up, i.e. sensory and top-down, i.e. prediction-driven processing. Therefore, the auditory evoked potentials will be interpreted in the context of the Bayesian brain model, in which the brain predicts which information it expects and when this will happen. The internal representation of the auditory environment will be verified by sensation samples of the environment (P50, N100). When this incoming information violates the expectation, it will induce the emission of a prediction error signal (Mismatch Negativity), activating higher-order neural networks and inducing the update of prior internal representations of the environment (P300).

  16. Endodermal Wnt signaling is required for tracheal cartilage formation.

    PubMed

    Snowball, John; Ambalavanan, Manoj; Whitsett, Jeffrey; Sinner, Debora

    2015-09-01

    Tracheobronchomalacia is a common congenital defect in which the walls of the trachea and bronchi lack of adequate cartilage required for support of the airways. Deletion of Wls, a cargo receptor mediating Wnt ligand secretion, in the embryonic endoderm using ShhCre mice inhibited formation of tracheal-bronchial cartilaginous rings. The normal dorsal-ventral patterning of tracheal mesenchyme was lost. Smooth muscle cells, identified by Acta2 staining, were aberrantly located in ventral mesenchyme of the trachea, normally the region of Sox9 expression in cartilage progenitors. Wnt/β-catenin activity, indicated by Axin2 LacZ reporter, was decreased in tracheal mesenchyme of Wls(f/f);Shh(Cre/+) embryos. Proliferation of chondroblasts was decreased and reciprocally, proliferation of smooth muscle cells was increased in Wls(f/f);Shh(Cre/+) tracheal tissue. Expression of Tbx4, Tbx5, Msx1 and Msx2, known to mediate cartilage and muscle patterning, were decreased in tracheal mesenchyme of Wls(f/f);Shh(Cre/+) embryos. Ex vivo studies demonstrated that Wnt7b and Wnt5a, expressed by the epithelium of developing trachea, and active Wnt/β-catenin signaling are required for tracheal chondrogenesis before formation of mesenchymal condensations. In conclusion, Wnt ligands produced by the tracheal epithelium pattern the tracheal mesenchyme via modulation of gene expression and cell proliferation required for proper tracheal cartilage and smooth muscle differentiation.

  17. Endodermal Wnt signaling is required for tracheal cartilage formation

    PubMed Central

    Snowball, John; Ambalavanan, Manoj; Whitsett, Jeffrey; Sinner, Debora

    2015-01-01

    Tracheobronchomalacia is a common congenital defect in which the walls of the trachea and bronchi lack of adequate cartilage required for support of the airways. Deletion of Wls, a cargo receptor mediating Wnt ligand secretion, in the embryonic endoderm using ShhCre mice inhibited formation of tracheal-bronchial cartilaginous rings. The normal dorsal-ventral patterning of tracheal mesenchyme was lost. Smooth muscle cells, identified by Acta2 staining, were aberrantly located in ventral mesenchyme of the trachea, normally the region of Sox9 expression in cartilage progenitors. Wnt/β-catenin activity, indicated by Axin2 LacZ reporter, was decreased in tracheal mesenchyme of Wlsf/f;ShhCre/+ embryos. Proliferation of chondroblasts was decreased and reciprocally, proliferation of smooth muscle cells was increased in Wlsf/f;ShhCre/+ tracheal tissue. Expression of Tbx4, Tbx5, Msx1 and Msx2, known to mediate cartilage and muscle patterning, were decreased in tracheal mesenchyme of Wlsf/f;ShhCre/+ embryos. Ex vivo studies demonstrated that Wnt7b and Wnt5a, expressed by the epithelium of developing trachea, and active Wnt/β-catenin signaling are required for tracheal chondrogenesis before formation of mesenchymal condensations. In conclusion, Wnt ligands produced by the tracheal epithelium pattern the tracheal mesenchyme via modulation of gene expression and cell proliferation required for proper tracheal cartilage and smooth muscle differentiation. PMID:26093309

  18. Myocardium and BMP signaling are required for endocardial differentiation.

    PubMed

    Palencia-Desai, Sharina; Rost, Megan S; Schumacher, Jennifer A; Ton, Quynh V; Craig, Michael P; Baltrunaite, Kristina; Koenig, Andrew L; Wang, Jinhu; Poss, Kenneth D; Chi, Neil C; Stainier, Didier Y R; Sumanas, Saulius

    2015-07-01

    Endocardial and myocardial progenitors originate in distinct regions of the anterior lateral plate mesoderm and migrate to the midline where they coalesce to form the cardiac tube. Endocardial progenitors acquire a molecular identity distinct from other vascular endothelial cells and initiate expression of specific genes such as nfatc1. Yet the molecular pathways and tissue interactions involved in establishing endocardial identity are poorly understood. The endocardium develops in tight association with cardiomyocytes. To test for a potential role of the myocardium in endocardial morphogenesis, we used two different zebrafish models deficient in cardiomyocytes: the hand2 mutant and a myocardial-specific genetic ablation method. We show that in hand2 mutants endocardial progenitors migrate to the midline but fail to assemble into a cardiac cone and do not express markers of differentiated endocardium. Endocardial differentiation defects were rescued by myocardial but not endocardial-specific expression of hand2. In metronidazole-treated myl7:nitroreductase embryos, myocardial cells were targeted for apoptosis, which resulted in the loss of endocardial nfatc1 expression. However, endocardial cells were present and retained expression of general vascular endothelial markers. We further identified bone morphogenetic protein (BMP) as a candidate myocardium-derived signal required for endocardial differentiation. Chemical and genetic inhibition of BMP signaling at the tailbud stage resulted in severe inhibition of endocardial differentiation while there was little effect on myocardial development. Heat-shock-induced bmp2b expression rescued endocardial nfatc1 expression in hand2 mutants and in myocardium-depleted embryos. Our results indicate that the myocardium is crucial for endocardial morphogenesis and differentiation, and identify BMP as a signal involved in endocardial differentiation.

  19. Auditory agnosia.

    PubMed

    Slevc, L Robert; Shell, Alison R

    2015-01-01

    Auditory agnosia refers to impairments in sound perception and identification despite intact hearing, cognitive functioning, and language abilities (reading, writing, and speaking). Auditory agnosia can be general, affecting all types of sound perception, or can be (relatively) specific to a particular domain. Verbal auditory agnosia (also known as (pure) word deafness) refers to deficits specific to speech processing, environmental sound agnosia refers to difficulties confined to non-speech environmental sounds, and amusia refers to deficits confined to music. These deficits can be apperceptive, affecting basic perceptual processes, or associative, affecting the relation of a perceived auditory object to its meaning. This chapter discusses what is known about the behavioral symptoms and lesion correlates of these different types of auditory agnosia (focusing especially on verbal auditory agnosia), evidence for the role of a rapid temporal processing deficit in some aspects of auditory agnosia, and the few attempts to treat the perceptual deficits associated with auditory agnosia. A clear picture of auditory agnosia has been slow to emerge, hampered by the considerable heterogeneity in behavioral deficits, associated brain damage, and variable assessments across cases. Despite this lack of clarity, these striking deficits in complex sound processing continue to inform our understanding of auditory perception and cognition.

  20. Corneal Wound Healing Requires IKB kinase β Signaling in Keratocytes

    PubMed Central

    Chen, Liang; Mongan, Maureen; Meng, Qinghang; Wang, Qin; Kao, Winston; Xia, Ying

    2016-01-01

    IkB kinase β (IKKβ) is a key signaling kinase for inflammatory responses, but it also plays diverse cell type-specific roles that are not yet fully understood. Here we investigated the role of IKKβ in the cornea using IkkβΔCS mice in which the Ikkβ gene was specifically deleted in the corneal stromal keratocytes. The IkkβΔCS corneas had normal morphology, transparency and thickness; however, they did not heal well from mild alkali burn injury. In contrast to the IkkβF/F corneas that restored transparency in 2 weeks after injury, over 50% of the IkkβΔCS corneas failed to fully recover. They instead developed recurrent haze with increased stromal thickness, severe inflammation and apoptosis. This pathogenesis correlated with sustained myofibroblast transformation with increased α smooth muscle actin (α-SMA) expression, higher levels of senescence β-Gal activity and scar tissue formation at the late stage of wound healing. In addition, the IkkβΔCS corneas displayed elevated expression of hemo-oxygenase-1 (HO-1), a marker of oxidative stress, and activation of stress signaling pathways with increased JNK, c-Jun and SMAD2/3 phosphorylation. These data suggest that IKKβ in keratocytes is required to repress oxidative stress and attenuate fibrogenesis and senescence in corneal wound healing. PMID:26987064

  1. Incorporating Auditory Models in Speech/Audio Applications

    NASA Astrophysics Data System (ADS)

    Krishnamoorthi, Harish

    2011-12-01

    Following the success in incorporating perceptual models in audio coding algorithms, their application in other speech/audio processing systems is expanding. In general, all perceptual speech/audio processing algorithms involve minimization of an objective function that directly/indirectly incorporates properties of human perception. This dissertation primarily investigates the problems associated with directly embedding an auditory model in the objective function formulation and proposes possible solutions to overcome high complexity issues for use in real-time speech/audio algorithms. Specific problems addressed in this dissertation include: 1) the development of approximate but computationally efficient auditory model implementations that are consistent with the principles of psychoacoustics, 2) the development of a mapping scheme that allows synthesizing a time/frequency domain representation from its equivalent auditory model output. The first problem is aimed at addressing the high computational complexity involved in solving perceptual objective functions that require repeated application of auditory model for evaluation of different candidate solutions. In this dissertation, a frequency pruning and a detector pruning algorithm is developed that efficiently implements the various auditory model stages. The performance of the pruned model is compared to that of the original auditory model for different types of test signals in the SQAM database. Experimental results indicate only a 4-7% relative error in loudness while attaining up to 80-90 % reduction in computational complexity. Similarly, a hybrid algorithm is developed specifically for use with sinusoidal signals and employs the proposed auditory pattern combining technique together with a look-up table to store representative auditory patterns. The second problem obtains an estimate of the auditory representation that minimizes a perceptual objective function and transforms the auditory pattern back to

  2. Hey1 and Hey2 control the spatial and temporal pattern of mammalian auditory hair cell differentiation downstream of Hedgehog signaling.

    PubMed

    Benito-Gonzalez, Ana; Doetzlhofer, Angelika

    2014-09-17

    Mechano-sensory hair cells (HCs), housed in the inner ear cochlea, are critical for the perception of sound. In the mammalian cochlea, differentiation of HCs occurs in a striking basal-to-apical and medial-to-lateral gradient, which is thought to ensure correct patterning and proper function of the auditory sensory epithelium. Recent studies have revealed that Hedgehog signaling opposes HC differentiation and is critical for the establishment of the graded pattern of auditory HC differentiation. However, how Hedgehog signaling interferes with HC differentiation is unknown. Here, we provide evidence that in the murine cochlea, Hey1 and Hey2 control the spatiotemporal pattern of HC differentiation downstream of Hedgehog signaling. It has been recently shown that HEY1 and HEY2, two highly redundant HES-related transcriptional repressors, are highly expressed in supporting cell (SC) and HC progenitors (prosensory cells), but their prosensory function remained untested. Using a conditional double knock-out strategy, we demonstrate that prosensory cells form and proliferate properly in the absence of Hey1 and Hey2 but differentiate prematurely because of precocious upregulation of the pro-HC factor Atoh1. Moreover, we demonstrate that prosensory-specific expression of Hey1 and Hey2 and its subsequent graded downregulation is controlled by Hedgehog signaling in a largely FGFR-dependent manner. In summary, our study reveals a critical role for Hey1 and Hey2 in prosensory cell maintenance and identifies Hedgehog signaling as a novel upstream regulator of their prosensory function in the mammalian cochlea. The regulatory mechanism described here might be a broadly applied mechanism for controlling progenitor behavior in the central and peripheral nervous system. Copyright © 2014 the authors 0270-6474/14/3412865-12$15.00/0.

  3. Evaluating auditory perception and communication demands required to carry out work tasks and complimentary hearing resources and skills for older workers with hearing loss.

    PubMed

    Jennings, M B; Shaw, L; Hodgins, H; Kuchar, D A; Bataghva, L Poost-Foroosh

    2010-01-01

    For older workers with acquired hearing loss, this loss as well as the changing nature of work and the workforce, may lead to difficulties and disadvantages in obtaining and maintaining employment. Currently there are very few instruments that can assist workplaces, employers and workers to prepare for older workers with hearing loss or with the evaluation of auditory perception demands of work, especially those relevant to communication, and safety sensitive workplaces that require high levels of communication. This paper introduces key theoretical considerations that informed the development of a new framework, The Audiologic Ergonomic (AE) Framework to guide audiologists, work rehabilitation professionals and workers in developing tools to support the identification and evaluation of auditory perception demands in the workplace, the challenges to communication and the subsequent productivity and safety in the performance of work duties by older workers with hearing loss. The theoretical concepts underpinning this framework are discussed along with next steps in developing tools such as the Canadian Hearing Demands Tool (C-HearD Tool) in advancing approaches to evaluate auditory perception and communication demands in the workplace.

  4. EphB2 signaling regulates lesion-induced axon sprouting but not critical period length in the postnatal auditory brainstem

    PubMed Central

    2013-01-01

    Background Studies of developmental plasticity may provide insight into plasticity during adulthood, when neural circuitry is less responsive to losses or changes in input. In the mammalian auditory brainstem, globular bushy cell axons of the ventral cochlear nucleus (VCN) innervate the contralateral medial nucleus of the trapezoid body (MNTB) principal neurons. VCN axonal terminations in MNTB, known as calyces of Held, are very large and specialized for high-fidelity transmission of auditory information. Following unilateral deafferentation during postnatal development, VCN axons from the intact side form connections with novel targets, including the ipsilateral MNTB. EphB signaling has been shown to play a role in this process during the first postnatal week, but mechanisms involved in this reorganization during later developmental periods remain unknown. Results We found that EphB2 signaling reduces the number of induced ipsilateral projections to the MNTB after unilateral VCN removal at postnatal day seven (P7), but not after removal of the VCN on one side at P10, after the closure of the critical period for lesion-induced innervation of the ipsilateral MNTB. Conclusions Results from this study indicate that molecular mechanisms involved in the development of circuitry may also play a part in rewiring after deafferentation during development, but do not appear to regulate the length of critical periods for plasticity. PMID:23379484

  5. Development of the auditory system.

    PubMed

    Litovsky, Ruth

    2015-01-01

    Auditory development involves changes in the peripheral and central nervous system along the auditory pathways, and these occur naturally, and in response to stimulation. Human development occurs along a trajectory that can last decades, and is studied using behavioral psychophysics, as well as physiologic measurements with neural imaging. The auditory system constructs a perceptual space that takes information from objects and groups, segregates sounds, and provides meaning and access to communication tools such as language. Auditory signals are processed in a series of analysis stages, from peripheral to central. Coding of information has been studied for features of sound, including frequency, intensity, loudness, and location, in quiet and in the presence of maskers. In the latter case, the ability of the auditory system to perform an analysis of the scene becomes highly relevant. While some basic abilities are well developed at birth, there is a clear prolonged maturation of auditory development well into the teenage years. Maturation involves auditory pathways. However, non-auditory changes (attention, memory, cognition) play an important role in auditory development. The ability of the auditory system to adapt in response to novel stimuli is a key feature of development throughout the nervous system, known as neural plasticity.

  6. Development of the auditory system

    PubMed Central

    Litovsky, Ruth

    2015-01-01

    Auditory development involves changes in the peripheral and central nervous system along the auditory pathways, and these occur naturally, and in response to stimulation. Human development occurs along a trajectory that can last decades, and is studied using behavioral psychophysics, as well as physiologic measurements with neural imaging. The auditory system constructs a perceptual space that takes information from objects and groups, segregates sounds, and provides meaning and access to communication tools such as language. Auditory signals are processed in a series of analysis stages, from peripheral to central. Coding of information has been studied for features of sound, including frequency, intensity, loudness, and location, in quiet and in the presence of maskers. In the latter case, the ability of the auditory system to perform an analysis of the scene becomes highly relevant. While some basic abilities are well developed at birth, there is a clear prolonged maturation of auditory development well into the teenage years. Maturation involves auditory pathways. However, non-auditory changes (attention, memory, cognition) play an important role in auditory development. The ability of the auditory system to adapt in response to novel stimuli is a key feature of development throughout the nervous system, known as neural plasticity. PMID:25726262

  7. Supporting cell division is not required for regeneration of auditory hair cells after ototoxic injury in vitro.

    PubMed

    Shang, Jialin; Cafaro, Jon; Nehmer, Rachel; Stone, Jennifer

    2010-06-01

    In chickens, nonsensory supporting cells divide and regenerate auditory hair cells after injury. Anatomical evidence suggests that supporting cells can also transdifferentiate into hair cells without dividing. In this study, we characterized an organ culture model to study auditory hair cell regeneration, and we used these cultures to test if direct transdifferentiation alone can lead to significant hair cell regeneration. Control cultures (organs from posthatch chickens maintained without streptomycin) showed complete hair cell loss in the proximal (high-frequency) region by 5 days. In contrast, a 2-day treatment with streptomycin induced loss of hair cells from all regions by 3 days. Hair cell regeneration proceeded in culture, with the time course of supporting cell division and hair cell differentiation generally resembling in vivo patterns. The degree of supporting cell division depended upon the presence of streptomycin, the epithelial region, the type of culture media, and serum concentration. On average, 87% of the regenerated hair cells lacked the cell division marker BrdU despite its continuous presence, suggesting that most hair cells were regenerated via direct transdifferentiation. Addition of the DNA polymerase inhibitor aphidicolin to culture media prevented supporting cell division, but numerous hair cells were regenerated nonetheless. These hair cells showed signs of functional maturation, including stereociliary bundles and rapid uptake of FM1-43. These observations demonstrate that direct transdifferentiation is a significant mechanism of hair cell regeneration in the chicken auditory after streptomycin damage in vitro.

  8. High resolution auditory perception system

    NASA Astrophysics Data System (ADS)

    Alam, Iftekhar; Ghatol, Ashok

    2005-04-01

    Blindness is a sensory disability which is difficult to treat but can to some extent be helped by artificial aids. The paper describes the design aspects of a high resolution auditory perception system, which is designed on the principle of air sonar with binaural perception. This system is a vision substitution aid for enabling blind persons. The blind person wears ultrasonic eyeglasses which has ultrasonic sensor array embedded on it. The system has been designed to operate in multiresolution modes. The ultrasonic sound from the transmitter array is reflected back by the objects, falling in the beam of the array and is received. The received signal is converted to a sound signal, which is presented stereophonically for auditory perception. A detailed study has been done as the background work required for the system implementation; the appropriate range analysis procedure, analysis of space-time signals, the acoustic sensors study, amplification methods and study of the removal of noise using filters. Finally the system implementation including both the hardware and the software part of it has been described. Experimental results on actual blind subjects and inferences obtained during the study have also been included.

  9. Only signaling modules that discriminate sharply between stimulatory and nonstimulatory inputs require basal signaling for fast cellular responses

    NASA Astrophysics Data System (ADS)

    Artomov, Mykyta; Kardar, Mehran; Chakraborty, Arup K.

    2010-09-01

    In many types of cells, binding of molecules to their receptors enables cascades of intracellular chemical reactions to take place (signaling). However, a low level of signaling also occurs in most unstimulated cells. Such basal signaling in resting cells can have many functions, one of which is that it is thought to be required for fast cellular responses to external stimuli. A mechanistic understanding of why this is true and which features of cellular signaling networks make basal signaling necessary for fast responses is unknown. We address this issue by obtaining the time required for activation of common types of cell signaling modules with and without basal signaling. Our results show that the absence of basal signaling does not have any dramatic effects on the response time for signaling modules that exhibit a graded response to increasing stimulus levels. In sharp contrast, signaling modules that exhibit sharp dose-response curves which discriminate sensitively between stimuli to which the cell needs to respond and low-grade inputs (or stochastic noise) require basal signaling for fast cellular responses. In such cases, we find that an optimal level of basal signaling balances the requirements for fast cellular responses while minimizing spurious activation without appropriate stimulation.

  10. 49 CFR 236.568 - Difference between speeds authorized by roadway signal and cab signal; action required.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Difference between speeds authorized by roadway... Systems Rules and Instructions; Locomotives § 236.568 Difference between speeds authorized by roadway signal and cab signal; action required. If for any reason a cab signal authorizes a speed different from...

  11. 49 CFR 236.568 - Difference between speeds authorized by roadway signal and cab signal; action required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Difference between speeds authorized by roadway... Systems Rules and Instructions; Locomotives § 236.568 Difference between speeds authorized by roadway signal and cab signal; action required. If for any reason a cab signal authorizes a speed different from...

  12. 49 CFR 236.568 - Difference between speeds authorized by roadway signal and cab signal; action required.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Difference between speeds authorized by roadway... Systems Rules and Instructions; Locomotives § 236.568 Difference between speeds authorized by roadway signal and cab signal; action required. If for any reason a cab signal authorizes a speed different from...

  13. 49 CFR 236.568 - Difference between speeds authorized by roadway signal and cab signal; action required.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Difference between speeds authorized by roadway... Systems Rules and Instructions; Locomotives § 236.568 Difference between speeds authorized by roadway signal and cab signal; action required. If for any reason a cab signal authorizes a speed different from...

  14. 49 CFR 236.568 - Difference between speeds authorized by roadway signal and cab signal; action required.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Difference between speeds authorized by roadway... Systems Rules and Instructions; Locomotives § 236.568 Difference between speeds authorized by roadway signal and cab signal; action required. If for any reason a cab signal authorizes a speed different from...

  15. Auditory Imagination.

    ERIC Educational Resources Information Center

    Croft, Martyn

    Auditory imagination is used in this paper to describe a number of issues and activities related to sound and having to do with listening, thinking, recalling, imagining, reshaping, creating, and uttering sounds and words. Examples of auditory imagination in religious and literary works are cited that indicate a belief in an imagined, expected, or…

  16. Fronto-parietal and fronto-temporal theta phase synchronization for visual and auditory-verbal working memory.

    PubMed

    Kawasaki, Masahiro; Kitajo, Keiichi; Yamaguchi, Yoko

    2014-01-01

    In humans, theta phase (4-8 Hz) synchronization observed on electroencephalography (EEG) plays an important role in the manipulation of mental representations during working memory (WM) tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from subjects who were performing auditory-verbal and visual WM tasks; we compared the theta synchronizations when subjects performed either auditory-verbal or visual manipulations in separate WM tasks, or performed both two manipulations in the same WM task. The auditory-verbal WM task required subjects to calculate numbers presented by an auditory-verbal stimulus, whereas the visual WM task required subjects to move a spatial location in a mental representation in response to a visual stimulus. The dual WM task required subjects to manipulate auditory-verbal, visual, or both auditory-verbal and visual representations while maintaining auditory-verbal and visual representations. Our time-frequency EEG analyses revealed significant fronto-temporal theta phase synchronization during auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual WM tasks, but not during visual manipulation tasks. Similarly, we observed significant fronto-parietal theta phase synchronization during visual manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover, we observed significant synchronization in both the fronto-temporal and fronto-parietal theta signals during simultaneous auditory-verbal/visual manipulations. These findings suggest that theta synchronization seems to flexibly connect the brain areas that manipulate WM.

  17. Fronto-parietal and fronto-temporal theta phase synchronization for visual and auditory-verbal working memory

    PubMed Central

    Kawasaki, Masahiro; Kitajo, Keiichi; Yamaguchi, Yoko

    2014-01-01

    In humans, theta phase (4–8 Hz) synchronization observed on electroencephalography (EEG) plays an important role in the manipulation of mental representations during working memory (WM) tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from subjects who were performing auditory-verbal and visual WM tasks; we compared the theta synchronizations when subjects performed either auditory-verbal or visual manipulations in separate WM tasks, or performed both two manipulations in the same WM task. The auditory-verbal WM task required subjects to calculate numbers presented by an auditory-verbal stimulus, whereas the visual WM task required subjects to move a spatial location in a mental representation in response to a visual stimulus. The dual WM task required subjects to manipulate auditory-verbal, visual, or both auditory-verbal and visual representations while maintaining auditory-verbal and visual representations. Our time-frequency EEG analyses revealed significant fronto-temporal theta phase synchronization during auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual WM tasks, but not during visual manipulation tasks. Similarly, we observed significant fronto-parietal theta phase synchronization during visual manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover, we observed significant synchronization in both the fronto-temporal and fronto-parietal theta signals during simultaneous auditory-verbal/visual manipulations. These findings suggest that theta synchronization seems to flexibly connect the brain areas that manipulate WM. PMID:24672496

  18. Neural Correlates of Auditory Processing, Learning and Memory Formation in Songbirds

    NASA Astrophysics Data System (ADS)

    Pinaud, R.; Terleph, T. A.; Wynne, R. D.; Tremere, L. A.

    Songbirds have emerged as powerful experimental models for the study of auditory processing of complex natural communication signals. Intact hearing is necessary for several behaviors in developing and adult animals including vocal learning, territorial defense, mate selection and individual recognition. These behaviors are thought to require the processing, discrimination and memorization of songs. Although much is known about the brain circuits that participate in sensorimotor (auditory-vocal) integration, especially the ``song-control" system, less is known about the anatomical and functional organization of central auditory pathways. Here we discuss findings associated with a telencephalic auditory area known as the caudomedial nidopallium (NCM). NCM has attracted significant interest as it exhibits functional properties that may support higher order auditory functions such as stimulus discrimination and the formation of auditory memories. NCM neurons are vigorously dr iven by auditory stimuli. Interestingly, these responses are selective to conspecific, relative to heterospecific songs and artificial stimuli. In addition, forms of experience-dependent plasticity occur in NCM and are song-specific. Finally, recent experiments employing high-throughput quantitative proteomics suggest that complex protein regulatory pathways are engaged in NCM as a result of auditory experience. These molecular cascades are likely central to experience-associated plasticity of NCM circuitry and may be part of a network of calcium-driven molecular events that support the formation of auditory memory traces.

  19. Cortical cholinergic input is required for normal auditory perception and experience-dependent plasticity in adult ferrets.

    PubMed

    Leach, Nicholas D; Nodal, Fernando R; Cordery, Patricia M; King, Andrew J; Bajo, Victoria M

    2013-04-10

    The nucleus basalis (NB) in the basal forebrain provides most of the cholinergic input to the neocortex and has been implicated in a variety of cognitive functions related to the processing of sensory stimuli. However, the role that cortical acetylcholine release plays in perception remains unclear. Here we show that selective loss of cholinergic NB neurons that project to the cortex reduces the accuracy with which ferrets localize brief sounds and prevents them from adaptively reweighting auditory localization cues in response to chronic occlusion of one ear. Cholinergic input to the cortex was disrupted by making bilateral injections of the immunotoxin ME20.4-SAP into the NB. This produced a substantial loss of both p75 neurotrophin receptor (p75(NTR))-positive and choline acetyltransferase-positive cells in this region and of acetylcholinesterase-positive fibers throughout the auditory cortex. These animals were significantly impaired in their ability to localize short broadband sounds (40-500 ms in duration) in the horizontal plane, with larger cholinergic cell lesions producing greater performance impairments. Although they localized longer sounds with normal accuracy, their response times were significantly longer than controls. Ferrets with cholinergic forebrain lesions were also less able to relearn to localize sound after plugging one ear. In contrast to controls, they exhibited little recovery of localization performance after behavioral training. Together, these results show that cortical cholinergic inputs contribute to the perception of sound source location under normal hearing conditions and play a critical role in allowing the auditory system to adapt to changes in the spatial cues available.

  20. Involuntary monitoring of sound signals in noise is reflected in the human auditory evoked N1m response.

    PubMed

    Lagemann, Lothar; Okamoto, Hidehiko; Teismann, Henning; Pantev, Christo

    2012-01-01

    Constant sound sequencing as operationalized by repeated stimulation with tones of the same frequency has multiple effects. On the one hand, it activates mechanisms of habituation and refractoriness, which are reflected in the decrease of response amplitude of evoked responses. On the other hand, the constant sequencing acts as spectral cueing, resulting in tones being detected faster and more accurately. With the present study, by means of magnetoencephalography, we investigated the impact of repeated tone stimulation on the N1m auditory evoked fields, while listeners were distracted from the test sounds. We stimulated subjects with trains of either four tones of the same frequency, or with trains of randomly assigned frequencies. The trains were presented either in a silent or in a noisy background. In silence, the patterns of source strength decline originating from repeated stimulation suggested both, refractoriness as well as habituation as underlying mechanisms. In noise, in contrast, there was no indication of source strength decline. Furthermore, we found facilitating effects of constant sequencing regarding the detection of the single tones as indexed by a shortening of N1m latency. We interpret our findings as a correlate of a bottom-up mechanism that is constantly monitoring the incoming auditory information, even when voluntary attention is directed to a different modality.

  1. RNA Type III Secretion Signals that require Hfq

    SciTech Connect

    Niemann, George; Brown, Roslyn N.; Mushamiri, Ivy T.; Nguyen, Nhu T.; Taiwo, Rukayat; Stufkens, Afke; Smith, Richard D.; Adkins, Joshua N.; McDermott, Jason E.; Heffron, Fred

    2013-05-01

    effector proteins from the bacterium to a host cell; however, the secretion signal is poorly defined. Effector N-termini are thought to contain the signal, but they lack homology, possess no identifiable motif, and adopt intrinsically disordered structures. We identified a panel of RNA secretion signals that facilitated reporter translocation into host cells via a mechanism dependent upon the RNA chaperone Hfq. Each of these signals was localized to an RNA leader sequence preceding the translational start codon. To obtain this panel of RNA signals, we fused untranslated leader sequences from 42 different Salmonella effector proteins to the adenylate cyclase reporter (CyaA'), and tested each of them for translocation into J774 macrophages. RNA sequences derived from five effectors, gtgA, cigR, gogB, sseL, and steD were sufficient for CyaA' injection into host cells. The gtgA RNA also directed translocation of the β-lactamase reporter. To determine the mechanism of signal recognition, we identified proteins that bound specifically to the gtgA RNA. One of the unique proteins identified was Hfq. Translocation of all five UTR fusions was abolished in the Hfq mutant, confirming the importance of Hfq. Our results suggest that Hfq may direct a subset of RNA transcripts to the T3S apparatus for translation and secretion. Signal diversity may explain why the T3S signal has been difficult to define.

  2. 14 CFR 171.311 - Signal format requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... signal must be such that during the transmission time, the mean power density above a height of 600...) NAVIGATIONAL FACILITIES NON-FEDERAL NAVIGATION FACILITIES Microwave Landing System (MLS) § 171.311 Signal... period shall not be used. EC15SE91.005 (2) CW. The CW pulse transmissions and the CW angle transmissions...

  3. 14 CFR 171.311 - Signal format requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... signal must be such that during the transmission time, the mean power density above a height of 600...) NAVIGATIONAL FACILITIES NON-FEDERAL NAVIGATION FACILITIES Microwave Landing System (MLS) § 171.311 Signal... period shall not be used. EC15SE91.005 (2) CW. The CW pulse transmissions and the CW angle transmissions...

  4. 14 CFR 171.311 - Signal format requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... signal must be such that during the transmission time, the mean power density above a height of 600...) NAVIGATIONAL FACILITIES NON-FEDERAL NAVIGATION FACILITIES Microwave Landing System (MLS) § 171.311 Signal... period shall not be used. EC15SE91.005 (2) CW. The CW pulse transmissions and the CW angle transmissions...

  5. Evidence of functional connectivity between auditory cortical areas revealed by amplitude modulation sound processing.

    PubMed

    Guéguin, Marie; Le Bouquin-Jeannès, Régine; Faucon, Gérard; Chauvel, Patrick; Liégeois-Chauvel, Catherine

    2007-02-01

    The human auditory cortex includes several interconnected areas. A better understanding of the mechanisms involved in auditory cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. In human, it is difficult to track in vivo neuronal connectivity. We investigated the interarea connection in vivo in the auditory cortex using a method of directed coherence (DCOH) applied to depth auditory evoked potentials (AEPs). This paper presents simultaneous AEPs recordings from insular gyrus (IG), primary and secondary cortices (Heschl's gyrus and planum temporale), and associative areas (Brodmann area [BA] 22) with multilead intracerebral electrodes in response to sinusoidal modulated white noises in 4 epileptic patients who underwent invasive monitoring with depth electrodes for epilepsy surgery. DCOH allowed estimation of the causality between 2 signals recorded from different cortical sites. The results showed 1) a predominant auditory stream within the primary auditory cortex from the most medial region to the most lateral one whatever the modulation frequency, 2) unidirectional functional connection from the primary to secondary auditory cortex, 3) a major auditory propagation from the posterior areas to the anterior ones, particularly at 8, 16, and 32 Hz, and 4) a particular role of Heschl's sulcus dispatching information to the different auditory areas. These findings suggest that cortical processing of auditory information is performed in serial and parallel streams. Our data showed that the auditory propagation could not be associated to a unidirectional traveling wave but to a constant interaction between these areas that could reflect the large adaptive and plastic capacities of auditory cortex. The role of the IG is discussed.

  6. Central auditory disorders: toward a neuropsychology of auditory objects

    PubMed Central

    Goll, Johanna C.; Crutch, Sebastian J.; Warren, Jason D.

    2012-01-01

    Purpose of review Analysis of the auditory environment, source identification and vocal communication all require efficient brain mechanisms for disambiguating, representing and understanding complex natural sounds as ‘auditory objects’. Failure of these mechanisms leads to a diverse spectrum of clinical deficits. Here we review current evidence concerning the phenomenology, mechanisms and brain substrates of auditory agnosias and related disorders of auditory object processing. Recent findings Analysis of lesions causing auditory object deficits has revealed certain broad anatomical correlations: deficient parsing of the auditory scene is associated with lesions involving the parieto-temporal junction, while selective disorders of sound recognition occur with more anterior temporal lobe or extra-temporal damage. Distributed neural networks have been increasingly implicated in the pathogenesis of such disorders as developmental dyslexia, congenital amusia and tinnitus. Auditory category deficits may arise from defective interaction of spectrotemporal encoding and executive and mnestic processes. Dedicated brain mechanisms are likely to process specialised sound objects such as voices and melodies. Summary Emerging empirical evidence suggests a clinically relevant, hierarchical and fractionated neuropsychological model of auditory object processing that provides a framework for understanding auditory agnosias and makes specific predictions to direct future work. PMID:20975559

  7. 33 CFR 150.720 - What are the requirements for sound signals?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false What are the requirements for sound signals? 150.720 Section 150.720 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... are the requirements for sound signals? The sound signal on each pumping platform complex must...

  8. 33 CFR 150.720 - What are the requirements for sound signals?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false What are the requirements for sound signals? 150.720 Section 150.720 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... are the requirements for sound signals? The sound signal on each pumping platform complex must...

  9. 33 CFR 150.720 - What are the requirements for sound signals?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false What are the requirements for sound signals? 150.720 Section 150.720 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... are the requirements for sound signals? The sound signal on each pumping platform complex must...

  10. 33 CFR 150.720 - What are the requirements for sound signals?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false What are the requirements for sound signals? 150.720 Section 150.720 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... are the requirements for sound signals? The sound signal on each pumping platform complex must...

  11. 33 CFR 150.720 - What are the requirements for sound signals?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false What are the requirements for sound signals? 150.720 Section 150.720 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... are the requirements for sound signals? The sound signal on each pumping platform complex must...

  12. 49 CFR 236.12 - Spring switch signal protection; where required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch...

  13. 49 CFR 236.12 - Spring switch signal protection; where required.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch...

  14. 47 CFR 11.52 - EAS code and Attention Signal Monitoring requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS code and Attention Signal Monitoring... SYSTEM (EAS) Emergency Operations § 11.52 EAS code and Attention Signal Monitoring requirements. (a) EAS Participants must be capable of receiving the Attention Signal required by § 11.32(a)(9) and emergency...

  15. 49 CFR 236.12 - Spring switch signal protection; where required.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch...

  16. 49 CFR 236.12 - Spring switch signal protection; where required.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch...

  17. 49 CFR 236.12 - Spring switch signal protection; where required.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Spring switch signal protection; where required... Rules and Instructions: All Systems General § 236.12 Spring switch signal protection; where required. Signal protection shall be provided for facing and trailing movements through spring switch...

  18. Auditory adaptation improves tactile frequency perception.

    PubMed

    Crommett, Lexi E; Pérez-Bellido, Alexis; Yau, Jeffrey M

    2017-01-11

    Our ability to process temporal frequency information by touch underlies our capacity to perceive and discriminate surface textures. Auditory signals, which also provide extensive temporal frequency information, can systematically alter the perception of vibrations on the hand. How auditory signals shape tactile processing is unclear: perceptual interactions between contemporaneous sounds and vibrations are consistent with multiple neural mechanisms. Here we used a crossmodal adaptation paradigm, which separated auditory and tactile stimulation in time, to test the hypothesis that tactile frequency perception depends on neural circuits that also process auditory frequency. We reasoned that auditory adaptation effects would transfer to touch only if signals from both senses converge on common representations. We found that auditory adaptation can improve tactile frequency discrimination thresholds. This occurred only when adaptor and test frequencies overlapped. In contrast, auditory adaptation did not influence tactile intensity judgments. Thus, auditory adaptation enhances touch in a frequency- and feature-specific manner. A simple network model in which tactile frequency information is decoded from sensory neurons that are susceptible to auditory adaptation recapitulates these behavioral results. Our results imply that the neural circuits supporting tactile frequency perception also process auditory signals. This finding is consistent with the notion of supramodal operators performing canonical operations, like temporal frequency processing, regardless of input modality.

  19. 47 CFR 11.52 - EAS code and Attention Signal Monitoring requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... requirements. 11.52 Section 11.52 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Emergency Operations § 11.52 EAS code and Attention Signal Monitoring requirements. (a) EAS Participants must be capable of receiving the Attention Signal required by § 11.31(a)(2) and emergency messages...

  20. 47 CFR 80.753 - Signal strength requirements at the service area contour.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Signal strength requirements at the service... Station VHF Coverage § 80.753 Signal strength requirements at the service area contour. (a) The requirements for reception by a marine VHF shipboard receiver are satisfied if the field strength from...

  1. Minimal Requirements for the Emergence of Learned Signaling

    ERIC Educational Resources Information Center

    Spike, Matthew; Stadler, Kevin; Kirby, Simon; Smith, Kenny

    2017-01-01

    The emergence of signaling systems has been observed in numerous experimental and real-world contexts, but there is no consensus on which (if any) shared mechanisms underlie such phenomena. A number of explanatory mechanisms have been proposed within several disciplines, all of which have been instantiated as credible working models. However, they…

  2. Ca2+ Signaling During Mammalian Fertilization: Requirements, Players, and Adaptations

    PubMed Central

    Wakai, Takuya; Vanderheyden, Veerle; Fissore, Rafael A.

    2011-01-01

    Changes in the intracellular concentration of calcium ([Ca2+]i) represent a vital signaling mechanism enabling communication among cells and between cells and the environment. The initiation of embryo development depends on a [Ca2+]i increase(s) in the egg, which is generally induced during fertilization. The [Ca2+]i increase signals egg activation, which is the first stage in embryo development, and that consist of biochemical and structural changes that transform eggs into zygotes. The spatiotemporal patterns of [Ca2+]i at fertilization show variability, most likely reflecting adaptations to fertilizing conditions and to the duration of embryonic cell cycles. In mammals, the focus of this review, the fertilization [Ca2+]i signal displays unique properties in that it is initiated after gamete fusion by release of a sperm-derived factor and by periodic and extended [Ca2+]i responses. Here, we will discuss the events of egg activation regulated by increases in [Ca2+]i, the possible downstream targets that effect these egg activation events, and the property and identity of molecules both in sperm and eggs that underpin the initiation and persistence of the [Ca2+]i responses in these species. PMID:21441584

  3. The Drosophila Auditory System

    PubMed Central

    Boekhoff-Falk, Grace; Eberl, Daniel F.

    2013-01-01

    Development of a functional auditory system in Drosophila requires specification and differentiation of the chordotonal sensilla of Johnston’s organ (JO) in the antenna, correct axonal targeting to the antennal mechanosensory and motor center (AMMC) in the brain, and synaptic connections to neurons in the downstream circuit. Chordotonal development in JO is functionally complicated by structural, molecular and functional diversity that is not yet fully understood, and construction of the auditory neural circuitry is only beginning to unfold. Here we describe our current understanding of developmental and molecular mechanisms that generate the exquisite functions of the Drosophila auditory system, emphasizing recent progress and highlighting important new questions arising from research on this remarkable sensory system. PMID:24719289

  4. Filamin repeat segments required for photosensory signalling in Dictyostelium discoideum

    PubMed Central

    Annesley, Sarah J; Bandala-Sanchez, Esther; Ahmed, Afsar U; Fisher, Paul R

    2007-01-01

    Background Filamin is an actin binding protein which is ubiquitous in eukaryotes and its basic structure is well conserved – an N-terminal actin binding domain followed by a series of repeated segments which vary in number in different organisms. D. discoideum is a well established model organism for the study of signalling pathways and the actin cytoskeleton and as such makes an excellent organism in which to study filamin. Ddfilamin plays a putative role as a scaffolding protein in a photosensory signalling pathway and this role is thought to be mediated by the unusual repeat segments in the rod domain. Results To study the role of filamin in phototaxis, a filamin null mutant, HG1264, was transformed with constructs each of which expressed wild type filamin or a mutant filamin with a deletion of one of the repeat segments. Transformants expressing the full length filamin to wild type levels completely rescued the phototaxis defect in HG1264, however if filamin was expressed at lower than wild type levels the phototaxis defect was not restored. The transformants lacking any one of the repeat segments 2–6 retained defective phototaxis and thermotaxis phenotypes, whereas transformants expressing filaminΔ1 exhibited a range of partial complementation of the phototaxis phenotype which was related to expression levels. Immunofluorescence microscopy showed that filamin lacking any of the repeat segments still localised to the same actin rich areas as wild type filamin. Ddfilamin interacts with RasD and IP experiments demonstrated that this interaction did not rely upon any single repeat segment or the actin binding domain. Conclusion This paper demonstrates that wild type levels of filamin expression are essential for the formation of functional photosensory signalling complexes and that each of the repeat segments 2–6 are essential for filamins role in phototaxis. By contrast, repeat segment 1 is not essential provided the mutated filamin lacking repeat segment

  5. Auditory Processing Disorder (For Parents)

    MedlinePlus

    ... or other speech-language difficulties? Are verbal (word) math problems difficult for your child? Is your child ... inferences from conversations, understanding riddles, or comprehending verbal math problems — require heightened auditory processing and language levels. ...

  6. Spatiotemporal Relationships among Audiovisual Stimuli Modulate Auditory Facilitation of Visual Target Discrimination.

    PubMed

    Li, Qi; Yang, Huamin; Sun, Fang; Wu, Jinglong

    2015-03-01

    Sensory information is multimodal; through audiovisual interaction, task-irrelevant auditory stimuli tend to speed response times and increase visual perception accuracy. However, mechanisms underlying these performance enhancements have remained unclear. We hypothesize that task-irrelevant auditory stimuli might provide reliable temporal and spatial cues for visual target discrimination and behavioral response enhancement. Using signal detection theory, the present study investigated the effects of spatiotemporal relationships on auditory facilitation of visual target discrimination. Three experiments were conducted where an auditory stimulus maintained reliable temporal and/or spatial relationships with visual target stimuli. Results showed that perception sensitivity (d') to visual target stimuli was enhanced only when a task-irrelevant auditory stimulus maintained reliable spatiotemporal relationships with a visual target stimulus. When only reliable spatial or temporal information was contained, perception sensitivity was not enhanced. These results suggest that reliable spatiotemporal relationships between visual and auditory signals are required for audiovisual integration during a visual discrimination task, most likely due to a spread of attention. These results also indicate that auditory facilitation of visual target discrimination follows from late-stage cognitive processes rather than early stage sensory processes.

  7. 33 CFR 149.585 - What are the requirements for sound signals?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sound signals? 149.585 Section 149.585 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Navigation Miscellaneous § 149.585 What are the requirements for sound signals? (a) Each pumping platform complex must have a sound signal, approved under subpart 67.10 of this chapter, that has a 2-mile...

  8. 33 CFR 149.585 - What are the requirements for sound signals?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... sound signals? 149.585 Section 149.585 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Navigation Miscellaneous § 149.585 What are the requirements for sound signals? (a) Each pumping platform complex must have a sound signal, approved under subpart 67.10 of this chapter, that has a 2-mile...

  9. 33 CFR 149.585 - What are the requirements for sound signals?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sound signals? 149.585 Section 149.585 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Navigation Miscellaneous § 149.585 What are the requirements for sound signals? (a) Each pumping platform complex must have a sound signal, approved under subpart 67.10 of this chapter, that has a 2-mile...

  10. 33 CFR 149.585 - What are the requirements for sound signals?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... sound signals? 149.585 Section 149.585 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Navigation Miscellaneous § 149.585 What are the requirements for sound signals? (a) Each pumping platform complex must have a sound signal, approved under subpart 67.10 of this chapter, that has a 2-mile...

  11. 33 CFR 149.585 - What are the requirements for sound signals?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... sound signals? 149.585 Section 149.585 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Navigation Miscellaneous § 149.585 What are the requirements for sound signals? (a) Each pumping platform complex must have a sound signal, approved under subpart 67.10 of this chapter, that has a 2-mile...

  12. 49 CFR 236.204 - Track signaled for movements in both directions, requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... directions, requirements. On track signaled for movements in both directions, a train shall cause one or more... stopping distance apart for movements in one direction only, signals arranged to display restrictive... spaced less than stopping distance apart for movements in one direction, signals arranged to display...

  13. Nematode CLE signaling in Arabidopsis requires CLAVATA2 and CORYNE

    USDA-ARS?s Scientific Manuscript database

    Plant-parasitic cyst nematodes secrete CLAVATA3 (CLV3)/ESR(CLE)-like effector proteins. These proteins have been shown to act as ligand mimics of plant CLE peptides and are required for successful nematode infection; however, the receptors for nematode CLE-like peptides have not been identified. Her...

  14. 47 CFR 80.753 - Signal strength requirements at the service area contour.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Signal strength requirements at the service area contour. 80.753 Section 80.753 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... Station VHF Coverage § 80.753 Signal strength requirements at the service area contour. (a)...

  15. 47 CFR 80.753 - Signal strength requirements at the service area contour.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Signal strength requirements at the service area contour. 80.753 Section 80.753 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... Station VHF Coverage § 80.753 Signal strength requirements at the service area contour. (a)...

  16. 47 CFR 80.753 - Signal strength requirements at the service area contour.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Signal strength requirements at the service area contour. 80.753 Section 80.753 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... Station VHF Coverage § 80.753 Signal strength requirements at the service area contour. (a)...

  17. 47 CFR 80.753 - Signal strength requirements at the service area contour.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Signal strength requirements at the service area contour. 80.753 Section 80.753 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... Station VHF Coverage § 80.753 Signal strength requirements at the service area contour. (a)...

  18. Early auditory enrichment with music enhances auditory discrimination learning and alters NR2B protein expression in rat auditory cortex.

    PubMed

    Xu, Jinghong; Yu, Liping; Cai, Rui; Zhang, Jiping; Sun, Xinde

    2009-01-03

    Previous studies have shown that the functional development of auditory system is substantially influenced by the structure of environmental acoustic inputs in early life. In our present study, we investigated the effects of early auditory enrichment with music on rat auditory discrimination learning. We found that early auditory enrichment with music from postnatal day (PND) 14 enhanced learning ability in auditory signal-detection task and in sound duration-discrimination task. In parallel, a significant increase was noted in NMDA receptor subunit NR2B protein expression in the auditory cortex. Furthermore, we found that auditory enrichment with music starting from PND 28 or 56 did not influence NR2B expression in the auditory cortex. No difference was found in the NR2B expression in the inferior colliculus (IC) between music-exposed and normal rats, regardless of when the auditory enrichment with music was initiated. Our findings suggest that early auditory enrichment with music influences NMDA-mediated neural plasticity, which results in enhanced auditory discrimination learning.

  19. Lexical Influences on Auditory Streaming

    PubMed Central

    Billig, Alexander J.; Davis, Matthew H.; Deeks, John M.; Monstrey, Jolijn; Carlyon, Robert P.

    2013-01-01

    Summary Biologically salient sounds, including speech, are rarely heard in isolation. Our brains must therefore organize the input arising from multiple sources into separate “streams” and, in the case of speech, map the acoustic components of the target signal onto meaning. These auditory and linguistic processes have traditionally been considered to occur sequentially and are typically studied independently [1, 2]. However, evidence that streaming is modified or reset by attention [3], and that lexical knowledge can affect reports of speech sound identity [4, 5], suggests that higher-level factors may influence perceptual organization. In two experiments, listeners heard sequences of repeated words or acoustically matched nonwords. After several presentations, they reported that the initial /s/ sound in each syllable formed a separate stream; the percept then fluctuated between the streamed and fused states in a bistable manner. In addition to measuring these verbal transformations, we assessed streaming objectively by requiring listeners to detect occasional targets—syllables containing a gap after the initial /s/. Performance was better when streaming caused the syllables preceding the target to transform from words into nonwords, rather than from nonwords into words. Our results show that auditory stream formation is influenced not only by the acoustic properties of speech sounds, but also by higher-level processes involved in recognizing familiar words. PMID:23891107

  20. Sensory Processing of Backward-Masking Signals in Children with Language-Learning Impairment as Assessed with the Auditory Brainstem Response.

    ERIC Educational Resources Information Center

    Marler, Jeffrey A.; Champlin, Craig A.

    2005-01-01

    The purpose of this study was to examine the possible contribution of sensory mechanisms to an auditory processing deficit shown by some children with language-learning impairment (LLI). Auditory brainstem responses (ABRs) were measured from 2 groups of school-aged (8-10 years) children. One group consisted of 10 children with LLI, and the other…

  1. Auditory system

    NASA Technical Reports Server (NTRS)

    Ades, H. W.

    1973-01-01

    The physical correlations of hearing, i.e. the acoustic stimuli, are reported. The auditory system, consisting of external ear, middle ear, inner ear, organ of Corti, basilar membrane, hair cells, inner hair cells, outer hair cells, innervation of hair cells, and transducer mechanisms, is discussed. Both conductive and sensorineural hearing losses are also examined.

  2. Auditory system

    NASA Technical Reports Server (NTRS)

    Ades, H. W.

    1973-01-01

    The physical correlations of hearing, i.e. the acoustic stimuli, are reported. The auditory system, consisting of external ear, middle ear, inner ear, organ of Corti, basilar membrane, hair cells, inner hair cells, outer hair cells, innervation of hair cells, and transducer mechanisms, is discussed. Both conductive and sensorineural hearing losses are also examined.

  3. Copper is required for oncogenic BRAF signaling and tumorigenesis

    PubMed Central

    Brady, Donita C.; Crowe, Matthew S.; Turski, Michelle L.; Hobbs, G. Aaron; Yao, Xiaojie; Chaikuad, Apirat; Knapp, Stefan; Xiao, Kunhong; Campbell, Sharon L.; Thiele, Dennis J.; Counter, Christopher M.

    2014-01-01

    The BRAF kinase is mutated, typically V600E, to induce an active oncogenic state in a large fraction of melanoma, thyroid, hairy cell leukemia, and to a lesser extent, a wide spectrum of other cancers1,2. BRAFV600E phosphorylates and activates the kinases MEK1 and MEK2, which in turn phosphorylate and activate the kinases ERK1 and ERK2, stimulating the MAPK pathway to promote cancer3. Targeting MEK1/2 is proving to be an important therapeutic strategy, as a MEK1/2 inhibitor provides a survival advantage in metastatic melanoma4, which is increased when co-administered with a BRAFV600E inhibitor5. In this regard, we previously found that copper (Cu) influx enhances MEK1 phosphorylation of ERK1/2 through a Cu-MEK1 interaction6. We now show that genetic loss of the high affinity Cu transporter Ctr1 or mutations in MEK1 that disrupt Cu binding reduced BRAFV600E-driven signaling and tumorigenesis. Conversely, a MEK1-MEK5 chimera that phosphorylates ERK1/2 independent of Cu or an active ERK2 restored tumor growth to cells lacking Ctr1. Importantly, Cu chelators used in the treatment of Wilson disease7 reduced tumor growth of both BRAFV600E-transformed cells and cells resistant to BRAF inhibition. Taken together, these results suggest that Cu-chelation therapy could be repurposed to treat BRAFV600E mutation-positive cancers. PMID:24717435

  4. Auditory and visual differences in time perception? An investigation from a developmental perspective with neuropsychological tests.

    PubMed

    Zélanti, Pierre S; Droit-Volet, Sylvie

    2012-07-01

    Adults and children (5- and 8-year-olds) performed a temporal bisection task with either auditory or visual signals and either a short (0.5-1.0s) or long (4.0-8.0s) duration range. Their working memory and attentional capacities were assessed by a series of neuropsychological tests administered in both the auditory and visual modalities. Results showed an age-related improvement in the ability to discriminate time regardless of the sensory modality and duration. However, this improvement was seen to occur more quickly for auditory signals than for visual signals and for short durations rather than for long durations. The younger children exhibited the poorest ability to discriminate time for long durations presented in the visual modality. Statistical analyses of the neuropsychological scores revealed that an increase in working memory and attentional capacities in the visuospatial modality was the best predictor of age-related changes in temporal bisection performance for both visual and auditory stimuli. In addition, the poorer time sensitivity for visual stimuli than for auditory stimuli, especially in the younger children, was explained by the fact that the temporal processing of visual stimuli requires more executive attention than that of auditory stimuli. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Selective attention and the auditory vertex potential. I - Effects of stimulus delivery rate. II - Effects of signal intensity and masking noise

    NASA Technical Reports Server (NTRS)

    Schwent, V. L.; Hillyard, S. A.; Galambos, R.

    1976-01-01

    The effects of varying the rate of delivery of dichotic tone pip stimuli on selective attention measured by evoked-potential amplitudes and signal detectability scores were studied. The subjects attended to one channel (ear) of tones, ignored the other, and pressed a button whenever occasional targets - tones of a slightly higher pitch were detected in the attended ear. Under separate conditions, randomized interstimulus intervals were short, medium, and long. Another study compared the effects of attention on the N1 component of the auditory evoked potential for tone pips presented alone and when white noise was added to make the tones barely above detectability threshold in a three-channel listening task. Major conclusions are that (1) N1 is enlarged to stimuli in an attended channel only in the short interstimulus interval condition (averaging 350 msec), (2) N1 and P3 are related to different modes of selective attention, and (3) attention selectivity in multichannel listening task is greater when tones are faint and/or difficult to detect.

  6. Selective attention and the auditory vertex potential. I - Effects of stimulus delivery rate. II - Effects of signal intensity and masking noise

    NASA Technical Reports Server (NTRS)

    Schwent, V. L.; Hillyard, S. A.; Galambos, R.

    1976-01-01

    The effects of varying the rate of delivery of dichotic tone pip stimuli on selective attention measured by evoked-potential amplitudes and signal detectability scores were studied. The subjects attended to one channel (ear) of tones, ignored the other, and pressed a button whenever occasional targets - tones of a slightly higher pitch were detected in the attended ear. Under separate conditions, randomized interstimulus intervals were short, medium, and long. Another study compared the effects of attention on the N1 component of the auditory evoked potential for tone pips presented alone and when white noise was added to make the tones barely above detectability threshold in a three-channel listening task. Major conclusions are that (1) N1 is enlarged to stimuli in an attended channel only in the short interstimulus interval condition (averaging 350 msec), (2) N1 and P3 are related to different modes of selective attention, and (3) attention selectivity in multichannel listening task is greater when tones are faint and/or difficult to detect.

  7. Brain Dynamics of Aging: Multiscale Variability of EEG Signals at Rest and during an Auditory Oddball Task1,2,3

    PubMed Central

    Sleimen-Malkoun, Rita; Perdikis, Dionysios; Müller, Viktor; Blanc, Jean-Luc; Huys, Raoul; Temprado, Jean-Jacques

    2015-01-01

    Abstract The present work focused on the study of fluctuations of cortical activity across time scales in young and older healthy adults. The main objective was to offer a comprehensive characterization of the changes of brain (cortical) signal variability during aging, and to make the link with known underlying structural, neurophysiological, and functional modifications, as well as aging theories. We analyzed electroencephalogram (EEG) data of young and elderly adults, which were collected at resting state and during an auditory oddball task. We used a wide battery of metrics that typically are separately applied in the literature, and we compared them with more specific ones that address their limits. Our procedure aimed to overcome some of the methodological limitations of earlier studies and verify whether previous findings can be reproduced and extended to different experimental conditions. In both rest and task conditions, our results mainly revealed that EEG signals presented systematic age-related changes that were time-scale-dependent with regard to the structure of fluctuations (complexity) but not with regard to their magnitude. Namely, compared with young adults, the cortical fluctuations of the elderly were more complex at shorter time scales, but less complex at longer scales, although always showing a lower variance. Additionally, the elderly showed signs of spatial, as well as between, experimental conditions dedifferentiation. By integrating these so far isolated findings across time scales, metrics, and conditions, the present study offers an overview of age-related changes in the fluctuation electrocortical activity while making the link with underlying brain dynamics. PMID:26464983

  8. Assessing effectiveness of various auditory warning signals in maintaining drivers' attention in virtual reality-based driving environments.

    PubMed

    Lin, Chin-Teng; Chiu, Tien-Ting; Huang, Teng-Yi; Chao, Chih-Feng; Liang, Wen-Chieh; Hsu, Shang-Hwa; Ko, Li-Wei

    2009-06-01

    Drivers' fatigue contributes to traffic accidents, so drivers must maintain adequate alertness. The effectiveness of audio alarms in maintaining driving performance and characteristics of alarms was studied in a virtural reality-based driving environment. Response time to the car's drifting was measured under seven conditions: with no warnings and with continuous warning tones (500 Hz, 1750 Hz, and 3000 Hz), and with tone bursts at 500 Hz, 1750 Hz, and 3000 Hz. Analyses showed the audio warning signals significantly improved driving. Further, the tones' spectral characteristics significantly influenced the effectiveness of the warning.

  9. Sustainable Land Use Requires Attention to Ecological Signals

    USGS Publications Warehouse

    Halvorson, W.L.; Castellanos, A.E.; Murrieta-Saldivar, J.

    2003-01-01

    This case study details the difficulties of landscape management, highlighting the challenges inherent in managing natural resources when multiple agencies are involved, when the land users have no incentive for conservation, and when government agencies have too few resources for effective management. Pumping of groundwater from the aquifer of La Costa de Hermosillo in the state of Sonora, Mexico, began in 1945 and developed so quickly that by the late 1950s salinity intrusion from the Gulf of California was occurring in the wells. In the 1970s, the irrigatable land in La Costa peaked at 132,516 ha and the extracted volume of water from the aquifer peaked at around 1.14 billion cubic meters annually. By the 1980s, 105 wells of the total of 498 were contaminated with seawater and, therefore, identified for closure. At present La Costa de Hermosillo still represents 15% of the total harvested land, 16% of the total annual production, and 23% of the gross agricultural production of the state of Sonora. However, there are approximately 80,000 ha of abandoned fields due to salt water intension, lack of water and/or lack of credit available to individual farmers. This unstable situation resulted from the interplay of water management policies and practices, and farm-land policies and practices. While government agencies have been able to enforce better water use for agricultural production, there remains a significant area that requires restoration from its degraded state. For this piece of the ecosystem management puzzle, government agencies have thus far been unable to affect a solution.

  10. Auditory orientation in crickets: Pattern recognition controls reactive steering

    NASA Astrophysics Data System (ADS)

    Poulet, James F. A.; Hedwig, Berthold

    2005-10-01

    Many groups of insects are specialists in exploiting sensory cues to locate food resources or conspecifics. To achieve orientation, bees and ants analyze the polarization pattern of the sky, male moths orient along the females' odor plume, and cicadas, grasshoppers, and crickets use acoustic signals to locate singing conspecifics. In comparison with olfactory and visual orientation, where learning is involved, auditory processing underlying orientation in insects appears to be more hardwired and genetically determined. In each of these examples, however, orientation requires a recognition process identifying the crucial sensory pattern to interact with a localization process directing the animal's locomotor activity. Here, we characterize this interaction. Using a sensitive trackball system, we show that, during cricket auditory behavior, the recognition process that is tuned toward the species-specific song pattern controls the amplitude of auditory evoked steering responses. Females perform small reactive steering movements toward any sound patterns. Hearing the male's calling song increases the gain of auditory steering within 2-5 s, and the animals even steer toward nonattractive sound patterns inserted into the speciesspecific pattern. This gain control mechanism in the auditory-to-motor pathway allows crickets to pursue species-specific sound patterns temporarily corrupted by environmental factors and may reflect the organization of recognition and localization networks in insects. localization | phonotaxis

  11. Intact spectral but abnormal temporal processing of auditory stimuli in autism.

    PubMed

    Groen, Wouter B; van Orsouw, Linda; Huurne, Niels ter; Swinkels, Sophie; van der Gaag, Rutger-Jan; Buitelaar, Jan K; Zwiers, Marcel P

    2009-05-01

    The perceptual pattern in autism has been related to either a specific localized processing deficit or a pathway-independent, complexity-specific anomaly. We examined auditory perception in autism using an auditory disembedding task that required spectral and temporal integration. 23 children with high-functioning-autism and 23 matched controls participated. Participants were presented with two-syllable words embedded in various auditory backgrounds (pink noise, moving ripple, amplitude-modulated pink noise, amplitude-modulated moving ripple) to assess speech-in-noise-reception thresholds. The gain in signal perception of pink noise with temporal dips relative to pink noise without temporal dips was smaller in children with autism (p = 0.008). Thus, the autism group was less able to integrate auditory information present in temporal dips in background sound, supporting the complexity-specific perceptual account.

  12. 47 CFR 11.51 - EAS code and Attention Signal Transmission requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Message (EOM) codes using the EAS Protocol. The Attention Signal must precede any emergency audio message... audio messages. No Attention Signal is required for EAS messages that do not contain audio programming... EAS messages in the main audio channel. All DAB stations shall also transmit EAS messages on all audio...

  13. 47 CFR 11.51 - EAS code and Attention Signal Transmission requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Message (EOM) codes using the EAS Protocol. The Attention Signal must precede any emergency audio message... audio messages. No Attention Signal is required for EAS messages that do not contain audio programming... EAS messages in the main audio channel. All DAB stations shall also transmit EAS messages on all audio...

  14. Auditory short-term memory in the primate auditory cortex.

    PubMed

    Scott, Brian H; Mishkin, Mortimer

    2016-06-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ׳working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ׳match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory.

  15. A Model of Auditory-Cognitive Processing and Relevance to Clinical Applicability.

    PubMed

    Edwards, Brent

    2016-01-01

    Hearing loss and cognitive function interact in both a bottom-up and top-down relationship. Listening effort is tied to these interactions, and models have been developed to explain their relationship. The Ease of Language Understanding model in particular has gained considerable attention in its explanation of the effect of signal distortion on speech understanding. Signal distortion can also affect auditory scene analysis ability, however, resulting in a distorted auditory scene that can affect cognitive function, listening effort, and the allocation of cognitive resources. These effects are explained through an addition to the Ease of Language Understanding model. This model can be generalized to apply to all sounds, not only speech, representing the increased effort required for auditory environmental awareness and other nonspeech auditory tasks. While the authors have measures of speech understanding and cognitive load to quantify these interactions, they are lacking measures of the effect of hearing aid technology on auditory scene analysis ability and how effort and attention varies with the quality of an auditory scene. Additionally, the clinical relevance of hearing aid technology on cognitive function and the application of cognitive measures in hearing aid fittings will be limited until effectiveness is demonstrated in real-world situations.

  16. Synchronizing to real events: Subjective audiovisual alignment scales with perceived auditory depth and speed of sound

    PubMed Central

    Alais, David; Carlile, Simon

    2005-01-01

    Because of the slow speed of sound relative to light, acoustic and visual signals from a distant event often will be received asynchronously. Here, using acoustic signals with a robust cue to sound source distance, we show that judgments of perceived temporal alignment with a visual marker depend on the depth simulated in the acoustic signal. For distant sounds, a large delay of sound relative to vision is required for the signals to be perceived as temporally aligned. For nearer sources, the time lag corresponding to audiovisual alignment is smaller and scales at rate approximating the speed of sound. Thus, when robust cues to auditory distance are present, the brain can synchronize disparate audiovisual signals to external events despite considerable differences in time of arrival at the perceiver. This ability is functionally important as it allows auditory and visual signals to be synchronized to the external event that caused them. PMID:15668388

  17. Synchronizing to real events: subjective audiovisual alignment scales with perceived auditory depth and speed of sound.

    PubMed

    Alais, David; Carlile, Simon

    2005-02-08

    Because of the slow speed of sound relative to light, acoustic and visual signals from a distant event often will be received asynchronously. Here, using acoustic signals with a robust cue to sound source distance, we show that judgments of perceived temporal alignment with a visual marker depend on the depth simulated in the acoustic signal. For distant sounds, a large delay of sound relative to vision is required for the signals to be perceived as temporally aligned. For nearer sources, the time lag corresponding to audiovisual alignment is smaller and scales at rate approximating the speed of sound. Thus, when robust cues to auditory distance are present, the brain can synchronize disparate audiovisual signals to external events despite considerable differences in time of arrival at the perceiver. This ability is functionally important as it allows auditory and visual signals to be synchronized to the external event that caused them.

  18. [Auditory fatigue].

    PubMed

    Sanjuán Juaristi, Julio; Sanjuán Martínez-Conde, Mar

    2015-01-01

    Given the relevance of possible hearing losses due to sound overloads and the short list of references of objective procedures for their study, we provide a technique that gives precise data about the audiometric profile and recruitment factor. Our objectives were to determine peripheral fatigue, through the cochlear microphonic response to sound pressure overload stimuli, as well as to measure recovery time, establishing parameters for differentiation with regard to current psychoacoustic and clinical studies. We used specific instruments for the study of cochlear microphonic response, plus a function generator that provided us with stimuli of different intensities and harmonic components. In Wistar rats, we first measured the normal microphonic response and then the effect of auditory fatigue on it. Using a 60dB pure tone acoustic stimulation, we obtained a microphonic response at 20dB. We then caused fatigue with 100dB of the same frequency, reaching a loss of approximately 11dB after 15minutes; after that, the deterioration slowed and did not exceed 15dB. By means of complex random tone maskers or white noise, no fatigue was caused to the sensory receptors, not even at levels of 100dB and over an hour of overstimulation. No fatigue was observed in terms of sensory receptors. Deterioration of peripheral perception through intense overstimulation may be due to biochemical changes of desensitisation due to exhaustion. Auditory fatigue in subjective clinical trials presumably affects supracochlear sections. The auditory fatigue tests found are not in line with those obtained subjectively in clinical and psychoacoustic trials. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  19. The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal transduction pathway.

    PubMed Central

    Biggs, W H; Zavitz, K H; Dickson, B; van der Straten, A; Brunner, D; Hafen, E; Zipursky, S L

    1994-01-01

    Mitogen-activated protein (MAP) kinases have been proposed to play a critical role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways. Although genetic and biochemical studies of RTK pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals have revealed remarkable similarities, a genetic requirement for MAP kinases in RTK signaling has not been established. During retinal development in Drosophila, the sevenless (Sev) RTK is required for development of the R7 photoreceptor cell. Components of the signal transduction pathway activated by Sev in the R7 precursor include proteins encoded by the gap1, drk, Sos, ras1 and raf loci. In this report we present evidence that a Drosophila MAP kinase, ERK-A, is encoded by the rolled locus and is required downstream of raf in the Sev signal transduction pathway. Images PMID:8157002

  20. Two Adjacent Trimeric Fas Ligands Are Required for Fas Signaling and Formation of a Death-Inducing Signaling Complex

    PubMed Central

    Holler, Nils; Tardivel, Aubry; Kovacsovics-Bankowski, Magdalena; Hertig, Sylvie; Gaide, Olivier; Martinon, Fabio; Tinel, Antoine; Deperthes, David; Calderara, Silvio; Schulthess, Therese; Engel, Jürgen; Schneider, Pascal; Tschopp, Jürg

    2003-01-01

    The membrane-bound form of Fas ligand (FasL) signals apoptosis in target cells through engagement of the death receptor Fas, whereas the proteolytically processed, soluble form of FasL does not induce cell death. However, soluble FasL can be rendered active upon cross-linking. Since the minimal extent of oligomerization of FasL that exerts cytotoxicity is unknown, we engineered hexameric proteins containing two trimers of FasL within the same molecule. This was achieved by fusing FasL to the Fc portion of immunoglobulin G1 or to the collagen domain of ACRP30/adiponectin. Trimeric FasL and hexameric FasL both bound to Fas, but only the hexameric forms were highly cytotoxic and competent to signal apoptosis via formation of a death-inducing signaling complex. Three sequential early events in Fas-mediated apoptosis could be dissected, namely, receptor binding, receptor activation, and recruitment of intracellular signaling molecules, each of which occurred independently of the subsequent one. These results demonstrate that the limited oligomerization of FasL, and most likely of some other tumor necrosis factor family ligands such as CD40L, is required for triggering of the signaling pathways. PMID:12556501

  1. Endogenous VMH amylin signaling is required for full leptin signaling and protection from diet-induced obesity.

    PubMed

    Dunn-Meynell, Ambrose A; Le Foll, Christelle; Johnson, Miranda D; Lutz, Thomas A; Hayes, Matthew R; Levin, Barry E

    2016-02-15

    Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling and synergistically reduces food intake and body weight in selectively bred diet-induced obese (DIO) rats. Since DIO (125)I-amylin dorsomedial nucleus-dorsomedial VMN binding was reduced, we postulated that this contributed to DIO ventromedial hypothalamus (VMH) leptin resistance, and that impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated signaling by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA would predispose diet-resistant (DR) rats to obesity on high-fat (45%) diet (HFD). Depleting VMH CTR by 80-90% in 4-wk-old male DR rats reduced their ARC and VMN (125)I-labeled leptin binding by 57 and 51%, respectively, and VMN leptin-induced phospho-signal transducer and activator of transcription 3-positive neurons by 59% vs. AAV control rats. After 6 wk on chow, VMH CTR-depleted DR rats ate and gained the equivalent amount of food and weight but had 18% heavier fat pads (relative to carcass weight), 144% higher leptin levels, and were insulin resistant compared with control AAV DR rats. After 6 wk more on HFD, VMH CTR-depleted DR rats ate the same amount but gained 28% more weight, had 60% more carcass fat, 254% higher leptin levels, and 132% higher insulin areas under the curve during an oral glucose tolerance test than control DR rats. Therefore, impairing endogenous VMH CTR-mediated signaling reduced leptin signaling and caused DR rats to become more obese and insulin resistant, both on chow and HFD. These results suggest that endogenous VMH amylin signaling is required for full leptin signaling and protection from HFD-induced obesity.

  2. Endogenous VMH amylin signaling is required for full leptin signaling and protection from diet-induced obesity

    PubMed Central

    Dunn-Meynell, Ambrose A.; Le Foll, Christelle; Johnson, Miranda D.; Lutz, Thomas A.; Hayes, Matthew R.

    2015-01-01

    Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling and synergistically reduces food intake and body weight in selectively bred diet-induced obese (DIO) rats. Since DIO 125I-amylin dorsomedial nucleus-dorsomedial VMN binding was reduced, we postulated that this contributed to DIO ventromedial hypothalamus (VMH) leptin resistance, and that impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated signaling by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA would predispose diet-resistant (DR) rats to obesity on high-fat (45%) diet (HFD). Depleting VMH CTR by 80–90% in 4-wk-old male DR rats reduced their ARC and VMN 125I-labeled leptin binding by 57 and 51%, respectively, and VMN leptin-induced phospho-signal transducer and activator of transcription 3-positive neurons by 59% vs. AAV control rats. After 6 wk on chow, VMH CTR-depleted DR rats ate and gained the equivalent amount of food and weight but had 18% heavier fat pads (relative to carcass weight), 144% higher leptin levels, and were insulin resistant compared with control AAV DR rats. After 6 wk more on HFD, VMH CTR-depleted DR rats ate the same amount but gained 28% more weight, had 60% more carcass fat, 254% higher leptin levels, and 132% higher insulin areas under the curve during an oral glucose tolerance test than control DR rats. Therefore, impairing endogenous VMH CTR-mediated signaling reduced leptin signaling and caused DR rats to become more obese and insulin resistant, both on chow and HFD. These results suggest that endogenous VMH amylin signaling is required for full leptin signaling and protection from HFD-induced obesity. PMID:26676252

  3. Functional Organization of the Ventral Auditory Pathway.

    PubMed

    Cohen, Yale E; Bennur, Sharath; Christison-Lagay, Kate; Gifford, Adam M; Tsunada, Joji

    2016-01-01

    The fundamental problem in audition is determining the mechanisms required by the brain to transform an unlabelled mixture of auditory stimuli into coherent perceptual representations. This process is called auditory-scene analysis. The perceptual representations that result from auditory-scene analysis are formed through a complex interaction of perceptual grouping, attention, categorization and decision-making. Despite a great deal of scientific energy devoted to understanding these aspects of hearing, we still do not understand (1) how sound perception arises from neural activity and (2) the causal relationship between neural activity and sound perception. Here, we review the role of the "ventral" auditory pathway in sound perception. We hypothesize that, in the early parts of the auditory cortex, neural activity reflects the auditory properties of a stimulus. However, in latter parts of the auditory cortex, neurons encode the sensory evidence that forms an auditory decision and are causally involved in the decision process. Finally, in the prefrontal cortex, which receives input from the auditory cortex, neural activity reflects the actual perceptual decision. Together, these studies indicate that the ventral pathway contains hierarchical circuits that are specialized for auditory perception and scene analysis.

  4. Auditory color constancy

    NASA Astrophysics Data System (ADS)

    Kluender, Keith R.; Kiefte, Michael

    2003-10-01

    It is both true and efficient that sensorineural systems respond to change and little else. Perceptual systems do not record absolute level be it loudness, pitch, brightness, or color. This fact has been demonstrated in every sensory domain. For example, the visual system is remarkable at maintaining color constancy over widely varying illumination such as sunlight and varieties of artificial light (incandescent, fluorescent, etc.) for which spectra reflected from objects differ dramatically. Results will be reported for a series of experiments demonstrating how auditory systems similarly compensate for reliable characteristics of spectral shape in acoustic signals. Specifically, listeners' perception of vowel sounds, characterized by both local (e.g., formants) and broad (e.g., tilt) spectral composition, changes radically depending upon reliable spectral composition of precursor signals. These experiments have been conducted using a variety of precursor signals consisting of meaningful and time-reversed vocoded sentences, as well as novel nonspeech precursors consisting of multiple filter poles modulating sinusoidally across a source spectrum with specific local and broad spectral characteristics. Constancy across widely varying spectral compositions shares much in common with visual color constancy. However, auditory spectral constancy appears to be more effective than visual constancy in compensating for local spectral fluctuations. [Work supported by NIDCD DC-04072.

  5. The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling.

    PubMed

    Das, P; Maduzia, L L; Wang, H; Finelli, A L; Cho, S H; Smith, M M; Padgett, R W

    1998-04-01

    Signals from transforming growth factor-beta (TGF-beta) ligands are transmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previous identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a general feature of TGF-beta signaling. We report here the identification of a new Drosophila class II Smad, Medea, a close homolog of the human tumor-suppressor gene DPC4. Embryos from germline clones of both Medea and Mad (a class I Smad) are ventralized, as are embryos null for the TGF-beta-like ligand decapentaplegic (dpp). Loss of Medea also blocks dpp signaling during later development, suggesting that Medea, like Mad, is universally required for dpp signaling. Furthermore, we show that the necessity for these two closely related, non-redundant Smads, is due to their different signaling properties - upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus. These results provide a paradigm for, and distinguish between, the requirement for class I and II Smads in Dpp/BMP signaling.

  6. Early neural crest induction requires an initial inhibition of Wnt signals.

    PubMed

    Steventon, Ben; Mayor, Roberto

    2012-05-01

    Neural crest (NC) induction is a long process that continues through gastrula and neurula stages. In order to reveal additional stages of NC induction we performed a series of explants where different known inducing tissues were taken along with the prospective NC. Interestingly the dorso-lateral marginal zone (DLMZ) is only able to promote the expression of a subset of neural plate border (NPB) makers without the presence of specific NC markers. We then analysed the temporal requirement for BMP and Wnt signals for the NPB genes Hairy2a and Dlx5, compared to the expression of neural plate (NP) and NC genes. Although the NP is sensitive to BMP levels at early gastrula stages, Hairy2a/Dlx5 expression is unaffected. Later, the NP becomes insensitive to BMP levels at late gastrulation when NC markers require an inhibition. The NP requires an inhibition of Wnt signals prior to gastrulation, but becomes insensitive during early gastrula stages when Hairy2a/Dlx5 requires an inhibition of Wnt signalling. An increase in Wnt signalling is then important for the switch from NPB to NC at late gastrula stages. In addition to revealing an additional distinct signalling event in NC induction, this work emphasizes the importance of integrating both timing and levels of signalling activity during the patterning of complex tissues such as the vertebrate ectoderm.

  7. Wnt/β-catenin signaling in dermal condensates is required for hair follicle formation

    PubMed Central

    Tsai, Su-Yi; Sennett, Rachel; Rezza, Amélie; Clavel, Carlos; Grisanti, Laura; Zemla, Roland; Najam, Sara; Rendl, Michael

    2014-01-01

    Broad dermal Wnt signaling is required for patterned induction of hair follicle placodes and subsequent Wnt signaling in placode stem cells is essential for induction of dermal condensates, cell clusters of precursors for the hair follicle dermal papilla (DP). Progression of hair follicle formation then requires coordinated signal exchange between dermal condensates and placode stem cells. However, it remains unknown whether continued Wnt signaling in DP precursor cells plays a role in this process, largely due to the long-standing inability to specifically target dermal condensates for gene ablation. Here we use the Tbx18Cre knockin mouse line to ablate the Wnt-responsive transcription factor β-catenin specifically in these cells at E14.5 during the first wave of guard hair follicle formation. In the absence of β-catenin, canonical Wnt signaling is effectively abolished in these cells. Sox2+ dermal condensates initiate normally, however by E16.5 guard hair follicle numbers are strongly reduced and by E18.5 most whiskers and guard hair follicles are absent, suggesting that active Wnt signaling in dermal condensates is important for hair follicle formation to proceed after induction. To explore the molecular mechanisms by which Wnt signaling in dermal condensates regulates hair follicle formation, we analyze genome-wide the gene expression changes in embryonic β-catenin null DP precursor cells. We find altered expression of several signaling pathway genes, including Fgfs and Activin, both previously implicated in hair follicle formation. In summary, these data reveal a functional role of Wnt signaling in DP precursors for embryonic hair follicle formation and identify Fgf and Activin signaling as potential effectors of Wnt signaling-regulated events. PMID:24309208

  8. Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells.

    PubMed

    Yang, Pei-Tzu; Lorenowicz, Magdalena J; Silhankova, Marie; Coudreuse, Damien Y M; Betist, Marco C; Korswagen, Hendrik C

    2008-01-01

    Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. We have previously shown that Wnt signaling requires retromer function in Wnt-producing cells. The retromer is a multiprotein complex that mediates endosome-to-Golgi transport of specific sorting receptors. MIG-14/Wls is a conserved transmembrane protein that binds Wnt and is required in Wnt-producing cells for Wnt secretion. Here, we demonstrate that in the absence of retromer function, MIG-14/Wls is degraded in lysosomes and becomes limiting for Wnt signaling. We show that retromer-dependent recycling of MIG-14/Wls is part of a trafficking pathway that retrieves MIG-14/Wls from the plasma membrane. We propose that MIG-14/Wls cycles between the Golgi and the plasma membrane to mediate Wnt secretion. Regulation of this transport pathway may enable Wnt-producing cells to control the range of Wnt signaling in the tissue.

  9. Auditory short-term memory in the primate auditory cortex

    PubMed Central

    Scott, Brian H.; Mishkin, Mortimer

    2015-01-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ‘working memory’ bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ‘match’ stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. PMID:26541581

  10. Signaling required for blood vessel maintenance: molecular basis and pathological manifestations.

    PubMed

    Murakami, Masahiro

    2012-01-01

    As our understanding of molecular mechanisms leading to vascular formation increases, vessel maintenance including stabilization of new vessels and prevention of vessel regression began to be considered as an active process that requires specific cellular signaling. While signaling pathways such as VEGF, FGF, and angiopoietin-Tie2 are important for endothelial cell survival and junction stabilization, PDGF and TGF-β signaling modify mural cell (vascular smooth muscle cells and pericytes) functions, thus they fortify vessel integrity. Breakdown of these signaling systems results in pathological hyperpermeability and/or genetic vascular abnormalities such as vascular malformations, ultimately progressing to hemorrhage and edema. Hence, blood vessel maintenance is fundamental to controlling vascular homeostasis and tissue functions. This paper discusses signaling pathways essential for vascular maintenance and clinical conditions caused by deterioration of vessel integrity.

  11. DNA sequence and structure requirements for cleavage of V(D)J recombination signal sequences.

    PubMed Central

    Cuomo, C A; Mundy, C L; Oettinger, M A

    1996-01-01

    Purified RAG1 and RAG2 proteins can cleave DNA at V(D)J recombination signals. In dissecting the DNA sequence and structural requirements for cleavage, we find that the heptamer and nonamer motifs of the recombination signal sequence can independently direct both steps of the cleavage reaction. Proper helical spacing between these two elements greatly enhances the efficiency of cleavage, whereas improper spacing can lead to interference between the two elements. The signal sequences are surprisingly tolerant of structural variation and function efficiently when nicks, gaps, and mismatched bases are introduced or even when the signal sequence is completely single stranded. Sequence alterations that facilitate unpairing of the bases at the signal/coding border activate the cleavage reaction, suggesting that DNA distortion is critical for V(D)J recombination. PMID:8816481

  12. Improved long-term memory via enhancing cGMP-PKG signaling requires cAMP-PKA signaling.

    PubMed

    Bollen, Eva; Puzzo, Daniela; Rutten, Kris; Privitera, Lucia; De Vry, Jochen; Vanmierlo, Tim; Kenis, Gunter; Palmeri, Agostino; D'Hooge, Rudi; Balschun, Detlef; Steinbusch, Harry M W; Blokland, Arjan; Prickaerts, Jos

    2014-10-01

    Memory consolidation is defined by the stabilization of a memory trace after acquisition, and consists of numerous molecular cascades that mediate synaptic plasticity. Commonly, a distinction is made between an early and a late consolidation phase, in which early refers to the first hours in which labile synaptic changes occur, whereas late consolidation relates to stable and long-lasting synaptic changes induced by de novo protein synthesis. How these phases are linked at a molecular level is not yet clear. Here we studied the interaction of the cyclic nucleotide-mediated pathways during the different phases of memory consolidation in rodents. In addition, the same pathways were studied in a model of neuronal plasticity, long-term potentiation (LTP). We demonstrated that cGMP/protein kinase G (PKG) signaling mediates early memory consolidation as well as early-phase LTP, whereas cAMP/protein kinase A (PKA) signaling mediates late consolidation and late-phase-like LTP. In addition, we show for the first time that early-phase cGMP/PKG signaling requires late-phase cAMP/PKA-signaling in both LTP and long-term memory formation.

  13. Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

    PubMed Central

    Bollen, Eva; Puzzo, Daniela; Rutten, Kris; Privitera, Lucia; De Vry, Jochen; Vanmierlo, Tim; Kenis, Gunter; Palmeri, Agostino; D'Hooge, Rudi; Balschun, Detlef; Steinbusch, Harry MW; Blokland, Arjan; Prickaerts, Jos

    2014-01-01

    Memory consolidation is defined by the stabilization of a memory trace after acquisition, and consists of numerous molecular cascades that mediate synaptic plasticity. Commonly, a distinction is made between an early and a late consolidation phase, in which early refers to the first hours in which labile synaptic changes occur, whereas late consolidation relates to stable and long-lasting synaptic changes induced by de novo protein synthesis. How these phases are linked at a molecular level is not yet clear. Here we studied the interaction of the cyclic nucleotide-mediated pathways during the different phases of memory consolidation in rodents. In addition, the same pathways were studied in a model of neuronal plasticity, long-term potentiation (LTP). We demonstrated that cGMP/protein kinase G (PKG) signaling mediates early memory consolidation as well as early-phase LTP, whereas cAMP/protein kinase A (PKA) signaling mediates late consolidation and late-phase-like LTP. In addition, we show for the first time that early-phase cGMP/PKG signaling requires late-phase cAMP/PKA-signaling in both LTP and long-term memory formation. PMID:24813825

  14. Benign lesions of the external auditory canal.

    PubMed

    Tran, L P; Grundfast, K M; Selesnick, S H

    1996-10-01

    Benign mass lesions of the external auditory canal, such as exostoses and osteomas, are common findings on physical examination but most often do not require treatment. The differential diagnosis of lesions in the external auditory canal, however, should not be limited to those benign processes discussed here, but should also include infectious, dermatologic, congenital, and malignant processes.

  15. Differential requirement for BMP signaling in atrial and ventricular lineages establishes cardiac chamber proportionality

    PubMed Central

    Marques, Sara R.; Yelon, Deborah

    2009-01-01

    The function of an organ relies upon the proper relative proportions of its individual operational components. For example, effective embryonic circulation requires the appropriate relative sizes of each of the distinct pumps created by the atrial and ventricular cardiac chambers. Although the differences between atrial and ventricular cardiomyocytes are well established, little is known about the mechanisms regulating production of proportional numbers of each cell type. We find that mutation of the zebrafish type I BMP receptor gene alk8 causes reduction of atrial size without affecting the ventricle. Loss of atrial tissue is evident in the lateral mesoderm prior to heart tube formation and results from the inhibition of BMP signaling during cardiac progenitor specification stages. Comparison of the effects of decreased and increased BMP signaling further demonstrates that atrial cardiomyocyte production correlates with levels of BMP signaling while ventricular cardiomyocyte production is less susceptible to manipulation of BMP signaling. Additionally, mosaic analysis provides evidence for a cell-autonomous requirement for BMP signaling during cardiomyocyte formation and chamber fate assignment. Together, our studies uncover a new role for BMP signaling in the regulation of chamber size, supporting a model in which differential reception of cardiac inductive signals establishes chamber proportion. PMID:19232521

  16. Mesenchymal Bone Morphogenetic Protein Signaling Is Required for Normal Pancreas Development

    PubMed Central

    Ahnfelt-Rønne, Jonas; Ravassard, Philippe; Pardanaud-Glavieux, Corinne; Scharfmann, Raphaél; Serup, Palle

    2010-01-01

    OBJECTIVE Pancreas organogenesis is orchestrated by interactions between the epithelium and the mesenchyme, but these interactions are not completely understood. Here we investigated a role for bone morphogenetic protein (BMP) signaling within the pancreas mesenchyme and found it to be required for the normal development of the mesenchyme as well as for the pancreatic epithelium. RESEARCH DESIGN AND METHODS We analyzed active BMP signaling by immunostaining for phospho-Smad1,5,8 and tested whether pancreas development was affected by BMP inhibition after expression of Noggin and dominant negative BMP receptors in chicken and mouse pancreas. RESULTS Endogenous BMP signaling is confined to the mesenchyme in the early pancreas and inhibition of BMP signaling results in severe pancreatic hypoplasia with reduced epithelial branching. Notably, we also observed an excessive endocrine differentiation when mesenchymal BMP signaling is blocked, presumably secondary to defective mesenchyme to epithelium signaling. CONCLUSIONS We conclude that BMP signaling plays a previously unsuspected role in the mesenchyme, required for normal development of the mesenchyme as well as for the epithelium. PMID:20522595

  17. Low power adder based auditory filter architecture.

    PubMed

    Rahiman, P F Khaleelur; Jayanthi, V S

    2014-01-01

    Cochlea devices are powered up with the help of batteries and they should possess long working life to avoid replacing of devices at regular interval of years. Hence the devices with low power consumptions are required. In cochlea devices there are numerous filters, each responsible for frequency variant signals, which helps in identifying speech signals of different audible range. In this paper, multiplierless lookup table (LUT) based auditory filter is implemented. Power aware adder architectures are utilized to add the output samples of the LUT, available at every clock cycle. The design is developed and modeled using Verilog HDL, simulated using Mentor Graphics Model-Sim Simulator, and synthesized using Synopsys Design Compiler tool. The design was mapped to TSMC 65 nm technological node. The standard ASIC design methodology has been adapted to carry out the power analysis. The proposed FIR filter architecture has reduced the leakage power by 15% and increased its performance by 2.76%.

  18. Low Power Adder Based Auditory Filter Architecture

    PubMed Central

    Jayanthi, V. S.

    2014-01-01

    Cochlea devices are powered up with the help of batteries and they should possess long working life to avoid replacing of devices at regular interval of years. Hence the devices with low power consumptions are required. In cochlea devices there are numerous filters, each responsible for frequency variant signals, which helps in identifying speech signals of different audible range. In this paper, multiplierless lookup table (LUT) based auditory filter is implemented. Power aware adder architectures are utilized to add the output samples of the LUT, available at every clock cycle. The design is developed and modeled using Verilog HDL, simulated using Mentor Graphics Model-Sim Simulator, and synthesized using Synopsys Design Compiler tool. The design was mapped to TSMC 65 nm technological node. The standard ASIC design methodology has been adapted to carry out the power analysis. The proposed FIR filter architecture has reduced the leakage power by 15% and increased its performance by 2.76%. PMID:25506073

  19. Notch1 endocytosis is induced by ligand and is required for signal transduction.

    PubMed

    Chapman, G; Major, J A; Iyer, K; James, A C; Pursglove, S E; Moreau, J L M; Dunwoodie, S L

    2016-01-01

    The Notch signalling pathway is widely utilised during embryogenesis in situations where cell-cell interactions are important for cell fate specification and differentiation. DSL ligand endocytosis into the ligand-expressing cell is an important aspect of Notch signalling because it is thought to supply the force needed to separate the Notch heterodimer to initiate signal transduction. A functional role for receptor endocytosis during Notch signal transduction is more controversial. Here we have used live-cell imaging to examine trafficking of the Notch1 receptor in response to ligand binding. Contact with cells expressing ligands induced internalisation and intracellular trafficking of Notch1. Notch1 endocytosis was accompanied by transendocytosis of ligand into the Notch1-expressing signal-receiving cell. Ligand caused Notch1 endocytosis into SARA-positive endosomes in a manner dependent on clathrin and dynamin function. Moreover, inhibition of endocytosis in the receptor-expressing cell impaired ligand-induced Notch1 signalling. Our findings resolve conflicting observations from mammalian and Drosophila studies by demonstrating that ligand-dependent activation of Notch1 signalling requires receptor endocytosis. Endocytosis of Notch1 may provide a force on the ligand:receptor complex that is important for potent signal transduction. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. FGF signaling is required for brain left-right asymmetry and brain midline formation.

    PubMed

    Neugebauer, Judith M; Yost, H Joseph

    2014-02-01

    Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure.

  1. Murine Polyomavirus Cell Surface Receptors Activate Distinct Signaling Pathways Required for Infection

    PubMed Central

    O’Hara, Samantha D.

    2016-01-01

    ABSTRACT Virus binding to the cell surface triggers an array of host responses, including activation of specific signaling pathways that facilitate steps in virus entry. Using mouse polyomavirus (MuPyV), we identified host signaling pathways activated upon virus binding to mouse embryonic fibroblasts (MEFs). Pathways activated by MuPyV included the phosphatidylinositol 3-kinase (PI3K), FAK/SRC, and mitogen-activated protein kinase (MAPK) pathways. Gangliosides and α4-integrin are required receptors for MuPyV infection. MuPyV binding to both gangliosides and the α4-integrin receptors was required for activation of the PI3K pathway; however, either receptor interaction alone was sufficient for activation of the MAPK pathway. Using small-molecule inhibitors, we confirmed that the PI3K and FAK/SRC pathways were required for MuPyV infection, while the MAPK pathway was dispensable. Mechanistically, the PI3K pathway was required for MuPyV endocytosis, while the FAK/SRC pathway enabled trafficking of MuPyV along microtubules. Thus, MuPyV interactions with specific cell surface receptors facilitate activation of signaling pathways required for virus entry and trafficking. Understanding how different viruses manipulate cell signaling pathways through interactions with host receptors could lead to the identification of new therapeutic targets for viral infection. PMID:27803182

  2. Spacecraft-spacecraft radio-metric tracking: Signal acquisition requirements and application to Mars approach navigation

    NASA Technical Reports Server (NTRS)

    Kahn, R. D.; Thurman, S.; Edwards, C.

    1994-01-01

    Doppler and ranging measurements between spacecraft can be obtained only when the ratio of the total received signal power to noise power density (P(sub t)/N(sub 0)) at the receiving spacecraft is sufficiently large that reliable signal detection can be achieved within a reasonable time period. In this article, the requirement on P(sub t)/N(sub 0) for reliable carrier signal detection is calculated as a function of various system parameters, including characteristics of the spacecraft computing hardware and a priori uncertainty in spacecraft-spacecraft relative velocity and acceleration. Also calculated is the P(sub t)/N(sub 0) requirements for reliable detection of a ranging signal, consisting of a carrier with pseudonoise (PN) phase modulation. Once the P(sub t)/N(sub 0) requirement is determined, then for a given set of assumed spacecraft telecommunication characteristics (transmitted signal power, antenna gains, and receiver noise temperatures) it is possible to calculate the maximum range at which a carrier signal or ranging signal may be acquired. For example, if a Mars lander and a spacecraft approaching Mars are each equipped with 1-m-diameter antennas, the transmitted power is 5 W, and the receiver noise temperatures are 350 K, then S-band carrier signal acquisition can be achieved at ranges exceeding 10 million km. An error covariance analysis illustrates the utility of in situ Doppler and ranging measurements for Mars approach navigation. Covariance analysis results indicate that navigation accuracies of a few km can be achieved with either data type. The analysis also illustrates dependency of the achievable accuracy on the approach trajectory velocity.

  3. Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development

    PubMed Central

    Basson, M. Albert; Echevarria, Diego; Ahn, Christina Petersen; Sudarov, Anamaria; Joyner, Alexandra L.; Mason, Ivor J.; Martinez, Salvador; Martin, Gail R.

    2008-01-01

    SUMMARY Development of the prospective midbrain and cerebellum are coordinated by FGF ligands produced by the isthmic organizer. Previous studies have suggested that the midbrain and cerebellum require different levels of FGF signaling for their development. However, little is known about the extent to which specific regions within these two parts of the brain differ in their requirement for FGF signaling during embryogenesis. In this study, we have explored the effects of inhibiting FGF signaling within the embryonic midbrain (mesencephalon) and cerebellum (rhombomere 1) by misexpressing Sprouty2 (Spry2) specifically in the mouse mesencephalon and rhombomere 1 from an early stage. We show that such Spry2 misexpression moderately reduces FGF signaling, and that this reduction causes the death of cells in the anterior mesencephalon, the region furthest from the source of FGF ligands. Interestingly, the remaining cells in the posterior mesencephalon develop into anterior midbrain, indicating that a low level of FGF signaling is sufficient to promote only anterior midbrain development. Spry2 misexpression also affects development of the vermis, the medial part of the cerebellum that spans the midline. We found that whereas misexpression of Spry2 alone caused loss of the anterior vermis, reducing FGF signaling further, by decreasing Fgf8 gene dosage, resulted in loss of the entire vermis. We provide evidence that cell death is not responsible for this tissue loss. Instead, our data suggest that the vermis fails to develop because reducing FGF signaling perturbs the balance between vermis and roof plate development in rhombomere 1. We suggest a molecular explanation for this phenomenon by providing evidence that FGF signaling functions to inhibit the BMP signaling that promotes roof plate development. PMID:18216176

  4. How Does Auditory Training Work? Joined-Up Thinking and Listening.

    PubMed

    Ferguson, Melanie; Henshaw, Helen

    2015-11-01

    Auditory training aims to compensate for degradation in the auditory signal and is offered as an intervention to help alleviate the most common complaint in people with hearing loss, understanding speech in a background noise. Yet there remain many unanswered questions. This article reviews some of the key pieces of evidence that assess the evidence for whether, and how, auditory training benefits adults with hearing loss. The evidence supports that improvements occur on the trained task; however, transfer of that learning to generalized real-world benefit is much less robust. For more than a decade, there has been an increasing awareness of the role that cognition plays in listening. But more recently in the auditory training literature, there has been an increased focus on assessing how cognitive performance relevant for listening may improve with training. We argue that this is specifically the case for measures that index executive processes, such as monitoring, attention switching, and updating of working memory, all of which are required for successful listening and communication in challenging or adverse listening conditions. We propose combined auditory-cognitive training approaches, where training interventions develop cognition embedded within auditory tasks, which are most likely to offer generalized benefits to the real-world listening abilities of people with hearing loss.

  5. Auditory processing efficiency deficits in children with developmental language impairments

    NASA Astrophysics Data System (ADS)

    Hartley, Douglas E. H.; Moore, David R.

    2002-12-01

    The ``temporal processing hypothesis'' suggests that individuals with specific language impairments (SLIs) and dyslexia have severe deficits in processing rapidly presented or brief sensory information, both within the auditory and visual domains. This hypothesis has been supported through evidence that language-impaired individuals have excess auditory backward masking. This paper presents an analysis of masking results from several studies in terms of a model of temporal resolution. Results from this modeling suggest that the masking results can be better explained by an ``auditory efficiency'' hypothesis. If impaired or immature listeners have a normal temporal window, but require a higher signal-to-noise level (poor processing efficiency), this hypothesis predicts the observed small deficits in the simultaneous masking task, and the much larger deficits in backward and forward masking tasks amongst those listeners. The difference in performance on these masking tasks is predictable from the compressive nonlinearity of the basilar membrane. The model also correctly predicts that backward masking (i) is more prone to training effects, (ii) has greater inter- and intrasubject variability, and (iii) increases less with masker level than do other masking tasks. These findings provide a new perspective on the mechanisms underlying communication disorders and auditory masking.

  6. Central auditory function of deafness genes.

    PubMed

    Willaredt, Marc A; Ebbers, Lena; Nothwang, Hans Gerd

    2014-06-01

    The highly variable benefit of hearing devices is a serious challenge in auditory rehabilitation. Various factors contribute to this phenomenon such as the diversity in ear defects, the different extent of auditory nerve hypoplasia, the age of intervention, and cognitive abilities. Recent analyses indicate that, in addition, central auditory functions of deafness genes have to be considered in this context. Since reduced neuronal activity acts as the common denominator in deafness, it is widely assumed that peripheral deafness influences development and function of the central auditory system in a stereotypical manner. However, functional characterization of transgenic mice with mutated deafness genes demonstrated gene-specific abnormalities in the central auditory system as well. A frequent function of deafness genes in the central auditory system is supported by a genome-wide expression study that revealed significant enrichment of these genes in the transcriptome of the auditory brainstem compared to the entire brain. Here, we will summarize current knowledge of the diverse central auditory functions of deafness genes. We furthermore propose the intimately interwoven gene regulatory networks governing development of the otic placode and the hindbrain as a mechanistic explanation for the widespread expression of these genes beyond the cochlea. We conclude that better knowledge of central auditory dysfunction caused by genetic alterations in deafness genes is required. In combination with improved genetic diagnostics becoming currently available through novel sequencing technologies, this information will likely contribute to better outcome prediction of hearing devices.

  7. Calcium signaling and the MAPK cascade are required for sperm activation in Caenorhabditis elegans.

    PubMed

    Liu, Zhiyu; Wang, Bin; He, Ruijun; Zhao, Yanmei; Miao, Long

    2014-02-01

    In nematode, sperm activation (or spermiogenesis), a process in which the symmetric and non-motile spermatids transform into polarized and crawling spermatozoa, is critical for sperm cells to acquire fertilizing competence. SPE-8 dependent and SPE-8 independent pathways function redundantly during sperm activation in both males and hermaphrodites of Caenorhabditis elegans. However, the downstream signaling for both pathways remains unclear. Here we show that calcium signaling and the MAPK cascade are required for both SPE-8 dependent and SPE-8 independent sperm activation, implying that both pathways share common downstream signaling components during sperm activation. We demonstrate that activation of the MAPK cascade is sufficient to activate spermatids derived from either wild-type or spe-8 group mutant males and that activation of the MAPK cascade bypasses the requirement of calcium signal to induce sperm activation, indicating that the MAPK cascade functions downstream of or parallel with the calcium signaling during sperm activation. Interestingly, the persistent activation of MAPK in activated spermatozoa inhibits Major Sperm Protein (MSP)-based cytoskeleton dynamics. We demonstrate that MAPK plays dual roles in promoting pseudopod extension during sperm activation but also blocking the MSP-based, amoeboid motility of the spermatozoa. Thus, though nematode sperm are crawling cells, morphologically distinct from flagellated sperm, and the molecular machinery for motility of amoeboid and flagellated sperm is different, both types of sperm might utilize conserved signaling pathways to modulate sperm maturation.

  8. Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition.

    PubMed

    Fumoto, Katsumi; Takigawa-Imamura, Hisako; Sumiyama, Kenta; Kaneiwa, Tomoyuki; Kikuchi, Akira

    2017-01-01

    In lung development, the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage. Subsequently, these epithelial cells change shape into the flat or cuboidal pneumocytes that form the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shape on tissue morphogenesis remains unclear. Here, we show that the expression of Wnt components is decreased in the canalicular-saccular stages, and that genetically constitutive activation of Wnt signaling impairs air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrate that Wnt signaling induces apical constriction through apical actomyosin cytoskeletal organization. Mathematical modeling reveals that apical constriction induces bud formation and that loss of apical constriction is required for the formation of an air sac-like structure. We identify MAP/microtubule affinity-regulating kinase 1 (Mark1) as a downstream molecule of Wnt signaling and show that it is required for apical cytoskeletal organization and bud formation. These results suggest that Wnt signaling is required for bud formation by inducing apical constriction during the pseudoglandular stage, whereas loss of Wnt signaling is necessary for air sac formation in the canalicular-saccular stages. © 2017. Published by The Company of Biologists Ltd.

  9. Managing Quality in Higher Education Systems via Minimal Quality Requirements: Signaling and Control.

    ERIC Educational Resources Information Center

    Mizrahi, Shlomo; Mehrez, Abraham

    2002-01-01

    Discusses two versions of a signaling game to set minimal quality requirements for higher education applicants in Israel: one assumes low sensitivity to quality, the other high sensitivity. Concludes that indirect government influence on quality variations in applicant pool is more effective in controlling institutional quality then direct…

  10. Induction and prepatterning of the zebrafish pectoral fin bud requires axial retinoic acid signaling.

    PubMed

    Gibert, Yann; Gajewski, Alexandra; Meyer, Axel; Begemann, Gerrit

    2006-07-01

    Vertebrate forelimbs arise as bilateral appendages from the lateral plate mesoderm (LPM). Mutants in aldh1a2 (raldh2), an embryonically expressed gene encoding a retinoic acid (RA)-synthesizing enzyme, have been used to show that limb development and patterning of the limb bud are crucially dependent on RA signaling. However, the timing and cellular origin of RA signaling in these processes have remained poorly resolved. We have used genetics and chemical modulators of RA signaling to resolve these issues in the zebrafish. By rescuing pectoral fin induction in the aldh1a2/neckless mutant with exogenous RA and by blocking RA signaling in wild-type embryos, we find that RA acts as a permissive signal that is required during the six- to eight-somite stages for pectoral fin induction. Cell-transplantation experiments show that RA production is not only crucially required from flanking somites, but is sufficient to permit fin bud initiation when the trunk mesoderm is genetically ablated. Under the latter condition, intermediate mesoderm alone cannot induce the pectoral fin field in the LPM. We further show that induction of the fin field is directly followed by a continued requirement for somite-derived RA signaling to establish a prepattern of anteroposterior fates in the condensing fin mesenchyme. This process is mediated by the maintained expression of the transcription factor hand2, through which the fin field is continuously posteriorized, and lasts up to several hours prior to limb-budding. Thus, RA signaling from flanking somites plays a dual early role in the condensing limb bud mesenchyme.

  11. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    PubMed

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells.

  12. Notch-signalling is required for head regeneration and tentacle patterning in Hydra.

    PubMed

    Münder, Sandra; Tischer, Susanne; Grundhuber, Maresa; Büchels, Nathalie; Bruckmeier, Nadine; Eckert, Stefanie; Seefeldt, Carolin A; Prexl, Andrea; Käsbauer, Tina; Böttger, Angelika

    2013-11-01

    Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated. The molecular components of this organising region involve Wnt-signalling and β-catenin. However, it is not known how correct patterning of hypostome and tentacles are achieved in the hydra head and whether other signals in addition to HyWnt3 are needed for re-establishing the new organiser after head removal. Here we show that Notch-signalling is required for re-establishing the organiser during regeneration and that this is due to its role in restricting tentacle activation. Blocking Notch-signalling leads to the formation of irregular head structures characterised by excess tentacle tissue and aberrant expression of genes that mark the tentacle boundaries. This indicates a role for Notch-signalling in defining the tentacle pattern in the hydra head. Moreover, lateral inhibition by HvNotch and its target HyHes are required for head regeneration and without this the formation of the β-catenin/Wnt dependent head organiser is impaired. Work on prebilaterian model organisms has shown that the Wnt-pathway is important for setting up signalling centres for axial patterning in early multicellular animals. Our data suggest that the integration of Wnt-signalling with Notch-Delta activity was also involved in the evolution of defined body plans in animals. © 2013 Elsevier Inc. All rights reserved.

  13. ABC Transporter Required for Intercellular Transfer of Developmental Signals in a Heterocystous Cyanobacterium

    PubMed Central

    Videau, Patrick; Rivers, Orion S.; Higa, Kelly C.

    2015-01-01

    ABSTRACT In the filamentous cyanobacterium Anabaena, patS and hetN encode peptide-derived signals with many of the properties of morphogens. These signals regulate the formation of a periodic pattern of heterocysts by lateral inhibition of differentiation. Here we show that intercellular transfer of the patS- and hetN-dependent developmental signals from heterocysts to vegetative cells requires HetC, a predicted ATP-binding cassette transporter (ABC transporter). Relative to the wild type, in a hetC mutant differentiation resulted in a reduced number of heterocysts that were incapable of nitrogen fixation, but deletion of patS or hetN restored heterocyst number and function in a hetC background. These epistasis results suggest that HetC is necessary for conferring self-immunity to the inhibitors on differentiating cells. Nine hours after induction of differentiation, HetC was required for neither induction of transcription of patS nor intercellular transfer of the patS-encoded signal to neighboring cells. Conversely, in strains lacking HetC, the patS- and hetN-encoded signals were not transferred from heterocyst cells to adjacent vegetative cells. The results support a model in which the patS-dependent signal is initially transferred between vegetative cells in a HetC-independent fashion, but some time before morphological differentiation of heterocysts is complete, transfer of both signals transitions to a HetC-dependent process. IMPORTANCE How chemical cues that regulate pattern formation in multicellular organisms move from one cell to another is a central question in developmental biology. In this study, we show that an ABC transporter, HetC, is necessary for transport of two developmental signals between different types of cells in a filamentous cyanobacterium. ABC transporters are found in organisms as diverse as bacteria and humans and, as the name implies, are often involved in the transport of molecules across a cellular membrane. The activity of HetC was

  14. SNMP is a signaling component required for pheromone sensitivity in Drosophila.

    PubMed

    Jin, Xin; Ha, Tal Soo; Smith, Dean P

    2008-08-05

    The only known volatile pheromone in Drosophila, 11-cis-vaccenyl acetate (cVA), mediates a variety of behaviors including aggregation, mate recognition, and sexual behavior. cVA is detected by a small set of olfactory neurons located in T1 trichoid sensilla on the antennae of males and females. Two components known to be required for cVA reception are the odorant receptor Or67d and the extracellular pheromone-binding protein LUSH. Using a genetic screen for cVA-insensitive mutants, we have identified a third component required for cVA reception: sensory neuron membrane protein (SNMP). SNMP is a homolog of CD36, a scavenger receptor important for lipoprotein binding and uptake of cholesterol and lipids in vertebrates. In humans, loss of CD36 is linked to a wide range of disorders including insulin resistance, dyslipidemia, and atherosclerosis, but how CD36 functions in lipid transport and signal transduction is poorly understood. We show that SNMP is required in pheromone-sensitive neurons for cVA sensitivity but is not required for sensitivity to general odorants. Using antiserum to SNMP infused directly into the sensillum lymph, we show that SNMP function is required on the dendrites of cVA-sensitive neurons; this finding is consistent with a direct role in cVA signal transduction. Therefore, pheromone perception in Drosophila should serve as an excellent model to elucidate the role of CD36 members in transmembrane signaling.

  15. Hippocampal long-term depression is facilitated by the acquisition and updating of memory of spatial auditory content and requires mGlu5 activation.

    PubMed

    Dietz, Birte; Manahan-Vaughan, Denise

    2017-03-15

    Long-term potentiation (LTP) and long-term depression (LTD) are key cellular processes that support memory formation. Whereas increases of synaptic strength by means of LTP may support the creation of a spatial memory 'engram', LTD appears to play an important role in refining and optimising experience-dependent encoding. A differentiation in the role of hippocampal subfields is apparent. For example, LTD in the dentate gyrus (DG) is enabled by novel learning about large visuospatial features, whereas in area CA1, it is enabled by learning about discrete aspects of spatial content, whereby, both discrete visuospatial and olfactospatial cues trigger LTD in CA1. Here, we explored to what extent local audiospatial cues facilitate information encoding in the form of LTD in these subfields. Coupling of low frequency afferent stimulation (LFS) with discretely localised, novel auditory tones in the sonic hearing, or ultrasonic range, facilitated short-term depression (STD) into LTD (>24 h) in CA1, but not DG. Re-exposure to the now familiar audiospatial configuration ca. 1 week later failed to enhance STD. Reconfiguration of the same audiospatial cues resulted anew in LTD when ultrasound, but not non-ultrasound cues were used. LTD facilitation that was triggered by novel exposure to spatially arranged tones, or to spatial reconfiguration of the same tones were both prevented by an antagonism of the metabotropic glutamate receptor, mGlu5. These data indicate that, if behaviourally salient enough, the hippocampus can use audiospatial cues to facilitate LTD that contributes to the encoding and updating of spatial representations. Effects are subfield-specific, and require mGlu5 activation, as is the case for visuospatial information processing. These data reinforce the likelihood that LTD supports the encoding of spatial features, and that this occurs in a qualitative and subfield-specific manner. They also support that mGlu5 is essential for synaptic encoding of spatial

  16. Auditory imagery and the poor-pitch singer.

    PubMed

    Pfordresher, Peter Q; Halpern, Andrea R

    2013-08-01

    The vocal imitation of pitch by singing requires one to plan laryngeal movements on the basis of anticipated target pitch events. This process may rely on auditory imagery, which has been shown to activate motor planning areas. As such, we hypothesized that poor-pitch singing, although not typically associated with deficient pitch perception, may be associated with deficient auditory imagery. Participants vocally imitated simple pitch sequences by singing, discriminated pitch pairs on the basis of pitch height, and completed an auditory imagery self-report questionnaire (the Bucknell Auditory Imagery Scale). The percentage of trials participants sung in tune correlated significantly with self-reports of vividness for auditory imagery, although not with the ability to control auditory imagery. Pitch discrimination was not predicted by auditory imagery scores. The results thus support a link between auditory imagery and vocal imitation.

  17. Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex

    PubMed Central

    Xing, Lei; Larsen, Rylan S; Bjorklund, George Reed; Li, Xiaoyan; Wu, Yaohong; Philpot, Benjamin D; Snider, William D; Newbern, Jason M

    2016-01-01

    Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2+ neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability. DOI: http://dx.doi.org/10.7554/eLife.11123.001 PMID:26848828

  18. Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa.

    PubMed

    Walsh, Catherine; Gangloff, Monique; Monie, Tom; Smyth, Tomoko; Wei, Bin; McKinley, Trevelyan J; Maskell, Duncan; Gay, Nicholas; Bryant, Clare

    2008-07-15

    LPS signals through a membrane bound-complex of the lipid binding protein MD-2 and the receptor TLR4. In this study we identify discrete regions in both MD-2 and TLR4 that are required for signaling by lipid IVa, an LPS derivative that is an agonist in horse but an antagonist in humans. We show that changes in the electrostatic surface potential of both MD-2 and TLR4 are required in order that lipid IVa can induce signaling. In MD-2, replacing horse residues 57-66 and 82-89 with the equivalent human residues confers a level of constitutive activity on horse MD-2, suggesting that conformational switching in this protein is likely to be important in ligand-induced activation of MD-2/TLR4. We identify leucine-rich repeat 14 in the C terminus of TLR4 as essential for lipid IVa activation of MD-2/TLR4. Remarkably, we identify a single residue in the glycan-free flank of the horse TLR4 solenoid that confers the ability to signal in response to lipid IVa. These results suggest a mechanism of signaling that involves crosslinking mediated by both MD-2-receptor and receptor-receptor contacts in a model that shows striking similarities to the recently published structure (Cell 130: 1071-1082) of the ligand-bound TLR1/2 ectodomain heterodimer.

  19. Cooperativity between MAPK and PI3K signaling activation is required for glioblastoma pathogenesis

    PubMed Central

    Vitucci, Mark; Karpinich, Natalie O.; Bash, Ryan E.; Werneke, Andrea M.; Schmid, Ralf S.; White, Kristen K.; McNeill, Robert S.; Huff, Byron; Wang, Sophie; Van Dyke, Terry; Miller, C. Ryan

    2013-01-01

    Background Glioblastoma (GBM) genomes feature recurrent genetic alterations that dysregulate core intracellular signaling pathways, including the G1/S cell cycle checkpoint and the MAPK and PI3K effector arms of receptor tyrosine kinase (RTK) signaling. Elucidation of the phenotypic consequences of activated RTK effectors is required for the design of effective therapeutic and diagnostic strategies. Methods Genetically defined, G1/S checkpoint-defective cortical murine astrocytes with constitutively active Kras and/or Pten deletion mutations were used to systematically investigate the individual and combined roles of these 2 RTK signaling effectors in phenotypic hallmarks of glioblastoma pathogenesis, including growth, migration, and invasion in vitro. A novel syngeneic orthotopic allograft model system was used to examine in vivo tumorigenesis. Results Constitutively active Kras and/or Pten deletion mutations activated both MAPK and PI3K signaling. Their combination led to maximal growth, migration, and invasion of G1/S-defective astrocytes in vitro and produced progenitor-like transcriptomal profiles that mimic human proneural GBM. Activation of both RTK effector arms was required for in vivo tumorigenesis and produced highly invasive, proneural-like GBM. Conclusions These results suggest that cortical astrocytes can be transformed into GBM and that combined dysregulation of MAPK and PI3K signaling revert G1/S-defective astrocytes to a primitive gene expression state. This genetically-defined, immunocompetent model of proneural GBM will be useful for preclinical development of MAPK/PI3K-targeted, subtype-specific therapies. PMID:23814263

  20. Ageing and the auditory system

    PubMed Central

    Howarth, A; Shone, G R

    2006-01-01

    There are a number of pathophysiological processes underlying age related changes in the auditory system. The effects of hearing loss can have consequences beyond the immediate loss of hearing, and may have profound effects on the functioning of the person. While a deficit in hearing can be corrected to some degree by a hearing aid, auditory rehabilitation requires much more than simply amplifying external sound. It is important that those dealing with elderly people are aware of all the issues involved in age related hearing loss. PMID:16517797

  1. Genetic Requirements for Signaling from an Autoactive Plant NB-LRR Intracellular Innate Immune Receptor

    PubMed Central

    Stallmann, Anna; Dangl, Jeffery L.; Bonardi, Vera

    2013-01-01

    Plants react to pathogen attack via recognition of, and response to, pathogen-specific molecules at the cell surface and inside the cell. Pathogen effectors (virulence factors) are monitored by intracellular nucleotide-binding leucine-rich repeat (NB-LRR) sensor proteins in plants and mammals. Here, we study the genetic requirements for defense responses of an autoactive mutant of ADR1-L2, an Arabidopsis coiled-coil (CC)-NB-LRR protein. ADR1-L2 functions upstream of salicylic acid (SA) accumulation in several defense contexts, and it can act in this context as a “helper” to transduce specific microbial activation signals from “sensor” NB-LRRs. This helper activity does not require an intact P-loop. ADR1-L2 and another of two closely related members of this small NB-LRR family are also required for propagation of unregulated runaway cell death (rcd) in an lsd1 mutant. We demonstrate here that, in this particular context, ADR1-L2 function is P-loop dependent. We generated an autoactive missense mutation, ADR1-L2D484V, in a small homology motif termed MHD. Expression of ADR1-L2D848V leads to dwarfed plants that exhibit increased disease resistance and constitutively high SA levels. The morphological phenotype also requires an intact P-loop, suggesting that these ADR1-L2D484V phenotypes reflect canonical activation of this NB-LRR protein. We used ADR1-L2D484V to define genetic requirements for signaling. Signaling from ADR1-L2D484V does not require NADPH oxidase and is negatively regulated by EDS1 and AtMC1. Transcriptional regulation of ADR1-L2D484V is correlated with its phenotypic outputs; these outputs are both SA–dependent and –independent. The genetic requirements for ADR1-L2D484V activity resemble those that regulate an SA–gradient-dependent signal amplification of defense and cell death signaling initially observed in the absence of LSD1. Importantly, ADR1-L2D484V autoactivation signaling is controlled by both EDS1 and SA in separable, but linked

  2. Presenilin-mediated transmembrane cleavage is required for Notch signal transduction in Drosophila

    PubMed Central

    Struhl, Gary; Greenwald, Iva

    2001-01-01

    The cleavage model for signal transduction by receptors of the LIN-12/Notch family posits that ligand binding leads to cleavage within the transmembrane domain, so that the intracellular domain is released to translocate to the nucleus and activate target gene expression. The familial Alzheimer's disease-associated protein Presenilin is required for LIN-12/Notch signaling, and several lines of evidence suggest that Presenilin mediates the transmembrane cleavage event that releases the LIN-12/Notch intracellular domain. However, doubt was cast on this possibility by a report that Presenilin is not required for the transducing activity of NECN, a constitutively active transmembrane form of Notch, in Drosophila. Here, we have reassessed this finding and show instead that Presenilin is required for activity of NECN for all cell fate decisions examined. Our results indicate that transmembrane cleavage and signal transduction are strictly correlated, supporting the cleavage model for signal transduction by LIN-12/Notch and a role for Presenilin in mediating the ligand-induced transmembrane cleavage. PMID:11134525

  3. Auditory Neuropathy

    MedlinePlus

    ... hair cells? Outer hair cells help amplify sound vibrations entering the inner ear from the middle ear. ... working normally, the inner hair cells convert these vibrations into electrical signals that travel as nerve impulses ...

  4. Demodulation processes in auditory perception

    NASA Astrophysics Data System (ADS)

    Feth, Lawrence L.

    1994-08-01

    The long range goal of this project is the understanding of human auditory processing of information conveyed by complex, time-varying signals such as speech, music or important environmental sounds. Our work is guided by the assumption that human auditory communication is a 'modulation - demodulation' process. That is, we assume that sound sources produce a complex stream of sound pressure waves with information encoded as variations ( modulations) of the signal amplitude and frequency. The listeners task then is one of demodulation. Much of past. psychoacoustics work has been based in what we characterize as 'spectrum picture processing.' Complex sounds are Fourier analyzed to produce an amplitude-by-frequency 'picture' and the perception process is modeled as if the listener were analyzing the spectral picture. This approach leads to studies such as 'profile analysis' and the power-spectrum model of masking. Our approach leads us to investigate time-varying, complex sounds. We refer to them as dynamic signals and we have developed auditory signal processing models to help guide our experimental work.

  5. Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development

    PubMed Central

    Skouloudaki, Kassiani; Puetz, Michael; Simons, Matias; Courbard, Jean-Remy; Boehlke, Christopher; Hartleben, Björn; Engel, Christina; Moeller, Marcus J.; Englert, Christoph; Bollig, Frank; Schäfer, Tobias; Ramachandran, Haribaskar; Mlodzik, Marek; Huber, Tobias B.; Kuehn, E. Wolfgang; Kim, Emily; Kramer-Zucker, Albrecht; Walz, Gerd

    2009-01-01

    Spatial organization of cells and their appendages is controlled by the planar cell polarity pathway, a signaling cascade initiated by the protocadherin Fat in Drosophila. Vertebrates express 4 Fat molecules, Fat1–4. We found that depletion of Fat1 caused cyst formation in the zebrafish pronephros. Knockdown of the PDZ domain containing the adaptor protein Scribble intensified the cyst-promoting phenotype of Fat1 depletion, suggesting that Fat1 and Scribble act in overlapping signaling cascades during zebrafish pronephros development. Supporting the genetic interaction with Fat1, Scribble recognized the PDZ-binding site of Fat1. Depletion of Yes-associated protein 1 (YAP1), a transcriptional co-activator inhibited by Hippo signaling, ameliorated the cyst formation in Fat1-deficient zebrafish, whereas Scribble inhibited the YAP1-induced cyst formation. Thus, reduced Hippo signaling and subsequent YAP1 disinhibition seem to play a role in the development of pronephric cysts after depletion of Fat1 or Scribble. We hypothesize that Hippo signaling is required for normal pronephros development in zebrafish and that Scribble is a candidate link between Fat and the Hippo signaling cascade in vertebrates. PMID:19439659

  6. Intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory.

    PubMed

    Takeda, Atsushi; Tamano, Haruna; Ogawa, Taisuke; Takada, Shunsuke; Nakamura, Masatoshi; Fujii, Hiroaki; Ando, Masaki

    2014-11-01

    The role of perforant pathway-dentate granule cell synapses in cognitive behavior was examined focusing on synaptic Zn(2+) signaling in the dentate gyrus. Object recognition memory was transiently impaired when extracellular Zn(2+) levels were decreased by injection of clioquinol and N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylendediamine. To pursue the effect of the loss and/or blockade of Zn(2+) signaling in dentate granule cells, ZnAF-2DA (100 pmol, 0.1 mM/1 µl), an intracellular Zn(2+) chelator, was locally injected into the dentate molecular layer of rats. ZnAF-2DA injection, which was estimated to chelate intracellular Zn(2+) signaling only in the dentate gyrus, affected object recognition memory 1 h after training without affecting intracellular Ca(2+) signaling in the dentate molecular layer. In vivo dentate gyrus long-term potentiation (LTP) was affected under the local perfusion of the recording region (the dentate granule cell layer) with 0.1 mM ZnAF-2DA, but not with 1-10 mM CaEDTA, an extracellular Zn(2+) chelator, suggesting that the blockade of intracellular Zn(2+) signaling in dentate granule cells affects dentate gyrus LTP. The present study demonstrates that intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory, probably via dentate gyrus LTP expression.

  7. Perception of stochastically undersampled sound waveforms: a model of auditory deafferentation

    PubMed Central

    Lopez-Poveda, Enrique A.; Barrios, Pablo

    2013-01-01

    Auditory deafferentation, or permanent loss of auditory nerve afferent terminals, occurs after noise overexposure and aging and may accompany many forms of hearing loss. It could cause significant auditory impairment but is undetected by regular clinical tests and so its effects on perception are poorly understood. Here, we hypothesize and test a neural mechanism by which deafferentation could deteriorate perception. The basic idea is that the spike train produced by each auditory afferent resembles a stochastically digitized version of the sound waveform and that the quality of the waveform representation in the whole nerve depends on the number of aggregated spike trains or auditory afferents. We reason that because spikes occur stochastically in time with a higher probability for high- than for low-intensity sounds, more afferents would be required for the nerve to faithfully encode high-frequency or low-intensity waveform features than low-frequency or high-intensity features. Deafferentation would thus degrade the encoding of these features. We further reason that due to the stochastic nature of nerve firing, the degradation would be greater in noise than in quiet. This hypothesis is tested using a vocoder. Sounds were filtered through ten adjacent frequency bands. For the signal in each band, multiple stochastically subsampled copies were obtained to roughly mimic different stochastic representations of that signal conveyed by different auditory afferents innervating a given cochlear region. These copies were then aggregated to obtain an acoustic stimulus. Tone detection and speech identification tests were performed by young, normal-hearing listeners using different numbers of stochastic samplers per frequency band in the vocoder. Results support the hypothesis that stochastic undersampling of the sound waveform, inspired by deafferentation, impairs speech perception in noise more than in quiet, consistent with auditory aging effects. PMID:23882176

  8. Dicer is Required for the Maintenance of Notch Signaling and Gliogenic Competence During Mouse Retinal Development

    PubMed Central

    Georgi, Sean A.; Reh, Thomas A.

    2017-01-01

    MicroRNAs (miRNAs) are 19–25 nucleotide RNAs that regulate messenger RNA translation and stability. Recently, we performed a conditional knockout (CKO) of the miRNA-processing enzyme Dicer during mouse retinal development and showed an essential role for miRNAs in the transition of retinal progenitors from an early to a late competence state (Georgi and Reh [2010]: J Neurosci 30:4048–4061). Notably, Dicer CKO progenitors failed to express Ascl1 and generated ganglion cells beyond their normal competence window. Because Ascl1 regulates multiple Notch signaling components, we hypothesized that Notch signaling is downregulated in Dicer CKO retinas. We show here that Notch signaling is severely reduced in Dicer CKO retinas, but that retinal progenitors still retain a low level of Notch signaling. By increasing Notch signaling in Dicer CKO progenitors through constitutive expression of the Notch intra-cellular domain (NICD), we show that transgenic rescue of Notch signaling has little effect on the competence of retinal progenitors or the enhanced generation of ganglion cells, suggesting that loss of Notch signaling is not a major determinant of these phenotypes. Nevertheless, transgenic NICD expression restored horizontal cells, suggesting an interaction between miRNAs and Notch signaling in the development of this cell type. Furthermore, while NICD overexpression leads to robust glial induction in control retinas, NICD overexpression was insufficient to drive Dicer-null retinal progenitors to a glial fate. Surprisingly, the presence of transgenic NICD expression did not prevent the differentiation of some types of retinal neurons, suggesting that Notch inactivation is not an absolute requirement for the initial stages of neuronal differentiation. PMID:21542136

  9. Nodal signaling is required for closure of the anterior neural tube in zebrafish

    PubMed Central

    Aquilina-Beck, Allisan; Ilagan, Kristine; Liu, Qin; Liang, Jennifer O

    2007-01-01

    Background Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish. Results We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFβ Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish. Conclusion This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain. PMID:17996054

  10. Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling

    PubMed Central

    Hines, D J; Schmitt, L I; Hines, R M; Moss, S J; Haydon, P G

    2013-01-01

    Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions of sleep deprivation. Here, we found that astrocytic signaling to adenosine (A1) receptors was required for the robust reduction of depressive-like behaviors following 12 hours of sleep deprivation. As sleep deprivation activates synaptic A1 receptors, we mimicked the effect of sleep deprivation on depression phenotypes by administration of the A1 agonist CCPA. These results provide the first mechanistic insight into how sleep deprivation impacts mood, and provide a novel pathway for rapid antidepressant development by modulation of glial signaling in the brain. PMID:23321809

  11. Neural mechanisms underlying auditory feedback control of speech.

    PubMed

    Tourville, Jason A; Reilly, Kevin J; Guenther, Frank H

    2008-02-01

    The neural substrates underlying auditory feedback control of speech were investigated using a combination of functional magnetic resonance imaging (fMRI) and computational modeling. Neural responses were measured while subjects spoke monosyllabic words under two conditions: (i) normal auditory feedback of their speech and (ii) auditory feedback in which the first formant frequency of their speech was unexpectedly shifted in real time. Acoustic measurements showed compensation to the shift within approximately 136 ms of onset. Neuroimaging revealed increased activity in bilateral superior temporal cortex during shifted feedback, indicative of neurons coding mismatches between expected and actual auditory signals, as well as right prefrontal and Rolandic cortical activity. Structural equation modeling revealed increased influence of bilateral auditory cortical areas on right frontal areas during shifted speech, indicating that projections from auditory error cells in posterior superior temporal cortex to motor correction cells in right frontal cortex mediate auditory feedback control of speech.

  12. In the newborn hippocampus, neurotrophin-dependent survival requires spontaneous activity and integrin signaling

    PubMed Central

    Murase, Sachiko; Owens, David F.; McKay, Ronald D.

    2012-01-01

    The nervous system develops through a program that first produces neurons in excess and then eliminates as many as half in a specific period of early post-natal life. Neurotrophins are widely thought to regulate neuronal survival but this role has not been clearly defined in the central nervous system. Here we show that neurotrophins promote survival of young neurons by promoting spontaneous activity. Survival of hippocampal neurons in neonatal rat requires spontaneous activity that depends on the excitatory action of γ-aminobutyric acid (GABA). Neurotrophins facilitate recruitment of cultured neurons into active networks, and it is this activity, combined with integrin receptor signaling, that controls neuronal survival. In vivo, neurotrophins require integrin signaling to control neuron number. These data are the first to link the early excitatory action of GABA to the developmental death period and to assign an essential role for activity in neurotrophin-mediated survival that establishes appropriate networks. PMID:21613492

  13. Vesicular Glutamate Transporter 1 Is Required for Photoreceptor Synaptic Signaling But Not For Intrinsic Visual Functions

    PubMed Central

    Johnson, Juliette; Fremeau, Robert T.; Duncan, Jacque L.; Rentería, René C.; Yang, Haidong; Hua, Zhaolin; Liu, Xiaorong; LaVail, Matthew M.; Edwards, Robert H.; Copenhagen, David R.

    2008-01-01

    Glutamatergic neurotransmission requires vesicular glutamate transporters (VGLUTs) to sequester glutamate into synaptic vesicles. Generally, VGLUT1 and VGLUT2 isoforms show complementary expression in the CNS and retina. However, little is known about whether isoform-specific expression serves distinct pathways and physiological functions. Here, by examining visual functions in VGLUT1-null mice, we demonstrate that visual signaling from photoreceptors to retinal output neurons requires VGLUT1. However, photoentrainment and pupillary light responses are preserved. We provide evidence that melanopsin-containing, intrinsically photosensitive retinal ganglion cells (RGCs), signaling via VGLUT2 pathways, support these non-image-forming functions. We conclude that VGLUT1 is essential for transmitting visual signals from photoreceptors to second- and third-order neurons, but VGLUT1 is not necessary for intrinsic visual functions. Furthermore, melanopsin and VGLUT2 expression in a subset of RGCs immediately after birth strongly supports the idea that intrinsic vision can function well before rod- and cone-mediated signaling has matured. PMID:17611277

  14. TGFβ/Activin signalling is required for ribosome biogenesis and cell growth in Drosophila salivary glands.

    PubMed

    Martins, Torcato; Eusebio, Nadia; Correia, Andreia; Marinho, Joana; Casares, Fernando; Pereira, Paulo S

    2017-01-01

    Signalling by TGFβ superfamily factors plays an important role in tissue growth and cell proliferation. In Drosophila, the activity of the TGFβ/Activin signalling branch has been linked to the regulation of cell growth and proliferation, but the cellular and molecular basis for these functions are not fully understood. In this study, we show that both the RII receptor Punt (Put) and the R-Smad Smad2 are strongly required for cell and tissue growth. Knocking down the expression of Put or Smad2 in salivary glands causes alterations in nucleolar structure and functions. Cells with decreased TGFβ/Activin signalling accumulate intermediate pre-rRNA transcripts containing internal transcribed spacer 1 regions accompanied by the nucleolar retention of ribosomal proteins. Thus, our results show that TGFβ/Activin signalling is required for ribosomal biogenesis, a key aspect of cellular growth control. Importantly, overexpression of Put enhanced cell growth induced by Drosophila Myc, a well-characterized inducer of nucleolar hypertrophy and ribosome biogenesis.

  15. TGFβ/Activin signalling is required for ribosome biogenesis and cell growth in Drosophila salivary glands

    PubMed Central

    Eusebio, Nadia; Correia, Andreia; Marinho, Joana; Casares, Fernando

    2017-01-01

    Signalling by TGFβ superfamily factors plays an important role in tissue growth and cell proliferation. In Drosophila, the activity of the TGFβ/Activin signalling branch has been linked to the regulation of cell growth and proliferation, but the cellular and molecular basis for these functions are not fully understood. In this study, we show that both the RII receptor Punt (Put) and the R-Smad Smad2 are strongly required for cell and tissue growth. Knocking down the expression of Put or Smad2 in salivary glands causes alterations in nucleolar structure and functions. Cells with decreased TGFβ/Activin signalling accumulate intermediate pre-rRNA transcripts containing internal transcribed spacer 1 regions accompanied by the nucleolar retention of ribosomal proteins. Thus, our results show that TGFβ/Activin signalling is required for ribosomal biogenesis, a key aspect of cellular growth control. Importantly, overexpression of Put enhanced cell growth induced by Drosophila Myc, a well-characterized inducer of nucleolar hypertrophy and ribosome biogenesis. PMID:28123053

  16. Auditory Imagery: Empirical Findings

    ERIC Educational Resources Information Center

    Hubbard, Timothy L.

    2010-01-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d)…

  17. Auditory Imagery: Empirical Findings

    ERIC Educational Resources Information Center

    Hubbard, Timothy L.

    2010-01-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d)…

  18. Passive auditory stimulation improves vision in hemianopia.

    PubMed

    Lewald, Jörg; Tegenthoff, Martin; Peters, Sören; Hausmann, Markus

    2012-01-01

    Techniques employed in rehabilitation of visual field disorders such as hemianopia are usually based on either visual or audio-visual stimulation and patients have to perform a training task. Here we present results from a completely different, novel approach that was based on passive unimodal auditory stimulation. Ten patients with either left or right-sided pure hemianopia (without neglect) received one hour of unilateral passive auditory stimulation on either their anopic or their intact side by application of repetitive trains of sound pulses emitted simultaneously via two loudspeakers. Immediately before and after passive auditory stimulation as well as after a period of recovery, patients completed a simple visual task requiring detection of light flashes presented along the horizontal plane in total darkness. The results showed that one-time passive auditory stimulation on the side of the blind, but not of the intact, hemifield of patients with hemianopia induced an improvement in visual detections by almost 100% within 30 min after passive auditory stimulation. This enhancement in performance was reversible and was reduced to baseline 1.5 h later. A non-significant trend of a shift of the visual field border toward the blind hemifield was obtained after passive auditory stimulation. These results are compatible with the view that passive auditory stimulation elicited some activation of the residual visual pathways, which are known to be multisensory and may also be sensitive to unimodal auditory stimuli as were used here. DRKS00003577.

  19. Auditory Training for Central Auditory Processing Disorder

    PubMed Central

    Weihing, Jeffrey; Chermak, Gail D.; Musiek, Frank E.

    2015-01-01

    Auditory training (AT) is an important component of rehabilitation for patients with central auditory processing disorder (CAPD). The present article identifies and describes aspects of AT as they relate to applications in this population. A description of the types of auditory processes along with information on relevant AT protocols that can be used to address these specific deficits is included. Characteristics and principles of effective AT procedures also are detailed in light of research that reflects on their value. Finally, research investigating AT in populations who show CAPD or present with auditory complaints is reported. Although efficacy data in this area are still emerging, current findings support the use of AT for treatment of auditory difficulties. PMID:27587909

  20. Representation of speech in human auditory cortex: is it special?

    PubMed

    Steinschneider, Mitchell; Nourski, Kirill V; Fishman, Yonatan I

    2013-11-01

    Successful categorization of phonemes in speech requires that the brain analyze the acoustic signal along both spectral and temporal dimensions. Neural encoding of the stimulus amplitude envelope is critical for parsing the speech stream into syllabic units. Encoding of voice onset time (VOT) and place of articulation (POA), cues necessary for determining phonemic identity, occurs within shorter time frames. An unresolved question is whether the neural representation of speech is based on processing mechanisms that are unique to humans and shaped by learning and experience, or is based on rules governing general auditory processing that are also present in non-human animals. This question was examined by comparing the neural activity elicited by speech and other complex vocalizations in primary auditory cortex of macaques, who are limited vocal learners, with that in Heschl's gyrus, the putative location of primary auditory cortex in humans. Entrainment to the amplitude envelope is neither specific to humans nor to human speech. VOT is represented by responses time-locked to consonant release and voicing onset in both humans and monkeys. Temporal representation of VOT is observed both for isolated syllables and for syllables embedded in the more naturalistic context of running speech. The fundamental frequency of male speakers is represented by more rapid neural activity phase-locked to the glottal pulsation rate in both humans and monkeys. In both species, the differential representation of stop consonants varying in their POA can be predicted by the relationship between the frequency selectivity of neurons and the onset spectra of the speech sounds. These findings indicate that the neurophysiology of primary auditory cortex is similar in monkeys and humans despite their vastly different experience with human speech, and that Heschl's gyrus is engaged in general auditory, and not language-specific, processing. This article is part of a Special Issue entitled

  1. Slope Transit Time (STT): A Pulse Transit Time Proxy requiring Only a Single Signal Fiducial Point.

    PubMed

    Addison, Paul S

    2016-11-01

    A novel pulse transit time proxy measurement, slope transit time (STT), is proposed in this letter. STT is based on geometrical considerations of the arriving photoplethysmographic cardiac waveform and its computation requires only the measurement of a single point on each cardiac beat arriving at the peripheral site. This novel transit time is explained conceptually and its implementation illustrated through its application to signals from respiratory effort, Müller maneuver, and obstructive sleep apnea trials.

  2. A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis

    PubMed Central

    Chen, Qian; Zhang, Nailing; Gray, Ryan S.; Li, Huili; Ewald, Andrew J.; Zahnow, Cynthia A.; Pan, Duojia

    2014-01-01

    Despite recent progress, the physiological role of Hippo signaling in mammary gland development and tumorigenesis remains poorly understood. Here we show that the Hippo pathway is functionally dispensable in virgin mammary glands but specifically required during pregnancy. In contrast to many other tissues, hyperactivation of YAP in mammary epithelia does not induce hyperplasia but leads to defects in terminal differentiation. Interestingly, loss of YAP causes no obvious defects in virgin mammary glands but potently suppresses oncogene-induced mammary tumors. The selective requirement for YAP in oncogenic growth highlights the potential of YAP inhibitors as molecular targeted therapies against breast cancers. PMID:24589775

  3. Tomato susceptibility to root-knot nematodes requires an intact jasmonic acid signaling pathway.

    PubMed

    Bhattarai, Kishor K; Xie, Qi-Guang; Mantelin, Sophie; Bishnoi, Usha; Girke, Thomas; Navarre, Duroy A; Kaloshian, Isgouhi

    2008-09-01

    Responses of resistant (Mi-1/Mi-1) and susceptible (mi-1/ mi-1) tomato (Solanum lycopersicum) to root-knot nematodes (RKNs; Meloidogyne spp.) infection were monitored using cDNA microarrays, and the roles of salicylic acid (SA) and jasmonic acid (JA) defense signaling were evaluated in these interactions. Array analysis was used to compare transcript profiles in incompatible and compatible interactions of tomato roots 24 h after RKN infestation. The jai1 and def1 tomato mutant, altered in JA signaling, and tomato transgenic line NahG, altered in SA signaling, in the presence or absence of the RKN resistance gene Mi-1, were evaluated. The array analysis identified 1,497 and 750 genes differentially regulated in the incompatible and compatible interactions, respectively. Of the differentially regulated genes, 37% were specific to the incompatible interactions. NahG affected neither Mi-1 resistance nor basal defenses to RKNs. However, jai1 reduced tomato susceptibility to RKNs while not affecting Mi-1 resistance. In contrast, the def1 mutant did not affect RKN susceptibility. These results indicate that JA-dependent signaling does not play a role in Mi-1-mediated defense; however, an intact JA signaling pathway is required for tomato susceptibility to RKNs. In addition, low levels of SA might be sufficient for basal and Mi-1 resistance to RKNs.

  4. Kit signaling is required for development of coordinated motility patterns in zebrafish gastrointestinal tract.

    PubMed

    Rich, Adam; Gordon, Scott; Brown, Chris; Gibbons, Simon J; Schaefer, Katherine; Hennig, Grant; Farrugia, Gianrico

    2013-06-01

    Interstitial cells of Cajal (ICC) provide a pacemaker signal for coordinated motility patterns in the mammalian gastrointestinal (GI) tract. Kit signaling is required for development and maintenance of ICC, and these cells can be identified by Kit-like immunoreactivity. The zebrafish GI tract has two distinct ICC networks similar to mammals, suggesting a similar role in the generation of GI motility; however, a functional role for Kit-positive cells in zebrafish has not been determined. Analysis of GI motility in intact zebrafish larvae was performed during development and after disruption of Kit signaling. Development of coordinated motility patterns occurred after 5 days post-fertilization (dpf) and correlated with appearance of Kit-positive cells. Disruptions of Kit signaling using the Kit antagonist imatinib mesylate, and in Sparse, a null kita mutant, also disrupted development of coordinated motility patterns. These data suggest that Kit signaling is necessary for development of coordinated motility patterns and that Kit-positive cells in zebrafish are necessary for coordinated motility patterns.

  5. Cardiomyocyte FGF signaling is required for Cx43 phosphorylation and cardiac gap junction maintenance.

    PubMed

    Sakurai, Takashi; Tsuchida, Mariko; Lampe, Paul D; Murakami, Masahiro

    2013-08-15

    Cardiac remodeling resulting from impairment of myocardial integrity leads to heart failure, through still incompletely understood mechanisms. The fibroblast growth factor (FGF) system has been implicated in tissue maintenance, but its role in the adult heart is not well defined. We hypothesized that the FGF system plays a role in the maintenance of cardiac homeostasis, and the impairment of cardiomyocyte FGF signaling leads to pathological cardiac remodeling. We showed that FGF signaling is required for connexin 43 (Cx43) localization at cell-cell contacts in isolated cardiomyocytes and COS7 cells. Lack of FGF signaling led to decreased Cx43 phosphorylation at serines 325/328/330 (S325/328/330), sites known to be important for assembly of gap junctions. Cx43 instability induced by FGF inhibition was restored by the Cx43 S325/328/330 phospho-mimetic mutant, suggesting FGF-dependent phosphorylation of these sites. Consistent with these in vitro findings, cardiomyocyte-specific inhibition of FGF signaling in adult mice demonstrated mislocalization of Cx43 at intercalated discs, whereas localization of N-cadherin and desmoplakin was not affected. This led to premature death resulting from impaired cardiac remodeling. We conclude that cardiomyocyte FGF signaling is essential for cardiomyocyte homeostasis through phosphorylation of Cx43 at S325/328/330 residues which are important for the maintenance of gap junction.

  6. Fgf Signaling is Required for Photoreceptor Maintenance in the Adult Zebrafish Retina

    PubMed Central

    Hochmann, Sarah; Kaslin, Jan; Hans, Stefan; Weber, Anke; Machate, Anja; Geffarth, Michaela; Funk, Richard H. W.; Brand, Michael

    2012-01-01

    Fibroblast growth factors (Fgf) are secreted signaling molecules that have mitogenic, patterning, neurotrophic and angiogenic properties. Their importance during embryonic development in patterning and morphogenesis of the vertebrate eye is well known, but less is known about the role of Fgfs in the adult vertebrate retina. To address Fgf function in adult retina, we determined the spatial distribution of components of the Fgf signaling pathway in the adult zebrafish retina. We detected differential expression of Fgf receptors, ligands and downstream Fgf targets within specific retinal layers. Furthermore, we blocked Fgf signaling in the retina, by expressing a dominant negative variant of Fgf receptor 1 conditionally in transgenic animals. After blocking Fgf signaling we observe a fast and progressive photoreceptor degeneration and disorganization of retinal tissue, coupled with cell death in the outer nuclear layer. Following the degeneration of photoreceptors, a profound regeneration response is triggered that starts with proliferation in the inner nuclear layer. Ultimately, rod and cone photoreceptors are regenerated completely. Our study reveals the requirement of Fgf signaling to maintain photoreceptors and for proliferation during regeneration in the adult zebrafish retina. PMID:22291943

  7. Fgf signaling is required for photoreceptor maintenance in the adult zebrafish retina.

    PubMed

    Hochmann, Sarah; Kaslin, Jan; Hans, Stefan; Weber, Anke; Machate, Anja; Geffarth, Michaela; Funk, Richard H W; Brand, Michael

    2012-01-01

    Fibroblast growth factors (Fgf) are secreted signaling molecules that have mitogenic, patterning, neurotrophic and angiogenic properties. Their importance during embryonic development in patterning and morphogenesis of the vertebrate eye is well known, but less is known about the role of Fgfs in the adult vertebrate retina. To address Fgf function in adult retina, we determined the spatial distribution of components of the Fgf signaling pathway in the adult zebrafish retina. We detected differential expression of Fgf receptors, ligands and downstream Fgf targets within specific retinal layers. Furthermore, we blocked Fgf signaling in the retina, by expressing a dominant negative variant of Fgf receptor 1 conditionally in transgenic animals. After blocking Fgf signaling we observe a fast and progressive photoreceptor degeneration and disorganization of retinal tissue, coupled with cell death in the outer nuclear layer. Following the degeneration of photoreceptors, a profound regeneration response is triggered that starts with proliferation in the inner nuclear layer. Ultimately, rod and cone photoreceptors are regenerated completely. Our study reveals the requirement of Fgf signaling to maintain photoreceptors and for proliferation during regeneration in the adult zebrafish retina.

  8. Direct and indirect requirements of Shh/Gli signaling in early pituitary development.

    PubMed

    Wang, Yiwei; Martin, James F; Bai, C Brian

    2010-12-15

    Induction of early pituitary progenitors is achieved through combined activities of signals from adjacent embryonic tissues. Previous studies have identified a requirement for oral ectoderm derived Sonic Hedgehog (Shh) in specification and/or proliferation of early pituitary progenitors, however how different Gli genes mediate Shh signaling to control pituitary progenitor development has not yet been determined. Here we show that Gli2, which encodes a major Gli activator, is required for proliferation of specific groups of pituitary progenitors but not for initial dorsoventral patterning. We further show that the action of Gli2 occurs prior to the closure of Rathke' pouch. Lastly, we show that Shh/Gli2 signaling controls the diencephalic expression of Bone morphogenetic protein 4 (Bmp4) and Fibroblast growth factor 8 (Fgf8), two genes that are known to play critical roles in patterning and growth of Rathke's pouch. Our results therefore suggest both cell-autonomous and non-cell-autonomous requirements for Gli2 in regulation of pituitary progenitor specification, proliferation and differentiation. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Glucose phosphorylation is required for insulin-dependent mTOR signalling in the heart

    PubMed Central

    Sharma, Saumya; Guthrie, Patrick; Chan, Suzanne; Haq, Syed; Taegtmeyer, Heinrich

    2008-01-01

    Objective: Insulin regulates both glucose uptake and postnatal cardiac growth. The anabolic effects of insulin are mediated by the mammalian target of rapamycin (mTOR), an evolutionarily conserved kinase which is also a convergence point between nutrient sensing and cell growth. We postulated that mTOR signalling in the heart requires the metabolism of glucose. Methods: We interrogated the insulin-mediated mTOR signalling pathway in response to different metabolic interventions regulating substrate metabolism in the isolated working rat heart and in isolated cardiomyocytes. Results: Although insulin enhanced Akt activity, phosphorylation of mTOR and its downstream targets (p70S6K and 4EBP1) required the addition of glucose. Glucose-dependent p70S6K phosphorylation was independent of the hexosamine biosynthetic pathway, the AMP kinase pathway, and the pentose phosphate pathway. However, inhibition of glycolysis downstream of hexokinase markedly enhanced p70S6K phosphorylation. Furthermore, 2-deoxyglucose activated p70S6K suggesting that phosphorylation of glucose is required for carbohydrate-mediated mTOR signalling in the heart. Lastly, we also found enhanced p70S6K phosphorylation in the hearts of diabetic rats. Conclusion: Phosphorylation of glucose is necessary for insulin-dependent mTOR activity in the heart, suggesting a link between intermediary metabolism and cardiac growth. PMID:17553476

  10. Neuroglobin expression in the mammalian auditory system

    PubMed Central

    Reuss, Stefan; Banica, Ovidiu; Elgurt, Mirra; Mitz, Stephanie; Disque-Kaiser, Ursula; Riemann, Randolf; Hill, Marco; Jaquish, Dawn V.; Koehrn, Fred J.; Burmester, Thorsten; Hankeln, Thomas; Woolf, Nigel K.

    2015-01-01

    The energy-yielding pathways that provide the large amounts of metabolic energy required by inner ear sensorineural cells are poorly understood. Neuroglobin (Ngb) is a neuron-specific hemoprotein of the globin family, which is suggested to be involved in oxidative energy metabolism. Here we present quantitative real-time reverse transcription PCR, in situ hybridization, immunohistochemical and Western blot evidence that neuroglobin is highly expressed in the mouse and rat cochlea. For primary cochlea neurons, Ngb expression is limited to the subpopulation of type I spiral ganglion cells, those which innervate inner hair cells, while the subpopulation of type II spiral ganglion cells which innervate the outer hair cells do not express Ngb. We further investigated Ngb distribution in rat, mouse and human auditory brainstem centers, and found that the cochlear nuclei and superior olivary complex (SOC) also express considerable amounts of Ngb. Notably, the majority of olivocochlear neurons, those which provide efferent innervation of outer hair cells as identified by neuronal tract tracing, were Ngb-immunoreactive. We also observed that neuroglobin in the SOC frequently co-localized with neuronal nitric oxide synthase, the enzyme responsible for nitric oxide production. Our findings suggest that neuroglobin is well positioned to play an important physiologic role in the oxygen homeostasis of the peripheral and central auditory nervous system, and provides the first evidence that Ngb signal differentiates the central projections of the inner and outer hair cells. PMID:25636685

  11. Neuroglobin Expression in the Mammalian Auditory System.

    PubMed

    Reuss, Stefan; Banica, Ovidiu; Elgurt, Mirra; Mitz, Stephanie; Disque-Kaiser, Ursula; Riemann, Randolf; Hill, Marco; Jaquish, Dawn V; Koehrn, Fred J; Burmester, Thorsten; Hankeln, Thomas; Woolf, Nigel K

    2016-04-01

    The energy-yielding pathways that provide the large amounts of metabolic energy required by inner ear sensorineural cells are poorly understood. Neuroglobin (Ngb) is a neuron-specific hemoprotein of the globin family, which is suggested to be involved in oxidative energy metabolism. Here, we present quantitative real-time reverse transcription PCR, in situ hybridization, immunohistochemical, and Western blot evidence that neuroglobin is highly expressed in the mouse and rat cochlea. For primary cochlea neurons, Ngb expression is limited to the subpopulation of type I spiral ganglion cells, those which innervate inner hair cells, while the subpopulation of type II spiral ganglion cells which innervate the outer hair cells do not express Ngb. We further investigated Ngb distribution in rat, mouse, and human auditory brainstem centers, and found that the cochlear nuclei and superior olivary complex (SOC) also express considerable amounts of Ngb. Notably, the majority of olivocochlear neurons, those which provide efferent innervation of outer hair cells as identified by neuronal tract tracing, were Ngb-immunoreactive. We also observed that neuroglobin in the SOC frequently co-localized with neuronal nitric oxide synthase, the enzyme responsible for nitric oxide production. Our findings suggest that neuroglobin is well positioned to play an important physiologic role in the oxygen homeostasis of the peripheral and central auditory nervous system, and provides the first evidence that Ngb signal differentiates the central projections of the inner and outer hair cells.

  12. Loss of Kv3.1 tonotopicity and alterations in cAMP response element-binding protein signaling in central auditory neurons of hearing impaired mice.

    PubMed

    von Hehn, Christian A A; Bhattacharjee, Arin; Kaczmarek, Leonard K

    2004-02-25

    The promoter for the kv3.1 potassium channel gene is regulated by a Ca2+-cAMP responsive element, which binds the transcription factor cAMP response element-binding protein (CREB). Kv3.1 is expressed in a tonotopic gradient within the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem, where Kv3.1 levels are highest at the medial end, which corresponds to high auditory frequencies. We have compared the levels of Kv3.1, CREB, and the phosphorylated form of CREB (pCREB) in a mouse strain that maintains good hearing throughout life, CBA/J (CBA), with one that suffers early cochlear hair cell loss, C57BL/6 (BL/6). A gradient of Kv3.1 immunoreactivity in the MNTB was detected in both young (6 week) and older (8 month) CBA mice. Although no gradient of CREB was detected, pCREB-immunopositive cells were grouped together in distinct clusters along the tonotopic axis. The same pattern of Kv3.1, CREB, and pCREB localization was also found in young BL/6 mice at a time (6 weeks) when hearing is normal. In contrast, at 8 months, when hearing is impaired, the gradient of Kv3.1 was abolished. Moreover, in the older BL/6 mice there was a decrease in CREB expression along the tonotopic axis, and the pattern of pCREB labeling appeared random, with no discrete clusters of pCREB-positive cells along the tonotopic axis. Our findings are consistent with the hypothesis that ongoing activity in auditory brainstem neurons is necessary for the maintenance of Kv3.1 tonotopicity through the CREB pathway.

  13. Requirement for non-regulated, constitutive calcium influx in macrophage survival signaling

    SciTech Connect

    Tano, Jean-Yves; Vazquez, Guillermo

    2011-04-08

    Highlights: {yields} We examine the role of constitutive Ca{sup 2+} influx in macrophage survival. {yields} Survival signaling exhibits a mandatory requirement for constitutive Ca{sup 2+} influx. {yields} CAM/CAMKII couples constitutive Ca{sup 2+} influx to survival signaling. -- Abstract: The phosphatidylinositol-3-kinase (PI3K)/AKT axis and the Nuclear Factor kappa B (NF{kappa}B) pathway play critical roles in macrophage survival. In cells other than macrophages proper operation of those two pathways requires Ca{sup 2+} influx into the cell, but if that is the case in macrophages remains unexplored. In the present work we used THP-1-derived macrophages and a pharmacological approach to examine for the first time the role of constitutive, non-regulated Ca{sup 2+} influx in PI3K/AKT and NF{kappa}B signaling. Blocking constitutive function of Ca{sup 2+}-permeable channels with the organic channel blocker SKF96365 completely prevented phosphorylation of I{kappa}B{alpha}, AKT and its downstream target BAD in TNF{alpha}-treated macrophages. A similar effect was observed upon treating macrophages with the calmodulin (CAM) inhibitor W-7 or the calmodulin-dependent kinase II (CAMKII) inhibitor KN-62. In addition, pre-treating macrophages with SKF96365 significantly enhanced TNF{alpha}-induced apoptosis. Our findings suggest that in THP-1-derived macrophages survival signaling depends, to a significant extent, on constitutive Ca{sup 2+} influx presumably through a mechanism that involves the CAM/CAMKII axis as a coupling component between constitutive Ca{sup 2+} influx and activation of survival signaling.

  14. Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions

    PubMed Central

    Sheridan, David C.; Takekura, Hiroaki; Franzini-Armstrong, Clara; Beam, Kurt G.; Allen, Paul D.; Perez, Claudio F.

    2006-01-01

    We have defined regions of the skeletal muscle ryanodine receptor (RyR1) essential for bidirectional signaling with dihydropyridine receptors (DHPRs) and for the organization of DHPR into tetrad arrays by expressing RyR1–RyR3 chimerae in dyspedic myotubes. RyR1–RyR3 constructs bearing RyR1 residues 1–1681 restored wild-type DHPR tetrad arrays and, in part, skeletal-type excitation–contraction (EC) coupling (orthograde signaling) but failed to enhance DHPR Ca2+ currents (retrograde signaling) to WT RyR1 levels. Within this region, the D2 domain (amino acids 1272–1455), although ineffective on its own, dramatically enhanced the formation of tetrads and EC coupling rescue by constructs that otherwise are only partially effective. These findings suggest that the orthograde signal and DHPR tetrad formation require the contributions of numerous RyR regions. Surprisingly, we found that RyR3, although incapable of supporting EC coupling or tetrad formation, restored a significant level of Ca2+ current, revealing a functional interaction with the skeletal muscle DHPR. Thus, our data support the hypotheses that (i) the structural/functional link between RyR1 and the skeletal muscle DHPR requires multiple interacting regions, (ii) the D2 domain of RyR1 plays a key role in stabilizing this interaction, and (iii) a form of retrograde signaling from RyR3 to the DHPR occurs in the absence of direct protein–protein interactions. PMID:17172444

  15. A Subset of Cholinergic Mushroom Body Neurons Requires Go Signaling to Regulate Sleep in Drosophila

    PubMed Central

    Yi, Wei; Zhang, Yunpeng; Tian, Yinjun; Guo, Jing; Li, Yan; Guo, Aike

    2013-01-01

    Study Objectives: Identifying the neurochemistry and neural circuitry of sleep regulation is critical for understanding sleep and various sleep disorders. Fruit flies display sleep-like behavior, sharing essential features with sleep of vertebrate. In the fruit fly's central brain, the mushroom body (MB) has been highlighted as a sleep center; however, its neurochemical nature remains unclear, and whether it promotes sleep or wake is still a topic of controversy. Design: We used a video recording system to accurately monitor the locomotor activity and sleep status. Gene expression was temporally and regionally manipulated by heat induction and the Gal4/UAS system. Measurements and Results: We found that expressing pertussis toxin (PTX) in the MB by c309-Gal4 to block Go activity led to unique sleep defects as dramatic sleep increase in daytime and fragmented sleep in nighttime. We narrowed down the c309-Gal4 expressing brain regions to the MB α/β core neurons that are responsible for the Go-mediated sleep effects. Using genetic tools of neurotransmitter-specific Gal80 and RNA interference approach to suppress acetylcholine signal, we demonstrated that these MB α/β core neurons were cholinergic and sleep-promoting neurons, supporting that Go mediates an inhibitory signal. Interestingly, we found that adjacent MB α/β neurons were also cholinergic but wake-promoting neurons, in which Go signal was also required. Conclusion: Our findings in fruit flies characterized a group of sleep-promoting neurons surrounded by a group of wake-promoting neurons. The two groups of neurons are both cholinergic and use Go inhibitory signal to regulate sleep. Citation: Yi W; Zhang Y; Tian Y; Guo J; Li Y; Guo A. A subset of cholinergic mushroom body neurons requires go signaling to regulate sleep in Drosophila. SLEEP 2013;36(12):1809-1821. PMID:24293755

  16. Functional imaging of auditory scene analysis.

    PubMed

    Gutschalk, Alexander; Dykstra, Andrew R

    2014-01-01

    Our auditory system is constantly faced with the task of decomposing the complex mixture of sound arriving at the ears into perceptually independent streams constituting accurate representations of individual sound sources. This decomposition, termed auditory scene analysis, is critical for both survival and communication, and is thought to underlie both speech and music perception. The neural underpinnings of auditory scene analysis have been studied utilizing invasive experiments with animal models as well as non-invasive (MEG, EEG, and fMRI) and invasive (intracranial EEG) studies conducted with human listeners. The present article reviews human neurophysiological research investigating the neural basis of auditory scene analysis, with emphasis on two classical paradigms termed streaming and informational masking. Other paradigms - such as the continuity illusion, mistuned harmonics, and multi-speaker environments - are briefly addressed thereafter. We conclude by discussing the emerging evidence for the role of auditory cortex in remapping incoming acoustic signals into a perceptual representation of auditory streams, which are then available for selective attention and further conscious processing. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

  17. Magnetic resonance imaging of the internal auditory canal

    SciTech Connect

    Daniels, D.L.; Herfkins, R.; Koehler, P.R.; Millen, S.J.; Shaffer, K.A.; Williams, A.L.; Haughton, V.M.

    1984-04-01

    Three patients with exclusively or predominantly intracanalicular neuromas and 5 with presumably normal internal auditory canals were examined with prototype 1.4- or 1.5-tesla magnetic resonance (MR) scanners. MR images showed the 7th and 8th cranial nerves in the internal auditory canal. The intracanalicular neuromas had larger diameter and slightly greater signal strength than the nerves. Early results suggest that minimal enlargement of the nerves can be detected even in the internal auditory canal.

  18. ER Alpha Rapid Signaling Is Required for Estrogen Induced Proliferation and Migration of Vascular Endothelial Cells

    PubMed Central

    Lu, Qing; Schnitzler, Gavin R.; Ueda, Kazutaka; Iyer, Lakshmanan K.; Diomede, Olga I.; Andrade, Tiffany; Karas, Richard H.

    2016-01-01

    Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs), which likely underlies its ability to accelerate re-endothelialization and reduce adverse remodeling after vascular injury. In previous studies, we have shown that the protective effects of E2 (the active endogenous form of estrogen) in vascular injury require the estrogen receptor alpha (ERα). ERα transduces the effects of estrogen via a classical DNA binding, “genomic” signaling pathway and via a more recently-described “rapid” signaling pathway that is mediated by a subset of ERα localized to the cell membrane. However, which of these pathways mediates the effects of estrogen on endothelial cells is poorly understood. Here we identify a triple point mutant version of ERα (KRR ERα) that is specifically defective in rapid signaling, but is competent to regulate transcription through the “genomic” pathway. We find that in ECs expressing wild type ERα, E2 regulates many genes involved in cell migration and proliferation, promotes EC migration and proliferation, and also blocks the adhesion of monocytes to ECs. ECs expressing KRR mutant ERα, however, lack all of these responses. These observations establish KRR ERα as a novel tool that could greatly facilitate future studies into the vascular and non-vascular functions of ERα rapid signaling. Further, they support that rapid signaling through ERα is essential for many of the transcriptional and physiological responses of ECs to E2, and that ERα rapid signaling in ECs, in vivo, may be critical for the vasculoprotective and anti-inflammatory effects of estrogen. PMID:27035664

  19. Perceptual Plasticity for Auditory Object Recognition

    PubMed Central

    Heald, Shannon L. M.; Van Hedger, Stephen C.; Nusbaum, Howard C.

    2017-01-01

    In our auditory environment, we rarely experience the exact acoustic waveform twice. This is especially true for communicative signals that have meaning for listeners. In speech and music, the acoustic signal changes as a function of the talker (or instrument), speaking (or playing) rate, and room acoustics, to name a few factors. Yet, despite this acoustic variability, we are able to recognize a sentence or melody as the same across various kinds of acoustic inputs and determine meaning based on listening goals, expectations, context, and experience. The recognition process relates acoustic signals to prior experience despite variability in signal-relevant and signal-irrelevant acoustic properties, some of which could be considered as “noise” in service of a recognition goal. However, some acoustic variability, if systematic, is lawful and can be exploited by listeners to aid in recognition. Perceivable changes in systematic variability can herald a need for listeners to reorganize perception and reorient their attention to more immediately signal-relevant cues. This view is not incorporated currently in many extant theories of auditory perception, which traditionally reduce psychological or neural representations of perceptual objects and the processes that act on them to static entities. While this reduction is likely done for the sake of empirical tractability, such a reduction may seriously distort the perceptual process to be modeled. We argue that perceptual representations, as well as the processes underlying perception, are dynamically determined by an interaction between the uncertainty of the auditory signal and constraints of context. This suggests that the process of auditory recognition is highly context-dependent in that the identity of a given auditory object may be intrinsically tied to its preceding context. To argue for the flexible neural and psychological updating of sound-to-meaning mappings across speech and music, we draw upon examples

  20. Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca

    PubMed Central

    Kovacevic, Ismar; Orozco, Jose M.; Cram, Erin J.

    2013-01-01

    The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue. PMID:23671426

  1. Notch signal reception is required in vascular smooth muscle cells for ductus arteriosus closure

    PubMed Central

    Krebs, Luke T.; Norton, Christine R.; Gridley, Thomas

    2017-01-01

    Summary The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus, and is one of the most common congenital heart defects. Our previous work demonstrated that vascular smooth muscle cell expression of the Jag1 gene, which encodes a ligand for Notch family receptors, is essential for postnatal closure of the ductus arteriosus in mice. However, it was not known what cell population was responsible for receiving the Jag1-mediated signal. Here we show, using smooth muscle cell-specific deletion of the Rbpj gene, which encodes a transcription factor that mediates all canonical Notch signaling, that Notch signal reception in the vascular smooth muscle cell compartment is required for ductus arteriosus closure. These data indicate that homotypic vascular smooth muscle cell interactions are required for proper contractile smooth muscle cell differentiation and postnatal closure of the ductus arteriosus in mice. PMID:26742650

  2. GLABROUS INFLORESCENCE STEMS (GIS) is required for trichome branching through gibberellic acid signaling in Arabidopsis.

    PubMed

    An, Lijun; Zhou, Zhongjing; Su, Sha; Yan, An; Gan, Yinbo

    2012-02-01

    Cell differentiation generally corresponds to the cell cycle, typically forming a non-dividing cell with a unique differentiated morphology, and Arabidopsis trichome is an excellent model system to study all aspects of cell differentiation. Although gibberellic acid is reported to be involved in trichome branching in Arabidopsis, the mechanism for such signaling is unclear. Here, we demonstrated that GLABROUS INFLORESCENCE STEMS (GIS) is required for the control of trichome branching through gibberellic acid signaling. The phenotypes of a loss-of-function gis mutant and an overexpressor showed that GIS acted as a repressor to control trichome branching. Our results also show that GIS is not required for cell endoreduplication, and our molecular and genetic study results have shown that GIS functions downstream of the key regulator of trichome branching, STICHEL (STI), to control trichome branching through the endoreduplication-independent pathway. Furthermore, our results also suggest that GIS controls trichome branching in Arabidopsis through two different pathways and acts either upstream or downstream of the negative regulator of gibbellic acid signaling SPINDLY (SPY).

  3. Requirement for Pathogenic IL-23 Signaling Is Restricted to Initiation of Autoimmune Myocarditis

    PubMed Central

    Wu, Lei; Diny, Nicola L.; Ong, SuFey; Barin, Jobert G.; Hou, Xuezhou; Rose, Noel R.; Talor, Monica V.; Čiháková, Daniela

    2016-01-01

    Using a mouse model of experimental autoimmune myocarditis (EAM), we showed for the first time that IL-23 stimulation of CD4+ T cells is required only briefly at the initiation of GM-CFS-dependent cardiac autoimmunity. IL-23 signal, acting as a switch, turns on pathogenicity of CD4+ T cells, and becomes dispensable once autoreactivity is established. Il23a−/− mice failed to mount an efficient Th17 response to immunization, and were protected from myocarditis. However, remarkably, transient IL-23 stimulation ex vivo fully restored pathogenicity in otherwise nonpathogenic CD4+ T cells raised from Il23a−/− donors. Thus, IL-23 may no longer be necessary to uphold inflammation in established autoimmune diseases. In addition, we demonstrated that IL-23 induced GM-CSF mediates the pathogenicity of CD4+ T cells in EAM. The neutralization of GM-CSF abrogated cardiac inflammation. However, sustained IL-23 signaling is required to maintain IL-17A production in CD4+ T cells. Despite inducing inflammation in Il23a−/− recipients comparable to WT, autoreactive CD4+ T cells downregulated IL-17A production without persistent IL-23 signaling. This divergence on the controls of GM-CSF-dependent pathogenicity on one side and IL-17A production on the other side may contribute to the discrepant efficacies of anti-IL-23 therapy in different autoimmune diseases. PMID:26660726

  4. Notch signal reception is required in vascular smooth muscle cells for ductus arteriosus closure.

    PubMed

    Krebs, Luke T; Norton, Christine R; Gridley, Thomas

    2016-02-01

    The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus, and is one of the most common congenital heart defects. Our previous work demonstrated that vascular smooth muscle cell expression of the Jag1 gene, which encodes a ligand for Notch family receptors, is essential for postnatal closure of the ductus arteriosus in mice. However, it was not known what cell population was responsible for receiving the Jag1-mediated signal. Here we show, using smooth muscle cell-specific deletion of the Rbpj gene, which encodes a transcription factor that mediates all canonical Notch signaling, that Notch signal reception in the vascular smooth muscle cell compartment is required for ductus arteriosus closure. These data indicate that homotypic vascular smooth muscle cell interactions are required for proper contractile smooth muscle cell differentiation and postnatal closure of the ductus arteriosus in mice. © 2016 Wiley Periodicals, Inc.

  5. Cutting Edge: CD3 ITAM Diversity Is Required for Optimal TCR Signaling and Thymocyte Development.

    PubMed

    Bettini, Matthew L; Chou, Po-Chein; Guy, Clifford S; Lee, Thomas; Vignali, Kate M; Vignali, Dario A A

    2017-09-01

    For the αβ or γδTCR chains to integrate extracellular stimuli into the appropriate intracellular cellular response, they must use the 10 ITAMs found within the CD3 subunits (CD3γε, CD3δε, and ζζ) of the TCR signaling complex. However, it remains unclear whether each specific ITAM sequence of the individual subunit (γεδζ) is required for thymocyte development or whether any particular CD3 ITAM motif is sufficient. In this article, we show that mice utilizing a single ITAM sequence (γ, ε, δ, ζa, ζb, or ζc) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4(-)CD8(-) (double-negative) to CD4(+)CD8(+) (double-positive) maturation because of low TCR expression and signaling. Together, the data suggest that ITAM sequence diversity is required for optimal TCR signal transduction and subsequent T cell maturation. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. Tankyrase Sterile α Motif Domain Polymerization Is Required for Its Role in Wnt Signaling.

    PubMed

    Riccio, Amanda A; McCauley, Michael; Langelier, Marie-France; Pascal, John M

    2016-09-06

    Tankyrase-1 (TNKS1/PARP-5a) is a poly(ADP-ribose) polymerase (PARP) enzyme that regulates multiple cellular processes creating a poly(ADP-ribose) posttranslational modification that can lead to target protein turnover. TNKS1 thereby controls protein levels of key components of signaling pathways, including Axin1, the limiting component of the destruction complex in canonical Wnt signaling that degrades β-catenin to prevent its coactivator function in gene expression. There are limited molecular level insights into TNKS1 regulation in cell signaling pathways. TNKS1 has a sterile α motif (SAM) domain that is known to mediate polymerization, but the functional requirement for SAM polymerization has not been assessed. We have determined the crystal structure of wild-type human TNKS1 SAM domain and used structure-based mutagenesis to disrupt polymer formation and assess the consequences on TNKS1 regulation of β-catenin-dependent transcription. Our data indicate the SAM polymer is critical for TNKS1 catalytic activity and allows TNKS1 to efficiently access cytoplasmic signaling complexes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells.

    PubMed

    Zhang, Baojun; Wu, Jianxuan; Jiao, Yiqun; Bock, Cheryl; Dai, Meifang; Chen, Benny; Chao, Nelson; Zhang, Weiguo; Zhuang, Yuan

    2015-11-01

    Dendritic epidermal T cells (DETCs) are generated exclusively in the fetal thymus and maintained in the skin epithelium throughout postnatal life of the mouse. DETCs have restricted antigenic specificity as a result of their exclusive usage of a canonical TCR. Although the importance of the TCR in DETC development has been well established, the exact role of TCR signaling in DETC homeostasis and function remains incompletely defined. In this study, we investigated TCR signaling in fully matured DETCs by lineage-restricted deletion of the Lat gene, an essential signaling molecule downstream of the TCR. We found that Lat deletion impaired TCR-dependent cytokine gene activation and the ability of DETCs to undergo proliferative expansion. However, linker for activation of T cells-deficient DETCs were able to maintain long-term population homeostasis, although with a reduced proliferation rate. Mice with Lat deletion in DETCs exhibited delayed wound healing accompanied by impaired clonal expansion within the wound area. Our study revealed differential requirements for TCR signaling in homeostatic maintenance of DETCs and in their effector function during wound healing.

  8. Fgf19 regulated by Hh signaling is required for zebrafish forebrain development.

    PubMed

    Miyake, Ayumi; Nakayama, Yoshiaki; Konishi, Morichika; Itoh, Nobuyuki

    2005-12-01

    Fibroblast growth factor (Fgf) signaling plays important roles in brain development. Fgf3 and Fgf8 are crucial for the formation of the forebrain and hindbrain. Fgf8 is also required for the midbrain to form. Here, we identified zebrafish Fgf19 and examined its roles in brain development by knocking down Fgf19 function. We found that Fgf19 expressed in the forebrain, midbrain and hindbrain was involved in cell proliferation and cell survival during embryonic brain development. Fgf19 was also essential for development of the ventral telencephalon and diencephalon. Regional specification is linked to cell type specification. Fgf19 was also essential for the specification of gamma-aminobutyric acid (GABA)ergic interneurons and oligodendrocytes generated in the ventral telencephalon and diencephalon. The cross talk between Fgf and Hh signaling is critical for brain development. In the forebrain, Fgf19 expression was down-regulated on inhibition of Hh but not of Fgf3/Fgf8, and overexpression of Fgf19 rescued partially the phenotype on inhibition of Hh. The present findings indicate that Fgf19 signaling is crucial for forebrain development by interacting with Hh and provide new insights into the roles of Fgf signaling in brain development.

  9. Maturation of a central brain flight circuit in Drosophila requires Fz2/Ca2+ signaling

    PubMed Central

    Agrawal, Tarjani; Hasan, Gaiti

    2015-01-01

    The final identity of a differentiated neuron is determined by multiple signaling events, including activity dependent calcium transients. Non-canonical Frizzled2 (Fz2) signaling generates calcium transients that determine neuronal polarity, neuronal migration, and synapse assembly in the developing vertebrate brain. Here, we demonstrate a requirement for Fz2/Ca2+ signaling in determining the final differentiated state of a set of central brain dopaminergic neurons in Drosophila, referred to as the protocerebral anterior medial (PAM) cluster. Knockdown or inhibition of Fz2/Ca2+ signaling during maturation of the flight circuit in pupae reduces Tyrosine Hydroxylase (TH) expression in the PAM neurons and affects maintenance of flight. Thus, we demonstrate that Fz2/Ca2+ transients during development serve as a pre-requisite for normal adult behavior. Our results support a neural mechanism where PAM neuron send projections to the α' and β' lobes of a higher brain centre, the mushroom body, and function in dopaminergic re-inforcement of flight. DOI: http://dx.doi.org/10.7554/eLife.07046.001 PMID:25955970

  10. A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling

    PubMed Central

    Weatherbee, Scott D.; Niswander, Lee A.; Anderson, Kathryn V.

    2009-01-01

    Meckel syndrome (MKS) is a rare autosomal recessive disease causing perinatal lethality associated with a complex syndrome that includes occipital meningoencephalocele, hepatic biliary ductal plate malformation, postaxial polydactyly and polycystic kidneys. The gene mutated in type 1 MKS encodes a protein associated with the base of the cilium in vertebrates and nematodes. However, shRNA knockdown studies in cell culture have reported conflicting results on the role of Mks1 in ciliogenesis. Here we show that loss of function of mouse Mks1 results in an accurate model of human MKS, with structural abnormalities in the neural tube, biliary duct, limb patterning, bone development and the kidney that mirror the human syndrome. In contrast to cell culture studies, loss of Mks1 in vivo does not interfere with apical localization of epithelial basal bodies but rather leads to defective cilia formation in most, but not all, tissues. Analysis of patterning in the neural tube and the limb demonstrates altered Hedgehog (Hh) pathway signaling underlies some MKS defects, although both tissues show an expansion of the domain of response to Shh signaling, unlike the phenotypes seen in other mutants with cilia loss. Other defects in the skull, lung, rib cage and long bones are likely to be the result of the disruption of Hh signaling, and the basis of defects in the liver and kidney require further analysis. Thus the disruption of Hh signaling can explain many, but not all, of the defects caused by loss of Mks1. PMID:19776033

  11. A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling.

    PubMed

    Weatherbee, Scott D; Niswander, Lee A; Anderson, Kathryn V

    2009-12-01

    Meckel syndrome (MKS) is a rare autosomal recessive disease causing perinatal lethality associated with a complex syndrome that includes occipital meningoencephalocele, hepatic biliary ductal plate malformation, postaxial polydactyly and polycystic kidneys. The gene mutated in type 1 MKS encodes a protein associated with the base of the cilium in vertebrates and nematodes. However, shRNA knockdown studies in cell culture have reported conflicting results on the role of Mks1 in ciliogenesis. Here we show that loss of function of mouse Mks1 results in an accurate model of human MKS, with structural abnormalities in the neural tube, biliary duct, limb patterning, bone development and the kidney that mirror the human syndrome. In contrast to cell culture studies, loss of Mks1 in vivo does not interfere with apical localization of epithelial basal bodies but rather leads to defective cilia formation in most, but not all, tissues. Analysis of patterning in the neural tube and the limb demonstrates altered Hedgehog (Hh) pathway signaling underlies some MKS defects, although both tissues show an expansion of the domain of response to Shh signaling, unlike the phenotypes seen in other mutants with cilia loss. Other defects in the skull, lung, rib cage and long bones are likely to be the result of the disruption of Hh signaling, and the basis of defects in the liver and kidney require further analysis. Thus the disruption of Hh signaling can explain many, but not all, of the defects caused by loss of Mks1.

  12. Sex specific retinoic acid signaling is required for the initiation of urogenital sinus bud development

    PubMed Central

    Bryant, Sarah L.; Francis, Jeffrey C.; Lokody, Isabel B.; Wang, Hong; Risbridger, Gail P.; Loveland, Kate L.; Swain, Amanda

    2014-01-01

    The mammalian urogenital sinus (UGS) develops in a sex specific manner, giving rise to the prostate in the male and the sinus vagina in the embryonic female. Androgens, produced by the embryonic testis, have been shown to be crucial to this process. In this study we show that retinoic acid signaling is required for the initial stages of bud development from the male UGS. Enzymes involved in retinoic acid synthesis are expressed in the UGS mesenchyme in a sex specific manner and addition of ligand to female tissue is able to induce prostate-like bud formation in the absence of androgens, albeit at reduced potency. Functional studies in mouse organ cultures that faithfully reproduce the initiation of prostate development indicate that one of the roles of retinoic acid signaling in the male is to inhibit the expression of Inhba, which encodes the βA subunit of Activin, in the UGS mesenchyme. Through in vivo genetic analysis and culture studies we show that inhibition of Activin signaling in the female UGS leads to a similar phenotype to that of retinoic acid treatment, namely bud formation in the absence of androgens. Our data also reveals that both androgens and retinoic acid have extra independent roles to that of repressing Activin signaling in the development of the prostate during fetal stages. This study identifies a novel role for retinoic acid as a mesenchymal factor that acts together with androgens to determine the position and initiation of bud development in the male UGS epithelia. PMID:25261715

  13. Does the whistling thorn acacia (Acacia drepanolobium) use auditory aposematism to deter mammalian herbivores?

    PubMed

    Lev-Yadun, Simcha

    2016-08-02

    Auditory signaling including aposematism characterizes many terrestrial animals. Auditory aposematism by which certain animals use auditory aposematic signals to fend off enemies is well known for instance in rattlesnakes. Auditory signaling by plants toward animals and other plants is an emerging area of plant biology that still suffers from limited amount of solid data. Here I propose that auditory aposematism operates in the African whistling thorn acacia (Acacia drepanolobium = Vachellia drepanolobium). In this tree, the large and hollow thorn bases whistle when wind blows. This type of aposematism compliments the well-known conspicuous thorn and mutualistic ant based aposematism during day and may operate during night when the conspicuous thorns are invisible.

  14. Auditory scene analysis and sensory memory: the role of the auditory N100m.

    PubMed

    May, P J C; Tiitinen, H

    2004-11-30

    We consider the neural dynamics underlying auditory streaming, the perceptual grouping of transient auditory events, by using neural modeling and magnetoencephalographic (MEG) measurements in humans. We demonstrate that spatial variations in the strength of feedback inhibition leads to differential amplitude modulation (AM) tuning resembling that found in animal models. In our model, neurons respond selectively to stimuli presented at different onset-to-onset interstimulus intervals (ISIs), and their summed activity (corresponding to the MEG signal) exhibits both transient and sustained responses (SRs) at fast ISIs. In MEG measurements utilizing 2-s trains of 50-ms stimuli presented at 0-1950 ms ISIs, we observed the transient N100m and SRs predicted by the model, with a prominent SR emerging for discrete stimuli at ISIs below 200 ms. Our results explain why, at fast stimulus rates, the amplitude of the auditory N100m appears to be strongly attenuated even though auditory cortex continues to respond vigorously to the stimuli. The results suggest that the longer and shorter forms of auditory sensory memory may be reflected in the N100m and the SR, respectively. As the emergence of the SR coincides with the stimuli being perceived as auditory streams, our study suggests that auditory sensory memory as indexed by transient and sustained cortical activity might underlie auditory scene analysis.

  15. Activation of Heschl's gyrus during auditory hallucinations.

    PubMed

    Dierks, T; Linden, D E; Jandl, M; Formisano, E; Goebel, R; Lanfermann, H; Singer, W

    1999-03-01

    Apart from being a common feature of mental illness, auditory hallucinations provide an intriguing model for the study of internally generated sensory perceptions that are attributed to external sources. Until now, the knowledge about the cortical network that supports such hallucinations has been restricted by methodological limitations. Here, we describe an experiment with paranoid schizophrenic patients whose on- and offset of auditory hallucinations could be monitored within one functional magnetic resonance imaging (fMRI) session. We demonstrate an increase of the blood oxygen level-dependent (BOLD) signal in Heschl's gyrus during the patients' hallucinations. Our results provide direct evidence of the involvement of primary auditory areas in auditory verbal hallucinations and establish novel constraints for psychopathological models.

  16. Domain requirements for the Dock adapter protein in growth- cone signaling.

    PubMed

    Rao, Y; Zipursky, S L

    1998-03-03

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

  17. Domain requirements for the Dock adapter protein in growth- cone signaling

    PubMed Central

    Rao, Yong; Zipursky, S. Lawrence

    1998-01-01

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons. PMID:9482841

  18. Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning.

    PubMed

    Khokha, Mustafa K; Hsu, David; Brunet, Lisa J; Dionne, Marc S; Harland, Richard M

    2003-07-01

    During limb outgrowth, signaling by bone morphogenetic proteins (BMPs) must be moderated to maintain the signaling loop between the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER). Gremlin, an extracellular Bmp antagonist, has been proposed to fulfill this function and therefore be important in limb patterning. We tested this model directly by mutating the mouse gene encoding gremlin (Cktsf1b1, herein called gremlin). In the mutant limb, the feedback loop between the ZPA and the AER is interrupted, resulting in abnormal skeletal pattern. We also show that the gremlin mutation is allelic to the limb deformity mutation (ld). Although Bmps and their antagonists have multiple roles in limb development, these experiments show that gremlin is the principal BMP antagonist required for early limb outgrowth and patterning.

  19. Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival.

    PubMed

    Coleman, Jonathan A; Zhu, Xianjun; Djajadi, Hidayat R; Molday, Laurie L; Smith, Richard S; Libby, Richard T; John, Simon W M; Molday, Robert S

    2014-03-01

    ATP8A2 is a P4-ATPase that is highly expressed in the retina, brain, spinal cord and testes. In the retina, ATP8A2 is localized in photoreceptors where it uses ATP to transport phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the exoplasmic to the cytoplasmic leaflet of membranes. Although mutations in ATP8A2 have been reported to cause mental retardation in humans and degeneration of spinal motor neurons in mice, the role of ATP8A2 in sensory systems has not been investigated. We have analyzed the retina and cochlea of ATP8A2-deficient mice to determine the role of ATP8A2 in visual and auditory systems. ATP8A2-deficient mice have shortened photoreceptor outer segments, a reduction in photoresponses and decreased photoreceptor viability. The ultrastructure and phagocytosis of the photoreceptor outer segment appeared normal, but the PS and PE compositions were altered and the rhodopsin content was decreased. The auditory brainstem response threshold was significantly higher and degeneration of spiral ganglion cells was apparent. Our studies indicate that ATP8A2 plays a crucial role in photoreceptor and spiral ganglion cell function and survival by maintaining phospholipid composition and contributing to vesicle trafficking.

  20. Hedgehog signaling is required at multiple stages of zebrafish tooth development

    PubMed Central

    2010-01-01

    Background The accessibility of the developing zebrafish pharyngeal dentition makes it an advantageous system in which to study many aspects of tooth development from early initiation to late morphogenesis. In mammals, hedgehog signaling is known to be essential for multiple stages of odontogenesis; however, potential roles for the pathway during initiation of tooth development or in later morphogenesis are incompletely understood. Results We have identified mRNA expression of the hedgehog ligands shha and the receptors ptc1 and ptc2 during zebrafish pharyngeal tooth development. We looked for, but did not detect, tooth germ expression of the other known zebrafish hedgehog ligands shhb, dhh, ihha, or ihhb, suggesting that as in mammals, only Shh participates in zebrafish tooth development. Supporting this idea, we found that morphological and gene expression evidence of tooth initiation is eliminated in shha mutant embryos, and that morpholino antisense oligonucleotide knockdown of shha, but not shhb, function prevents mature tooth formation. Hedgehog pathway inhibition with the antagonist compound cyclopamine affected tooth formation at each stage in which we applied it: arresting development at early stages and disrupting mature tooth morphology when applied later. These results suggest that hedgehog signaling is required continuously during odontogenesis. In contrast, over-expression of shha had no effect on the developing dentition, possibly because shha is normally extensively expressed in the zebrafish pharyngeal region. Conclusion We have identified previously unknown requirements for hedgehog signaling for early tooth initiation and later morphogenesis. The similarity of our results with data from mouse and other vertebrates suggests that despite gene duplication and changes in the location of where teeth form, the roles of hedgehog signaling in tooth development have been largely conserved during evolution. PMID:21118524

  1. Gibberellin Signaling Requires Chromatin Remodeler PICKLE to Promote Vegetative Growth and Phase Transitions1[OPEN

    PubMed Central

    Nguyen, Khoa Thi; Ogas, Joe; Choi, Giltsu

    2017-01-01

    PICKLE (PKL) is an ATP-dependent chromodomain-helicase-DNA-binding domain (CHD3) chromatin remodeling enzyme in Arabidopsis (Arabidopsis thaliana). Previous studies showed that PKL promotes embryonic-to-vegetative transition by inhibiting expression of seed-specific genes during seed germination. The pkl mutants display a low penetrance of the “pickle root” phenotype, with a thick and green primary root that retains embryonic characteristics. The penetrance of this pickle root phenotype in pkl is dramatically increased in gibberellin (GA)-deficient conditions. At adult stages, the pkl mutants are semidwarfs with delayed flowering time, which resemble reduced GA-signaling mutants. These findings suggest that PKL may play a positive role in regulating GA signaling. A recent biochemical analysis further showed that PKL and GA signaling repressors DELLAs antagonistically regulate hypocotyl cell elongation genes by direct protein-protein interaction. To elucidate further the role of PKL in GA signaling and plant development, we studied the genetic interaction between PKL and DELLAs using the hextuple mutant containing pkl and della pentuple (dP) mutations. Here, we show that PKL is required for most of GA-promoted developmental processes, including vegetative growth such as hypocotyl, leaf, and inflorescence stem elongation, and phase transitions such as juvenile-to-adult leaf and vegetative-to-reproductive phase. The removal of all DELLA functions (in the dP background) cannot rescue these phenotypes in pkl. RNA-sequencing analysis using the ga1 (a GA-deficient mutant), pkl, and the ga1 pkl double mutant further shows that expression of 80% of GA-responsive genes in seedlings is PKL dependent, including genes that function in cell elongation, cell division, and phase transitions. These results indicate that the CHD3 chromatin remodeler PKL is required for regulating gene expression during most of GA-regulated developmental processes. PMID:28057895

  2. Dll1- and Dll4-mediated Notch signaling is required for homeostasis of intestinal stem cells

    PubMed Central

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H.; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-01-01

    Background & Aims Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors, due to their conversion into post-mitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SC), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiological ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Methods Trasgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ERT2). Results Notch1 signaling was found to be activated in intestinal SC. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into post-mitotic goblet cells, concomitant with loss of SC (Olfm4+, Lgr5+ and Ascl2+). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Conclusions Notch signaling in SC and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SC. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. PMID:21238454

  3. Hedgehog signaling is required at multiple stages of zebrafish tooth development.

    PubMed

    Jackman, William R; Yoo, James J; Stock, David W

    2010-11-30

    The accessibility of the developing zebrafish pharyngeal dentition makes it an advantageous system in which to study many aspects of tooth development from early initiation to late morphogenesis. In mammals, hedgehog signaling is known to be essential for multiple stages of odontogenesis; however, potential roles for the pathway during initiation of tooth development or in later morphogenesis are incompletely understood. We have identified mRNA expression of the hedgehog ligands shha and the receptors ptc1 and ptc2 during zebrafish pharyngeal tooth development. We looked for, but did not detect, tooth germ expression of the other known zebrafish hedgehog ligands shhb, dhh, ihha, or ihhb, suggesting that as in mammals, only Shh participates in zebrafish tooth development. Supporting this idea, we found that morphological and gene expression evidence of tooth initiation is eliminated in shha mutant embryos, and that morpholino antisense oligonucleotide knockdown of shha, but not shhb, function prevents mature tooth formation. Hedgehog pathway inhibition with the antagonist compound cyclopamine affected tooth formation at each stage in which we applied it: arresting development at early stages and disrupting mature tooth morphology when applied later. These results suggest that hedgehog signaling is required continuously during odontogenesis. In contrast, over-expression of shha had no effect on the developing dentition, possibly because shha is normally extensively expressed in the zebrafish pharyngeal region. We have identified previously unknown requirements for hedgehog signaling for early tooth initiation and later morphogenesis. The similarity of our results with data from mouse and other vertebrates suggests that despite gene duplication and changes in the location of where teeth form, the roles of hedgehog signaling in tooth development have been largely conserved during evolution.

  4. Perineurial glia require Notch signaling during motor nerve development but not regeneration

    PubMed Central

    Binari, Laura A.; Lewis, Gwendolyn M.; Kucenas, Sarah

    2013-01-01

    Motor nerves play the critical role of shunting information out of the CNS to targets in the periphery. Their formation requires the coordinated development of distinct cellular components, including motor axons and the Schwann cells and perineurial glia that ensheath them. During nervous system assembly, these glial cells must migrate long distances and terminally differentiate, ensuring the efficient propagation of action potentials. Although we know quite a bit about the mechanisms that control Schwann cell development during this process, nothing is known about the mechanisms that mediate the migration and differentiation of perineurial glia. Using in vivo imaging in zebrafish, we demonstrate that Notch signaling is required for both perineurial migration and differentiation during nerve formation, but not regeneration. Interestingly, loss of Notch signaling in perineurial cells also causes a failure of Schwann cell differentiation, demonstrating that Schwann cells require perineurial glia for aspects of their own development. These studies describe a novel mechanism that mediates multiple aspects of perineurial development and reveal the critical importance of perineurial glia for Schwann cell maturation and nerve formation. PMID:23467342

  5. Gated auditory speech perception: effects of listening conditions and cognitive capacity.

    PubMed

    Moradi, Shahram; Lidestam, Björn; Saremi, Amin; Rönnberg, Jerker

    2014-01-01

    This study aimed to measure the initial portion of signal required for the correct identification of auditory speech stimuli (or isolation points, IPs) in silence and noise, and to investigate the relationships between auditory and cognitive functions in silence and noise. Twenty-one university students were presented with auditory stimuli in a gating paradigm for the identification of consonants, words, and final words in highly predictable and low predictable sentences. The Hearing in Noise Test (HINT), the reading span test, and the Paced Auditory Serial Attention Test were also administered to measure speech-in-noise ability, working memory and attentional capacities of the participants, respectively. The results showed that noise delayed the identification of consonants, words, and final words in highly predictable and low predictable sentences. HINT performance correlated with working memory and attentional capacities. In the noise condition, there were correlations between HINT performance, cognitive task performance, and the IPs of consonants and words. In the silent condition, there were no correlations between auditory and cognitive tasks. In conclusion, a combination of hearing-in-noise ability, working memory capacity, and attention capacity is needed for the early identification of consonants and words in noise.

  6. Gated auditory speech perception: effects of listening conditions and cognitive capacity

    PubMed Central

    Moradi, Shahram; Lidestam, Björn; Saremi, Amin; Rönnberg, Jerker

    2014-01-01

    This study aimed to measure the initial portion of signal required for the correct identification of auditory speech stimuli (or isolation points, IPs) in silence and noise, and to investigate the relationships between auditory and cognitive functions in silence and noise. Twenty-one university students were presented with auditory stimuli in a gating paradigm for the identification of consonants, words, and final words in highly predictable and low predictable sentences. The Hearing in Noise Test (HINT), the reading span test, and the Paced Auditory Serial Attention Test were also administered to measure speech-in-noise ability, working memory and attentional capacities of the participants, respectively. The results showed that noise delayed the identification of consonants, words, and final words in highly predictable and low predictable sentences. HINT performance correlated with working memory and attentional capacities. In the noise condition, there were correlations between HINT performance, cognitive task performance, and the IPs of consonants and words. In the silent condition, there were no correlations between auditory and cognitive tasks. In conclusion, a combination of hearing-in-noise ability, working memory capacity, and attention capacity is needed for the early identification of consonants and words in noise. PMID:24926274

  7. Attenuation of IL-7 receptor signaling is not required for allelic exclusion.

    PubMed

    Will, Wynette M; Aaker, Joshua D; Burchill, Matthew A; Harmon, Ian R; O'Neil, Jennifer J; Goetz, Christine A; Hippen, Keli L; Farrar, Michael A

    2006-03-15

    Allelic exclusion prevents pre-B cells from generating more than one functional H chain, thereby ensuring the formation of a unique pre-BCR. The signaling processes underlying allelic exclusion are not clearly understood. IL-7R-dependent signals have been clearly shown to regulate the accessibility of the Ig H chain locus. More recent work has suggested that pre-BCR-dependent attenuation of IL-7R signaling returns the H chain loci to an inaccessible state; this process has been proposed to underlie allelic exclusion. Importantly, this model predicts that preventing pre-BCR-dependent down-regulation of IL-7R signaling should interfere with allelic exclusion. To test this hypothesis, we made use of transgenic mice that express a constitutively active form of STAT5b (STAT5b-CA). STAT5b-CA expression restores V(D)J recombination in IL-7R(-/-) B cells, demonstrating that IL-7 regulates H chain locus accessibility and V(D)J recombination via STAT5 activation. To examine the effects of constitutively active STAT5b on allelic exclusion, we crossed STAT5b-CA mice (which express the IgM(b) allotype) to IgM(a) allotype congenic mice. We found no difference in the percentage of IgM(a)/IgM(b)-coexpressing B cells in STAT5b-CA vs littermate control mice; identical results were observed when crossing STAT5b-CA mice with hen egg lysozyme (HEL) H chain transgenic mice. The HEL transgene enforces allelic exclusion, preventing rearrangement of endogenous H chain genes; importantly, rearrangement of endogenous H chain genes was suppressed to a similar degree in STAT5b-CA vs HEL mice. Thus, attenuation of IL-7R/STAT5 signaling is not required for allelic exclusion.

  8. Auditory imagery: empirical findings.

    PubMed

    Hubbard, Timothy L

    2010-03-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d) auditory imagery's relationship to perception and memory (detection, encoding, recall, mnemonic properties, phonological loop), and (e) individual differences in auditory imagery (in vividness, musical ability and experience, synesthesia, musical hallucinosis, schizophrenia, amusia) are considered. It is concluded that auditory imagery (a) preserves many structural and temporal properties of auditory stimuli, (b) can facilitate auditory discrimination but interfere with auditory detection, (c) involves many of the same brain areas as auditory perception, (d) is often but not necessarily influenced by subvocalization, (e) involves semantically interpreted information and expectancies, (f) involves depictive components and descriptive components, (g) can function as a mnemonic but is distinct from rehearsal, and (h) is related to musical ability and experience (although the mechanisms of that relationship are not clear).

  9. Auditory target detection in reverberation

    NASA Astrophysics Data System (ADS)

    Zurek, Patrick M.; Freyman, Richard L.; Balakrishnan, Uma

    2004-04-01

    Measurements and theoretical predictions of auditory target detection in simulated reverberant conditions are reported. The target signals were pulsed 13-octave bands of noise and the masker signal was a continuous wideband noise. Target and masker signals were passed through a software simulation of a reverberant room with a rigid sphere modeling a listener's head. The location of the target was fixed while the location of the masker was varied in the simulated room. Degree of reverberation was controlled by varying the uniform acoustic absorption of the simulated room's surfaces. The resulting target and masker signals were presented to the listeners over headphones in monaural-left, monaural-right, or binaural listening modes. Changes in detection performance in the monaural listening modes were largely predictable from the changes in target-to-masker ratio in the target band, but with a few dB of extra masking in reverberation. Binaural detection performance was generally well predicted by applying Durlach's [in Foundations of Modern Auditory Theory (Academic, New York, 1972)] equalization-cancellation theory to the direct-plus-reverberant ear signals. Predictions in all cases were based on a statistical description of room acoustics and on acoustic diffraction by a sphere. The success of these detection models in the present well-controlled reverberant conditions suggests that they can be used to incorporate listening mode and source location as factors in speech-intelligibility predictions.

  10. Summary statistics in auditory perception.

    PubMed

    McDermott, Josh H; Schemitsch, Michael; Simoncelli, Eero P

    2013-04-01

    Sensory signals are transduced at high resolution, but their structure must be stored in a more compact format. Here we provide evidence that the auditory system summarizes the temporal details of sounds using time-averaged statistics. We measured discrimination of 'sound textures' that were characterized by particular statistical properties, as normally result from the superposition of many acoustic features in auditory scenes. When listeners discriminated examples of different textures, performance improved with excerpt duration. In contrast, when listeners discriminated different examples of the same texture, performance declined with duration, a paradoxical result given that the information available for discrimination grows with duration. These results indicate that once these sounds are of moderate length, the brain's representation is limited to time-averaged statistics, which, for different examples of the same texture, converge to the same values with increasing duration. Such statistical representations produce good categorical discrimination, but limit the ability to discern temporal detail.

  11. Mode-locking neurodynamics predict human auditory brainstem responses to musical intervals.

    PubMed

    Lerud, Karl D; Almonte, Felix V; Kim, Ji Chul; Large, Edward W

    2014-02-01

    The auditory nervous system is highly nonlinear. Some nonlinear responses arise through active processes in the cochlea, while others may arise in neural populations of the cochlear nucleus, inferior colliculus and higher auditory areas. In humans, auditory brainstem recordings reveal nonlinear population responses to combinations of pure tones, and to musical intervals composed of complex tones. Yet the biophysical origin of central auditory nonlinearities, their signal processing properties, and their relationship to auditory perception remain largely unknown. Both stimulus components and nonlinear resonances are well represented in auditory brainstem nuclei due to neural phase-locking. Recently mode-locking, a generalization of phase-locking that implies an intrinsically nonlinear processing of sound, has been observed in mammalian auditory brainstem nuclei. Here we show that a canonical model of mode-locked neural oscillation predicts the complex nonlinear population responses to musical intervals that have been observed in the human brainstem. The model makes predictions about auditory signal processing and perception that are different from traditional delay-based models, and may provide insight into the nature of auditory population responses. We anticipate that the application of dynamical systems analysis will provide the starting point for generic models of auditory population dynamics, and lead to a deeper understanding of nonlinear auditory signal processing possibly arising in excitatory-inhibitory networks of the central auditory nervous system. This approach has the potential to link neural dynamics with the perception of pitch, music, and speech, and lead to dynamical models of auditory system development.

  12. Cell-Specific Activity-Dependent Fractionation of Layer 2/3→5B Excitatory Signaling in Mouse Auditory Cortex

    PubMed Central

    Joshi, Ankur; Middleton, Jason W.; Anderson, Charles T.; Borges, Katharine; Suter, Benjamin A.; Shepherd, Gordon M. G.

    2015-01-01

    Auditory cortex (AC) layer 5B (L5B) contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. Although it is known that these neuronal types have distinct roles in auditory processing and different response properties to sound, the synaptic and intrinsic mechanisms shaping their input–output functions remain less understood. Here, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B. Corticocollicular neurons had, on average, lower input resistance, greater hyperpolarization-activated current (Ih), depolarized resting membrane potential, faster action potentials, initial spike doublets, and less spike-frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, the probabilities of connection, amplitude, latency, rise time, and decay time constant of the unitary EPSC were not different for L2/3→corticocollicular and L2/3→corticocallosal connections. However, short trains of unitary EPSCs showed no synaptic depression in L2/3→corticocollicular connections, but substantial depression in L2/3→corticocallosal connections. Synaptic potentials in L2/3→corticocollicular connections decayed faster and showed less temporal summation, consistent with increased Ih in corticocollicular neurons, whereas synaptic potentials in L2/3→corticocallosal connections showed more temporal summation. Extracellular L2/3 stimulation at two different rates resulted in spiking in L5B neurons; for corticocallosal neurons the spike rate was frequency dependent, but for corticocollicular neurons it was not. Together, these findings identify cell-specific intrinsic and synaptic mechanisms that divide intracortical synaptic excitation from L2/3 to L5B into two functionally distinct pathways with different input–output functions

  13. Auditory Temporal Processing Deficits in Children with Reading Disabilities

    ERIC Educational Resources Information Center

    Cohen-Mimran, Ravit; Sapir, Shimon

    2007-01-01

    The role of central auditory processing in reading skill development and reading disorders is unclear. The purpose of this study was to examine whether individuals with specific reading disabilities (SRD) have deficits in processing rapidly presented, serially ordered non-speech auditory signals. To this end, we compared 12 children with SRD and…

  14. Auditory Temporal Processing Deficits in Children with Reading Disabilities

    ERIC Educational Resources Information Center

    Cohen-Mimran, Ravit; Sapir, Shimon

    2007-01-01

    The role of central auditory processing in reading skill development and reading disorders is unclear. The purpose of this study was to examine whether individuals with specific reading disabilities (SRD) have deficits in processing rapidly presented, serially ordered non-speech auditory signals. To this end, we compared 12 children with SRD and…

  15. Neural dynamics of attending and ignoring in human auditory cortex.

    PubMed

    Chait, Maria; de Cheveigné, Alain; Poeppel, David; Simon, Jonathan Z

    2010-09-01

    Studies in all sensory modalities have demonstrated amplification of early brain responses to attended signals, but less is known about the processes by which listeners selectively ignore stimuli. Here we use MEG and a new paradigm to dissociate the effects of selectively attending, and ignoring in time. Two different tasks were performed successively on the same acoustic stimuli: triplets of tones (A, B, C) with noise-bursts interspersed between the triplets. In the COMPARE task subjects were instructed to respond when tones A and C were of same frequency. In the PASSIVE task they were instructed to respond as fast as possible to noise-bursts. COMPARE requires attending to A and C and actively ignoring tone B, but PASSIVE involves neither attending to nor ignoring the tones. The data were analyzed separately for frontal and auditory-cortical channels to independently address attentional effects on low-level sensory versus putative control processing. We observe the earliest attend/ignore effects as early as 100 ms post-stimulus onset in auditory cortex. These appear to be generated by modulation of exogenous (stimulus-driven) sensory evoked activity. Specifically related to ignoring, we demonstrate that active-ignoring-induced input inhibition involves early selection. We identified a sequence of early (<200 ms post-onset) auditory cortical effects, comprised of onset response attenuation and the emergence of an inhibitory response, and provide new, direct evidence that listeners actively ignoring a sound can reduce their stimulus related activity in auditory cortex by 100 ms after onset when this is required to execute specific behavioral objectives.

  16. Feature Assignment in Perception of Auditory Figure

    PubMed Central

    Gregg, Melissa K.; Samuel, Arthur G.

    2012-01-01

    Because the environment often includes multiple sounds that overlap in time, listeners must segregate a sound of interest (the auditory figure) from other co-occurring sounds (the unattended auditory ground). We conducted a series of experiments to clarify the principles governing the extraction of auditory figures. We distinguish between auditory “objects” (relatively punctate events, such as a dog's bark) and auditory “streams” (sounds involving a pattern over time, such as a galloping rhythm). In Experiments 1 and 2, on each trial two sounds -- an object (a vowel) and a stream (a series of tones) – were presented with one target feature that could be perceptually grouped with either source. In each block of these experiments, listeners were required to attend to one of the two sounds, and report its perceived category. Across several experimental manipulations, listeners were more likely to allocate the feature to an impoverished object if the result of the grouping was a good, identifiable object. Perception of objects was quite sensitive to feature variation (noise masking), whereas perception of streams was more robust to feature variation. In Experiment 3, the number of sound sources competing for the feature was increased to three. This produced a shift toward relying more on spatial cues than on the potential contribution of the feature to an object's perceptual quality. The results support a distinction between auditory objects and streams, and provide new information about the way that the auditory world is parsed. PMID:22288691

  17. PB1 Domain-Dependent Signaling Complex Is Required for Extracellular Signal-Regulated Kinase 5 Activation

    PubMed Central

    Nakamura, Kazuhiro; Uhlik, Mark T.; Johnson, Nancy L.; Hahn, Klaus M.; Johnson, Gary L.

    2006-01-01

    MEKK2, MEK5, and extracellular signal-regulated kinase 5 (ERK5) are members of a three-kinase cascade for the activation of ERK5. MEK5 is the only MAP2K to express a PB1 domain, and we have shown that it heterodimerizes with the PB1 domain of MEKK2. Here we demonstrate the MEK5 PB1 domain is a scaffold that also binds ERK5, functionally forming a MEKK2-MEK5-ERK5 complex. Reconstitution assays and CFP/YFP imaging (fluorescence resonance energy transfer [FRET]) measuring YFP-MEKK2/CFP-MEK5 and CFP-MEK5/YFP-ERK5 interactions define distinct MEK5 PB1 domain binding sites for MEKK2 and ERK5, with a C-terminal extension of the PB1 domain contributing to ERK5 binding. Stimulus-dependent CFP/YFP FRET in combination with mutational analysis was used to define MEK5 PB1 domain residues critical for the interaction of MEKK2/MEK5 and MEK5/ERK5 required for activation of the ERK5 pathway in living cells. Fusion of the MEK5 PB1 domain to the N terminus of MEK1 confers ERK5 regulation by a MAP2K normally regulating only ERK1/2. The MEK5 PB1 domain confers stringent MAP3K regulation of ERK5 relative to more promiscuous MAP3K control of ERK1/2, JNK, and p38. PMID:16507987

  18. Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex.

    PubMed

    Lui, Jan H; Nowakowski, Tomasz J; Pollen, Alex A; Javaherian, Ashkan; Kriegstein, Arnold R; Oldham, Michael C

    2014-11-13

    Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche during neocortical development. Such adaptations may have evolved through gene expression changes in RG. However, whether or how RG gene expression varies between humans and other species is unknown. Here we show that the transcriptional profiles of human and mouse neocortical RG are broadly conserved during neurogenesis, yet diverge for specific signalling pathways. By analysing differential gene co-expression relationships between the species, we demonstrate that the growth factor PDGFD is specifically expressed by RG in human, but not mouse, corticogenesis. We also show that the expression domain of PDGFRβ, the cognate receptor for PDGFD, is evolutionarily divergent, with high expression in the germinal region of dorsal human neocortex but not in the mouse. Pharmacological inhibition of PDGFD-PDGFRβ signalling in slice culture prevents normal cell cycle progression of neocortical RG in human, but not mouse. Conversely, injection of recombinant PDGFD or ectopic expression of constitutively active PDGFRβ in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD-PDGFRβ signalling for human neocortical development and suggest that local production of growth factors by RG supports the expanded germinal region and progenitor heterogeneity of species with large brains.

  19. Lhx9 gene expression during early limb development in mice requires the FGF signalling pathway.

    PubMed

    Yang, Yisheng; Wilson, Megan J

    2015-01-01

    Lhx9 is a member of the LIM-homeodomain gene family necessary for the correct development of many organs including gonads, limbs, heart and the nervous system. In the context of limb development, Lhx9 has been implicated as an integrator for Fibroblast growth factor (FGF) and Sonic hedgehog (Shh) signalling required for proximal-distal (PD) and anterior-posterior (AP) development of the limb. Three splice variants of the Lhx9 transcript are expressed during development, two of which are predicted to act in a dominant negative fashion, competing with the DNA binding version of Lhx9 for binding to cofactors via the LIM-domain. We examined the expression pattern for the three alternative splice forms of Lhx9; Lhx9α, Lhx9β and Lhx9c during early limb development. We have found that of the three Lhx9 isoforms, only Lhx9α and Lhx9c (intact homeodomain) are expressed during early limb development, each with their own distinct expression pattern. Additionally we determined that Lhx9 expression overlaps with FGF10 expression in the developing limb bud mesenchyme. Limb bud explant cultures, in the presence of signalling pathway inhibitors, also indicated that Lhx9 mRNA expression in the limb bud was dependent on FGF signalling.

  20. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses.

    PubMed

    Zhang, Rong; Miner, Jonathan J; Gorman, Matthew J; Rausch, Keiko; Ramage, Holly; White, James P; Zuiani, Adam; Zhang, Ping; Fernandez, Estefania; Zhang, Qiang; Dowd, Kimberly A; Pierson, Theodore C; Cherry, Sara; Diamond, Michael S

    2016-07-07

    Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available. We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, Dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with unknown host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern.

  1. Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation.

    PubMed

    Wang, Xi-De; Leow, Ching Ching; Zha, Jiping; Tang, Zhijun; Modrusan, Zora; Radtke, Freddy; Aguet, Michel; de Sauvage, Frederic J; Gao, Wei-Qiang

    2006-02-01

    Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. Using a transgenic cell ablation approach, we found in our previous study that cells expressing Notch1 are crucial for prostate early development and re-growth. Here, we further define the role of Notch signaling in regulating prostatic epithelial cell growth and differentiation using biochemical and genetic approaches in ex vivo or in vivo systems. Treatment of developing prostate grown in culture with inhibitors of gamma-secretase/presenilin, which is required for Notch cleavage and activation, caused a robust increase in proliferation of epithelial cells co-expressing cytokeratin 8 and 14, lack of luminal/basal layer segregation and dramatically reduced branching morphogenesis. Using conditional Notch1 gene deletion mouse models, we found that inactivation of Notch1 signaling resulted in profound prostatic alterations, including increased tufting, bridging and enhanced epithelial proliferation. Cells within these lesions co-expressed both luminal and basal cell markers, a feature of prostatic epithelial cells in predifferentiation developmental stages. Microarray analysis revealed that the gene expression in a number of genetic networks was altered following Notch1 gene deletion in prostate. Furthermore, expression of Notch1 and its effector Hey-1 gene in human prostate adenocarcinomas were found significantly down-regulated compared to normal control tissues. Taken together, these data suggest that Notch signaling is critical for normal cell proliferation and differentiation in the prostate, and deregulation of this pathway may facilitate prostatic tumorigenesis.

  2. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses

    PubMed Central

    Zhang, Rong; Miner, Jonathan J.; Gorman, Matthew J.; Rausch, Keiko; Ramage, Holly; White, James P.; Zuiani, Adam; Zhang, Ping; Fernandez, Estefania; Zhang, Qiang; Dowd, Kimberly A.; Pierson, Theodore C.; Cherry, Sara; Diamond, Michael S.

    2016-01-01

    Flaviviruses infect hundreds of millions of people annually, with no antiviral therapy available1,2. We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that when edited resulted in reduced flavivirus infection. We validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum (ER) functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of ER-associated signal peptidase complex (SPCS) proteins was necessary for the proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, Dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), yet had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I MHC antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with unknown host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection of the expanding number of flaviviruses of medical concern. PMID:27383988

  3. Dynamin II is required for 17β-estradiol signaling and autophagy-based ERα degradation

    PubMed Central

    Totta, Pierangela; Busonero, Claudia; Leone, Stefano; Marino, Maria; Acconcia, Filippo

    2016-01-01

    17β-estradiol (E2) regulates diverse physiological effects, including cell proliferation, by binding to estrogen receptor α (ERα). ERα is both a transcription factor that drives E2-sensitive gene expression and an extra-nuclear localized receptor that triggers the activation of diverse kinase cascades. While E2 triggers cell proliferation, it also induces ERα degradation in a typical hormone-dependent feedback loop. Although ERα breakdown proceeds through the 26S proteasome, a role for lysosomes and for some endocytic proteins in controlling ERα degradation has been reported. Here, we studied the role of the endocytic protein dynamin II in E2-dependent ERα signaling and degradation. The results indicate that dynamin II siRNA-mediated knock-down partially prevents E2-induced ERα degradation through the inhibition of an autophagy-based pathway and impairs E2-induced cell proliferation signaling. Altogether, these data demonstrate that dynamin II is required for the E2:ERα signaling of physiological functions and uncovers a role for autophagy in the control of ERα turnover. PMID:27009360

  4. Autophagy-associated alpha-arrestin signaling is required for conidiogenous cell development in Magnaporthe oryzae

    PubMed Central

    Dong, Bo; Xu, Xiaojin; Chen, Guoqing; Zhang, Dandan; Tang, Mingzhi; Xu, Fei; Liu, Xiaohong; Wang, Hua; Zhou, Bo

    2016-01-01

    Conidiation patterning is evolutionarily complex and mechanism concerning conidiogenous cell differentiation remains largely unknown. Magnaporthe oryzae conidiates in a sympodial way and uses its conidia to infect host and disseminate blast disease. Arrestins are multifunctional proteins that modulate receptor down-regulation and scaffold components of intracellular trafficking routes. We here report an alpha-arrestin that regulates patterns of conidiation and contributes to pathogenicity in M. oryzae. We show that disruption of ARRDC1 generates mutants which produce conidia in an acropetal array and ARRDC1 significantly affects expression profile of CCA1, a virulence-related transcription factor required for conidiogenous cell differentiation. Although germ tubes normally develop appressoria, penetration peg formation is dramatically impaired and Δarrdc1 mutants are mostly nonpathogenic. Fluorescent analysis indicates that EGFP-ARRDC1 puncta are well colocalized with DsRed2-Atg8, and this distribution profile could not be altered in Δatg9 mutants, suggesting ARRDC1 enters into autophagic flux before autophagosome maturation. We propose that M. oryzae employs ARRDC1 to regulate specific receptors in response to conidiation-related signals for conidiogenous cell differentiation and utilize autophagosomes for desensitization of conidiogenous receptor, which transmits extracellular signal to the downstream elements of transcription factors. Our investigation extends novel significance of autophagy-associated alpha-arrestin signaling to fungal parasites. PMID:27498554

  5. Intracellular Ca(2+) signaling is required for neurotrophin-induced potentiation in the adult rat hippocampus.

    PubMed

    Kang, H; Schuman, E M

    2000-03-24

    Recent studies have demonstrated the importance of neurotrophin function in adult synaptic plasticity. In an effort to characterize the intracellular signaling pathways that couple Trk receptor activation to the final physiological effects of neurotrophins, we have examined the role of intracellular calcium rises in neurotrophin-induced synaptic enhancement in hippocampal slices. Using pharmacological blockers to two different calcium ion (Ca(2+)) sources, voltage-gated Ca(2+) channels and intracellular Ca(2+) stores, we show that the potentiating effects of neurotrophins in hippocampal slices are mediated by intracellular Ca(2+) signaling. Although basal synaptic transmission between hippocampal CA3 and CA1 neurons was not affected by nifedipine or thapsigargin, both drugs significantly attenuated brain-derived neurotrophic factor or neurotrophin-3-induced synaptic enhancement. The pharmacological blockade of Ca(2+) signaling is effective only during the initial period of neurotrophin-induced potentiation. These data suggest that the minimal requirements for inducing potentiation by neurotrophins involve a transient increase in intracellular Ca(2+) concentration, via voltage-gated Ca(2+) channels and/or intracellular Ca(2+) stores.

  6. Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis.

    PubMed

    Xu, Keli; Nieuwenhuis, Erica; Cohen, Brenda L; Wang, Wei; Canty, Angelo J; Danska, Jayne S; Coultas, Leigh; Rossant, Janet; Wu, Megan Y J; Piscione, Tino D; Nagy, Andras; Gossler, Achim; Hicks, Geoff G; Hui, Chi-Chung; Henkelman, R Mark; Yu, Lisa X; Sled, John G; Gridley, Thomas; Egan, Sean E

    2010-01-01

    Distal lung development occurs through coordinated induction of myofibroblasts, epithelial cells, and capillaries. Lunatic Fringe (Lfng) is a beta(1-3) N-acetylglucosamine transferase that modifies Notch receptors to facilitate their activation by Delta-like (Dll1/4) ligands. Lfng is expressed in the distal lung during saccular development, and deletion of this gene impairs myofibroblast differentiation and alveogenesis in this context. A similar defect was observed in Notch2(beta-geo/+)Notch3(beta-geo/beta-geo) compound mutant mice but not in Notch2(beta-geo/+) or Notch3(beta-geo/beta-geo) single mutants. Finally, to directly test for the role of Notch signaling in myofibroblast differentiation in vivo, we used ROSA26-rtTA(/+);tetO-CRE(/+);RBPJkappa(flox/flox) inducible mutant mice to show that disruption of canonical Notch signaling during late embryonic development prevents induction of smooth muscle actin in mesenchymal cells of the distal lung. In sum, these results demonstrate that Lfng functions to enhance Notch signaling in myofibroblast precursor cells and thereby to coordinate differentiation and mobilization of myofibroblasts required for alveolar septation.

  7. Cytoplasmic nanojunctions between lysosomes and sarcoplasmic reticulum are required for specific calcium signaling

    PubMed Central

    Fameli, Nicola; Ogunbayo, Oluseye A.

    2014-01-01

    Herein we demonstrate how nanojunctions between lysosomes and sarcoplasmic reticulum (L-SR junctions) serve to couple lysosomal activation to regenerative, ryanodine receptor-mediated cellular Ca 2+ waves. In pulmonary artery smooth muscle cells (PASMCs) it has been proposed that nicotinic acid adenine dinucleotide phosphate (NAADP) triggers increases in cytoplasmic Ca 2+ via L-SR junctions, in a manner that requires initial Ca 2+ release from lysosomes and subsequent Ca 2+-induced Ca 2+ release (CICR) via ryanodine receptor (RyR) subtype 3 on the SR membrane proximal to lysosomes. L-SR junction membrane separation has been estimated to be < 400 nm and thus beyond the resolution of light microscopy, which has restricted detailed investigations of the junctional coupling process. The present study utilizes standard and tomographic transmission electron microscopy to provide a thorough ultrastructural characterization of the L-SR junctions in PASMCs. We show that L-SR nanojunctions are prominent features within these cells and estimate that the junctional membrane separation and extension are about 15 nm and 300 nm, respectively. Furthermore, we develop a quantitative model of the L-SR junction using these measurements, prior kinetic and specific Ca 2+ signal information as input data. Simulations of NAADP-dependent junctional Ca 2+ transients demonstrate that the magnitude of these signals can breach the threshold for CICR via RyR3. By correlation analysis of live cell Ca 2+ signals and simulated Ca 2+ transients within L-SR junctions, we estimate that “trigger zones” comprising 60–100 junctions are required to confer a signal of similar magnitude. This is compatible with the 110 lysosomes/cell estimated from our ultrastructural observations. Most importantly, our model shows that increasing the L-SR junctional width above 50 nm lowers the magnitude of junctional [Ca 2+] such that there is a failure to breach the threshold for CICR via RyR3. L-SR junctions are

  8. Auditory Distraction and Acclimatization to Hearing Aids.

    PubMed

    Dawes, Piers; Munro, Kevin J

    It is widely recognized by hearing aid users and audiologists that a period of auditory acclimatization and adjustment is needed for new users to become accustomed to their devices. The aim of the present study was to test the idea that auditory acclimatization and adjustment to hearing aids involves a process of learning to "tune out" newly audible but undesirable sounds, which are described by new hearing aid users as annoying and distracting. It was hypothesized that (1) speech recognition thresholds in noise would improve over time for new hearing aid users, (2) distractibility to noise would reduce over time for new hearing aid users, (3) there would be a correlation between improved speech recognition in noise and reduced distractibility to background sounds, (4) improvements in speech recognition and distraction would be accompanied by self-report of reduced annoyance, and (5) improvements in speech recognition and distraction would be associated with higher general cognitive ability and more hearing aid use. New adult hearing aid users (n = 35) completed a test of aided speech recognition in noise (SIN) and a test of auditory distraction by background sound amplified by hearing aids on the day of fitting and 1, 7, 14, and 30 days post fitting. At day 30, participants completed self-ratings of the annoyance of amplified sounds. Daily hearing aid use was measured via hearing aid data logging, and cognitive ability was measured with the Wechsler Abbreviated Scale of Intelligence block design test. A control group of experienced hearing aid users (n = 20) completed the tests over a similar time frame. At day 30, there was no statistically significant improvement in SIN among new users versus experienced users. However, levels of hearing loss and hearing aid use varied widely among new users. A subset of new users with moderate hearing loss who wore their hearing aids at least 6 hr/day (n = 10) had significantly improved SIN (by ~3-dB signal to noise ratio

  9. Insulin signaling is acutely required for long-term memory in Drosophila.

    PubMed

    Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V

    2015-01-01

    Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.

  10. Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation

    PubMed Central

    Phee, Hyewon; Au-Yeung, Byron B; Pryshchep, Olga; O'Hagan, Kyle Leonard; Fairbairn, Stephanie Grace; Radu, Maria; Kosoff, Rachelle; Mollenauer, Marianne; Cheng, Debra; Chernoff, Jonathan; Weiss, Arthur

    2014-01-01

    The molecular mechanisms that govern thymocyte development and maturation are incompletely understood. The P21-activated kinase 2 (Pak2) is an effector for the Rho family GTPases Rac and Cdc42 that regulate actin cytoskeletal remodeling, but its role in the immune system remains poorly understood. In this study, we show that T-cell specific deletion of Pak2 gene in mice resulted in severe T cell lymphopenia accompanied by marked defects in development, maturation, and egress of thymocytes. Pak2 was required for pre-TCR β-selection and positive selection. Surprisingly, Pak2 deficiency in CD4 single positive thymocytes prevented functional maturation and reduced expression of S1P1 and KLF2. Mechanistically, Pak2 is required for actin cytoskeletal remodeling triggered by TCR. Failure to induce proper actin cytoskeletal remodeling impaired PLCγ1 and Erk1/2 signaling in the absence of Pak2, uncovering the critical function of Pak2 as an essential regulator that governs the actin cytoskeleton-dependent signaling to ensure normal thymocyte development and maturation. DOI: http://dx.doi.org/10.7554/eLife.02270.001 PMID:24843022

  11. JNK signaling in insulin-producing cells is required for adaptive responses to stress in Drosophila

    PubMed Central

    Karpac, Jason; Hull-Thompson, Julie; Falleur, Melody; Jasper, Heinrich

    2009-01-01

    Summary Adaptation to environmental challenges is critical for survival of an organism. Repression of Insulin/IGF Signaling (IIS) by stress-responsive Jun-N-terminal Kinase (JNK) signaling is emerging as a conserved mechanism that allows reallocating resources from anabolic to repair processes under stress conditions. JNK activation in Insulin producing cells (IPCs) is sufficient to repress Insulin and Insulin-like peptide (ILP) expression in rats and flies, but the significance of this interaction for adaptive responses to stress is unclear. Here we show that JNK activity in IPCs of flies is required for oxidative stress-induced repression of the Drosophila ILP2. We find that this repression is required for growth adaptation to heat stress as well as adult oxidative stress tolerance, and that induction of stress response genes in the periphery is in part dependent on IPC-specific JNK activity. Endocrine control of IIS by JNK in IPCs is thus critical for systemic adaptation to stress. PMID:19627268

  12. Insulin signaling is acutely required for long-term memory in Drosophila

    PubMed Central

    Chambers, Daniel B.; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V.

    2015-01-01

    Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies. PMID:25805973

  13. Effects of an Auditory Lateralization Training in Children Suspected to Central Auditory Processing Disorder

    PubMed Central

    Lotfi, Yones; Moosavi, Abdollah; Bakhshi, Enayatollah; Sadjedi, Hamed

    2016-01-01

    Background and Objectives Central auditory processing disorder [(C)APD] refers to a deficit in auditory stimuli processing in nervous system that is not due to higher-order language or cognitive factors. One of the problems in children with (C)APD is spatial difficulties which have been overlooked despite their significance. Localization is an auditory ability to detect sound sources in space and can help to differentiate between the desired speech from other simultaneous sound sources. Aim of this research was investigating effects of an auditory lateralization training on speech perception in presence of noise/competing signals in children suspected to (C)APD. Subjects and Methods In this analytical interventional study, 60 children suspected to (C)APD were selected based on multiple auditory processing assessment subtests. They were randomly divided into two groups: control (mean age 9.07) and training groups (mean age 9.00). Training program consisted of detection and pointing to sound sources delivered with interaural time differences under headphones for 12 formal sessions (6 weeks). Spatial word recognition score (WRS) and monaural selective auditory attention test (mSAAT) were used to follow the auditory lateralization training effects. Results This study showed that in the training group, mSAAT score and spatial WRS in noise (p value≤0.001) improved significantly after the auditory lateralization training. Conclusions We used auditory lateralization training for 6 weeks and showed that auditory lateralization can improve speech understanding in noise significantly. The generalization of this results needs further researches. PMID:27626084

  14. The Contribution of Brainstem and Cerebellar Pathways to Auditory Recognition

    PubMed Central

    McLachlan, Neil M.; Wilson, Sarah J.

    2017-01-01

    The cerebellum has been known to play an important role in motor functions for many years. More recently its role has been expanded to include a range of cognitive and sensory-motor processes, and substantial neuroimaging and clinical evidence now points to cerebellar involvement in most auditory processing tasks. In particular, an increase in the size of the cerebellum over recent human evolution has been attributed in part to the development of speech. Despite this, the auditory cognition literature has largely overlooked afferent auditory connections to the cerebellum that have been implicated in acoustically conditioned reflexes in animals, and could subserve speech and other auditory processing in humans. This review expands our understanding of auditory processing by incorporating cerebellar pathways into the anatomy and functions of the human auditory system. We reason that plasticity in the cerebellar pathways underpins implicit learning of spectrotemporal information necessary for sound and speech recognition. Once learnt, this information automatically recognizes incoming auditory signals and predicts likely subsequent information based on previous experience. Since sound recognition processes involving the brainstem and cerebellum initiate early in auditory processing, learnt information stored in cerebellar memory templates could then support a range of auditory processing functions such as streaming, habituation, the integration of auditory feature information such as pitch, and the recognition of vocal communications. PMID:28373850

  15. The Contribution of Brainstem and Cerebellar Pathways to Auditory Recognition.

    PubMed

    McLachlan, Neil M; Wilson, Sarah J

    2017-01-01

    The cerebellum has been known to play an important role in motor functions for many years. More recently its role has been expanded to include a range of cognitive and sensory-motor processes, and substantial neuroimaging and clinical evidence now points to cerebellar involvement in most auditory processing tasks. In particular, an increase in the size of the cerebellum over recent human evolution has been attributed in part to the development of speech. Despite this, the auditory cognition literature has largely overlooked afferent auditory connections to the cerebellum that have been implicated in acoustically conditioned reflexes in animals, and could subserve speech and other auditory processing in humans. This review expands our understanding of auditory processing by incorporating cerebellar pathways into the anatomy and functions of the human auditory system. We reason that plasticity in the cerebellar pathways underpins implicit learning of spectrotemporal information necessary for sound and speech recognition. Once learnt, this information automatically recognizes incoming auditory signals and predicts likely subsequent information based on previous experience. Since sound recognition processes involving the brainstem and cerebellum initiate early in auditory processing, learnt information stored in cerebellar memory templates could then support a range of auditory processing functions such as streaming, habituation, the integration of auditory feature information such as pitch, and the recognition of vocal communications.

  16. Absence of both auditory evoked potentials and auditory percepts dependent on timing cues.

    PubMed

    Starr, A; McPherson, D; Patterson, J; Don, M; Luxford, W; Shannon, R; Sininger, Y; Tonakawa, L; Waring, M

    1991-06-01

    An 11-yr-old girl had an absence of sensory components of auditory evoked potentials (brainstem, middle and long-latency) to click and tone burst stimuli that she could clearly hear. Psychoacoustic tests revealed a marked impairment of those auditory perceptions dependent on temporal cues, that is, lateralization of binaural clicks, change of binaural masked threshold with changes in signal phase, binaural beats, detection of paired monaural clicks, monaural detection of a silent gap in a sound, and monaural threshold elevation for short duration tones. In contrast, auditory functions reflecting intensity or frequency discriminations (difference limens) were only minimally impaired. Pure tone audiometry showed a moderate (50 dB) bilateral hearing loss with a disproportionate severe loss of word intelligibility. Those auditory evoked potentials that were preserved included (1) cochlear microphonics reflecting hair cell activity; (2) cortical sustained potentials reflecting processing of slowly changing signals; and (3) long-latency cognitive components (P300, processing negativity) reflecting endogenous auditory cognitive processes. Both the evoked potential and perceptual deficits are attributed to changes in temporal encoding of acoustic signals perhaps occurring at the synapse between hair cell and eighth nerve dendrites. The results from this patient are discussed in relation to previously published cases with absent auditory evoked potentials and preserved hearing.

  17. Epidermal hyperplasia induced by Raf-MAPK signaling requires Stat3 activation.

    PubMed

    Tarutani, Masahito; Nakajima, Kimiko; Takaishi, Mikiro; Ohko, Kentaro; Sano, Shigetoshi

    2013-11-01

    Raf is one of the downstream effectors of Ras GTPases, and plays a key role in regulating cell proliferation and differentiation through the activation of MAPK. We have previously demonstrated that temporal induction of Raf in the epidermis of K14-Raf:ER transgenic mice results in epidermal hyperplasia resembling squamous cell carcinoma and psoriasis. It has been demonstrated that epidermal Stat3 activation is required for psoriasis development, since keratinocyte-specific Stat3 activation in a mouse model elicits a psoriasis-like phenotype, which is reversed by inhibition of Stat3 signaling. The aim of this study was whether Stat3 signaling is involved in Raf-MAPK-dependent epidermal hyperplasia. K14-Raf:ER transgenic mice, in which the 4-hydroxytamoxifen (4OHT)-responsive mutant estrogen receptor ligand binding domain-Raf fusion gene is expressed under control of the keratin 14 promoter, were mated with epidermis-specific Stat3 null mice (K5-Cre.Stat3(flox/flox)). K5-Cre.Stat3(flox/flox) mice were used to define the impact of Stat3 deficiency on Raf-induced epidermal hyperplasia. Over-expression of Raf by 4OHT treatment in K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice greatly attenuated the epidermal hyperplasia and dermal cell infiltrates compared with K14-Raf:ER;K5-Cre.Stat3(flox/WT) mice. Also, up-regulation of psoriasis-associated cytokine profiles, including VEGF, was inhibited in the skin from K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice following 4OHT treatment. These results clearly indicate that Raf-MAPK-dependent psoriatic-like epidermal hyperplasia requires Stat3 signaling in keratinocytes. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Syd/JIP3 and JNK Signaling Are Required for Myonuclear Positioning and Muscle Function

    PubMed Central

    Schulman, Victoria K.; Folker, Eric S.; Rosen, Jonathan N.; Baylies, Mary K.

    2014-01-01

    Highlighting the importance of proper intracellular organization, many muscle diseases are characterized by mispositioned myonuclei. Proper positioning of myonuclei is dependent upon the microtubule motor proteins, Kinesin-1 and cytoplasmic Dynein, and there are at least two distinct mechanisms by which Kinesin and Dynein move myonuclei. The motors exert forces both directly on the nuclear surface and from the cell cortex via microtubules. How these activities are spatially segregated yet coordinated to position myonuclei is unknown. Using Drosophila melanogaster, we identified that Sunday Driver (Syd), a homolog of mammalian JNK-interacting protein 3 (JIP3), specifically regulates Kinesin- and Dynein-dependent cortical pulling of myonuclei without affecting motor activity near the nucleus. Specifically, Syd mediates Kinesin-dependent localization of Dynein to the muscle ends, where cortically anchored Dynein then pulls microtubules and the attached myonuclei into place. Proper localization of Dynein also requires activation of the JNK signaling cascade. Furthermore, Syd functions downstream of JNK signaling because without Syd, JNK signaling is insufficient to promote Kinesin-dependent localization of Dynein to the muscle ends. The significance of Syd-dependent myonuclear positioning is illustrated by muscle-specific depletion of Syd, which impairs muscle function. Moreover, both myonuclear spacing and locomotive defects in syd mutants can be rescued by expression of mammalian JIP3 in Drosophila muscle tissue, indicating an evolutionarily conserved role for JIP3 in myonuclear movement and highlighting the utility of Drosophila as a model for studying mammalian development. Collectively, we implicate Syd/JIP3 as a novel regulator of myogenesis that is required for proper intracellular organization and tissue function. PMID:25522254

  19. Calcium influx-mediated signaling is required for complete mouse egg activation.

    PubMed

    Miao, Yi-Liang; Stein, Paula; Jefferson, Wendy N; Padilla-Banks, Elizabeth; Williams, Carmen J

    2012-03-13

    Mammalian fertilization is accompanied by oscillations in egg cytoplasmic calcium (Ca(2+)) concentrations that are critical for completion of egg activation. These oscillations are initiated by Ca(2+) release from inositol 1,4,5-trisphosphate (IP(3))-sensitive intracellular stores. We tested the hypothesis that Ca(2+) influx across the plasma membrane was a requisite component of egg activation signaling, and not simply a Ca(2+) source for store repletion. Using intracytoplasmic sperm injection (ICSI) and standard in vitro fertilization (IVF), we found that Ca(2+) influx was not required to initiate resumption of meiosis II. However, even if multiple oscillations in intracellular Ca(2+) occurred, in the absence of Ca(2+) influx, the fertilized eggs failed to emit the second polar body, resulting in formation of three pronuclei. Additional experiments using the Ca(2+) chelator, BAPTA/AM, demonstrated that Ca(2+) influx is sufficient to support polar body emission and pronucleus formation after only a single sperm-induced Ca(2+) transient, whereas BAPTA/AM-treated ICSI or fertilized eggs cultured in Ca(2+)-free medium remained arrested in metaphase II. Inhibition of store-operated Ca(2+) entry had no effect on ICSI-induced egg activation, so Ca(2+) influx through alternative channels must participate in egg activation signaling. Ca(2+) influx appears to be upstream of CaMKIIγ activity because eggs can be parthenogenetically activated with a constitutively active form of CaMKIIγ in the absence of extracellular Ca(2+). These results suggest that Ca(2+) influx at fertilization not only maintains Ca(2+) oscillations by replenishing Ca(2+) stores, but also activates critical signaling pathways upstream of CaMKIIγ that are required for second polar body emission.

  20. Gpr177-mediated Wnt Signaling is Required for Fungiform Placode Initiation.

    PubMed

    Zhu, X; Liu, Y; Zhao, P; Dai, Z; Yang, X; Li, Y; Qiu, M; Zhang, Z

    2014-06-01

    Fungiform papillae are formed as patterned rows on the surface of the anterior tongue at early organogenesis and contain one taste bud in each papilla to form one of the important sensory organs. Despite the essential role of Wnt/β-catenin signaling in controlling the development of fungiform taste papillae, the universal function of Wnt ligands in the initiation of the fungiform placode has not been completely elucidated. Here, by Shh (Cre) -mediated oral epithelial deletion of Wntless (Gpr177), a regulator essential for intracellular Wnt trafficking, we demonstrate that an overall function of Wnts is required for initiation of the fungiform placode. Multiple Wnts are expressed in the tongue epithelium at E11.5 before initiation of the fungiform placodes. Epithelial Gpr177 loss-of-function, associated with reduction of canonical Wnt signaling in lingual epithelium as exhibited by a loss of TopGal activity and Axin2 expression, results in the failure of fungiform placode initiation, as assessed by diminished expression of several taste placode molecular markers. Moreover, LiCl treatment of Gpr177 epithelial-deficient tongue explants at E11.5, but not at E12.5, restores tongue placode formation, demonstrating that Wnt ligands in the tongue surface prior to but not after fungiform placode initiation are responsible for fungiform papilla initiation. Epithelium-specific expression of an active β-catenin in the Gpr177-deficient tongue leads to fungiform papillae generation, suggesting that an intra-epithelial response to Wnts is required for placode initiation. Together, these results suggest that Gpr177 controls epithelial initiation of the fungiform placode through signaling via epithelial Wnt ligands.

  1. Gpr177-mediated Wnt Signaling Is Required for Secondary Palate Development.

    PubMed

    Liu, Y; Wang, M; Zhao, W; Yuan, X; Yang, X; Li, Y; Qiu, M; Zhu, X-J; Zhang, Z

    2015-07-01

    Cleft palate represents one of the major congenital birth defects in humans. Despite the essential roles of ectodermal canonical Wnt and mesenchymal Wnt signaling in the secondary palate development, the function of mesenchymal canonical Wnt activity in secondary palate development remains elusive. Here we show that Gpr177, a highly conserved transmembrane protein essential for Wnt trafficking, is required for secondary palate development. Gpr177 is expressed in both epithelium and mesenchyme of palatal shelves during mouse development. Wnt1(Cre)-mediated deletion of Gpr177 in craniofacial neural crest cells leads to a complete cleft secondary palate, which is formed mainly due to aberrant cell proliferation and increased cell death in palatal shelves. By BATGAL staining, we reveal an intense canonical Wnt activity in the anterior palate mesenchyme of E12.5 wild-type embryos but not in Gpr177(Wnt1-Cre) embryos, suggesting that mesenchymal canonical Wnt signaling activated by Gpr177-mediated mesenchymal Wnts is critical for secondary palate development. Moreover, phosphorylation of JNK and c-Jun is impaired in the Gpr177(Wnt1-Cre) palate and is restored by implantation of Wnt5a-soaked beads in the in vitro palate explants, suggesting that Gpr177 probably regulates palate development via the Wnt5a-mediated noncanonical Wnt pathway in which c-Jun and JNK are involved. Importantly, certain cellular processes and the altered gene expression in palates lacking Gpr177 are distinct from that of the Wnt5a mutant, further demonstrating involvement of other mesenchymal Wnts in the process of palate development. Together, these results suggest that mesenchymal Gpr177 is required for secondary palate development by regulating and integrating mesenchymal canonical and noncanonical Wnt signals.

  2. Calcium influx-mediated signaling is required for complete mouse egg activation

    PubMed Central

    Miao, Yi-Liang; Stein, Paula; Jefferson, Wendy N.; Padilla-Banks, Elizabeth; Williams, Carmen J.

    2012-01-01

    Mammalian fertilization is accompanied by oscillations in egg cytoplasmic calcium (Ca2+) concentrations that are critical for completion of egg activation. These oscillations are initiated by Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular stores. We tested the hypothesis that Ca2+ influx across the plasma membrane was a requisite component of egg activation signaling, and not simply a Ca2+ source for store repletion. Using intracytoplasmic sperm injection (ICSI) and standard in vitro fertilization (IVF), we found that Ca2+ influx was not required to initiate resumption of meiosis II. However, even if multiple oscillations in intracellular Ca2+ occurred, in the absence of Ca2+ influx, the fertilized eggs failed to emit the second polar body, resulting in formation of three pronuclei. Additional experiments using the Ca2+ chelator, BAPTA/AM, demonstrated that Ca2+ influx is sufficient to support polar body emission and pronucleus formation after only a single sperm-induced Ca2+ transient, whereas BAPTA/AM-treated ICSI or fertilized eggs cultured in Ca2+-free medium remained arrested in metaphase II. Inhibition of store-operated Ca2+ entry had no effect on ICSI-induced egg activation, so Ca2+ influx through alternative channels must participate in egg activation signaling. Ca2+ influx appears to be upstream of CaMKIIγ activity because eggs can be parthenogenetically activated with a constitutively active form of CaMKIIγ in the absence of extracellular Ca2+. These results suggest that Ca2+ influx at fertilization not only maintains Ca2+ oscillations by replenishing Ca2+ stores, but also activates critical signaling pathways upstream of CaMKIIγ that are required for second polar body emission. PMID:22371584

  3. Hmga2 is required for canonical WNT signaling during lung development

    PubMed Central

    2014-01-01

    Background The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. HMG proteins are present at high levels in various undifferentiated tissues during embryonic development and their levels are strongly reduced in the corresponding adult tissues, where they have been implicated in maintaining and activating stem/progenitor cells. Here we deciphered the role of the high-mobility-group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2-deficient mice (Hmga2 −/− ). Results We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2 −/− mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA-binding protein 6 and frizzled homolog 2. Analysis of siRNA-mediated loss-of-function experiments in embryonic lung explant culture confirmed the role of Hmga2 as a key regulator of distal lung epithelium differentiation and supported the causal involvement of enhanced canonical WNT signaling in mediating the effect of Hmga2-loss-of-fuction. Finally, we found that HMGA2 directly regulates Gata6 and thereby modulates Fzd2 expression. Conclusions Our results support that Hmga2 regulates canonical WNT signaling at different points of the pathway. Increased expression of the secreted WNT glycoproteins might explain a paracrine effect by which Hmga2-knockout enhanced cell proliferation in the mesenchyme of the developing lung. In addition, HMGA2-mediated direct regulation of Gata6 is crucial for fine-tuning the activity of WNT signaling in the airway epithelium. Our results are the starting point for future studies investigating the relevance of Hmga2-mediated regulation of

  4. Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors.

    PubMed

    Sreeramkumar, Vinatha; Hons, Miroslav; Punzón, Carmen; Stein, Jens V; Sancho, David; Fresno, Manuel; Cuesta, Natalia

    2016-01-01

    Understanding the regulation of T-cell responses during inflammation and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. In this regard, prostaglandin E2 (PGE2) is mostly considered a myeloid-derived immunosuppressive molecule. We describe for the first time that T cells secrete PGE2 during T-cell receptor stimulation. In addition, we show that autocrine PGE2 signaling through EP receptors is essential for optimal CD4(+) T-cell activation in vitro and in vivo, and for T helper 1 (Th1) and regulatory T cell differentiation. PGE2 was found to provide additive co-stimulatory signaling through AKT activation. Intravital multiphoton microscopy showed that triggering EP receptors in T cells is also essential for the stability of T cell-dendritic cell (DC) interactions and Th-cell accumulation in draining lymph nodes (LNs) during inflammation. We further demonstrated that blocking EP receptors in T cells during the initial phase of collagen-induced arthritis in mice resulted in a reduction of clinical arthritis. This could be attributable to defective T-cell activation, accompanied by a decline in activated and interferon-γ-producing CD4(+) Th1 cells in draining LNs. In conclusion, we prove that T lymphocytes secret picomolar concentrations of PGE2, which in turn provide additive co-stimulatory signaling, enabling T cells to attain a favorable activation threshold. PGE2 signaling in T cells is also required for maintaining long and stable interactions with DCs within LNs. Blockade of EP receptors in vivo impairs T-cell activation and development of T cell-mediated inflammatory responses. This may have implications in various pathophysiological settings.

  5. Sox11 Is Required to Maintain Proper Levels of Hedgehog Signaling during Vertebrate Ocular Morphogenesis

    PubMed Central

    Pillai-Kastoori, Lakshmi; Wen, Wen; Wilson, Stephen G.; Strachan, Erin; Lo-Castro, Adriana; Fichera, Marco; Musumeci, Sebastiano A.; Lehmann, Ordan J.; Morris, Ann C.

    2014-01-01

    Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC) and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders. PMID:25010521

  6. Orthogonal acoustic dimensions define auditory field maps in human cortex.

    PubMed

    Barton, Brian; Venezia, Jonathan H; Saberi, Kourosh; Hickok, Gregory; Brewer, Alyssa A

    2012-12-11

    The functional organization of human auditory cortex has not yet been characterized beyond a rudimentary level of detail. Here, we use functional MRI to measure the microstructure of orthogonal tonotopic and periodotopic gradients forming complete auditory field maps (AFMs) in human core and belt auditory cortex. These AFMs show clear homologies to subfields of auditory cortex identified in nonhuman primates and in human cytoarchitectural studies. In addition, we present measurements of the macrostructural organization of these AFMs into "clover leaf" clusters, consistent with the macrostructural organization seen across human visual cortex. As auditory cortex is at the interface between peripheral hearing and central processes, improved understanding of the organization of this system could open the door to a better understanding of the transformation from auditory spectrotemporal signals to higher-order information such as speech categories.

  7. Effects of multitasking on operator performance using computational and auditory tasks.

    PubMed

    Fasanya, Bankole K

    2016-09-01

    This study investigated the effects of multiple cognitive tasks on human performance. Twenty-four students at North Carolina A&T State University participated in the study. The primary task was auditory signal change perception and the secondary task was a computational task. Results showed that participants' performance in a single task was statistically significantly different from their performance in combined tasks: (a) algebra problems (algebra problem primary and auditory perception secondary); (b) auditory perception tasks (auditory perception primary and algebra problems secondary); and (c) mean false-alarm score in auditory perception (auditory detection primary and algebra problems secondary). Using signal detection theory (SDT), participants' performance measured in terms of sensitivity was calculated as -0.54 for combined tasks (algebra problems the primary task) and -0.53 auditory perceptions the primary task. During auditory perception tasks alone, SDT was found to be 2.51. Performance was 83% in a single task compared to 17% when combined tasks.

  8. IL-17RC is required for immune signaling via an extended SEF/IL-17R signaling domain in the cytoplasmic tail.

    PubMed

    Ho, Allen W; Shen, Fang; Conti, Heather R; Patel, Nayan; Childs, Erin E; Peterson, Alanna C; Hernández-Santos, Nydiaris; Kolls, Jay K; Kane, Lawrence P; Ouyang, Wenjun; Gaffen, Sarah L

    2010-07-15

    IL-17 mediates essential inflammatory responses in host defense and autoimmunity. The IL-17A-IL-17F signaling complex is composed of IL-17RA and IL-17RC, both of which are necessary for signal transduction. To date, the specific contribution of IL-17RC to downstream signaling remains poorly understood. To define the regions within the IL-17RC cytoplasmic tail required for signal transduction, we assayed signaling by a panel of IL-17RC deletion mutants. These findings reveal that IL-17RC inducibly associates with a specific glycosylated IL-17RA isoform, in a manner independent of the IL-17RC cytoplasmic tail. Using expression of the IL-17 target genes IL-6 and 24p3/lipocalin-2 as a readout, functional reconstitution of signaling in IL-17RC(-/-) fibroblasts required the SEF/IL-17R signaling domain (SEFIR), a conserved motif common to IL-17R family members. Unexpectedly, the IL-17RC SEFIR alone was not sufficient to reconstitute IL-17-dependent signaling. Rather, an additional sequence downstream of the SEFIR was also necessary. We further found that IL-17RC interacts directly with the adaptor/E3 ubiquitin ligase Act1, and that the functional IL-17RC isoforms containing the extended SEFIR region interact specifically with a phosphorylated isoform of Act1. Finally, we show that IL-17RC is required for in vivo IL-17-dependent responses during oral mucosal infections caused by the human commensal fungus Candida albicans. These results indicate that IL-17RC is vital for IL-17-dependent signaling both in vitro and in vivo. Insight into the mechanisms by which IL-17RC signals helps shed light on IL-17-dependent inflammatory responses and may ultimately provide an avenue for therapeutic intervention in IL-17-mediated diseases.

  9. Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation

    PubMed Central

    Budi, Erine H.; Patterson, Larissa B.; Parichy, David M.

    2009-01-01

    SUMMARY Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain, or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, encoding an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked-down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development. PMID:18508863

  10. Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

    PubMed

    Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

    2017-09-01

    The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

  11. Electromagnetic recording of the auditory system.

    PubMed

    Poeppel, David; Hickok, Gregory

    2015-01-01

    Auditory processing is remarkably fast and sensitive to the precise temporal structure of acoustic signals over a range of scales, from submillisecond phenomena such as localization to the construction of elementary auditory attributes at tens of milliseconds to basic properties of speech and music at hundreds of milliseconds. In light of the rapid (and often transitory) nature of auditory phenomena, in order to investigate the neurocomputational basis of auditory perception and cognition, a technique with high temporal resolution is appropriate. Here we briefly outline the utility of magnetoencephalography (MEG) for the study of the neural basis of audition. The basics of MEG are outlined in brief, and some of the most-used neural responses are described. We discuss the classic transient evoked fields (e.g., M100), responses elicited by change in a stimulus (e.g., pitch-onset response), the auditory steady-state response, and neural oscillations (e.g., theta-phase tracking). Because of the high temporal resolution and the good spatial resolution of MEG, paired with the convenient location of human auditory cortex for MEG-based recording, electromagnetic recording of this type is well suited to investigate various aspects from audition, from crafted laboratory experiments on pitch perception or scene analysis to naturalistic speech and music tasks. © 2015 Elsevier B.V. All rights reserved.

  12. Electrophysiological measurement of human auditory function

    NASA Technical Reports Server (NTRS)

    Galambos, R.

    1975-01-01

    Knowledge of the human auditory evoked response is reviewed, including methods of determining this response, the way particular changes in the stimulus are coupled to specific changes in the response, and how the state of mind of the listener will influence the response. Important practical applications of this basic knowledge are discussed. Measurement of the brainstem evoked response, for instance, can state unequivocally how well the peripheral auditory apparatus functions. It might then be developed into a useful hearing test, especially for infants and preverbal or nonverbal children. Clinical applications of measuring the brain waves evoked 100 msec and later after the auditory stimulus are undetermined. These waves are clearly related to brain events associated with cognitive processing of acoustic signals, since their properties depend upon where the listener directs his attention and whether how long he expects the signal.

  13. A circuit for motor cortical modulation of auditory cortical activity.

    PubMed

    Nelson, Anders; Schneider, David M; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan; Mooney, Richard

    2013-09-04

    Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity.

  14. A Circuit for Motor Cortical Modulation of Auditory Cortical Activity

    PubMed Central

    Nelson, Anders; Schneider, David M.; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan

    2013-01-01

    Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287

  15. Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction.

    PubMed

    Steventon, Ben; Araya, Claudio; Linker, Claudia; Kuriyama, Sei; Mayor, Roberto

    2009-03-01

    The neural crest is induced by a combination of secreted signals. Although previous models of neural crest induction have proposed a step-wise activation of these signals, the actual spatial and temporal requirement has not been analysed. Through analysing the role of the mesoderm we show for the first time that specification of neural crest requires two temporally and chemically different steps: first, an induction at the gastrula stage dependent on signals arising from the dorsolateral mesoderm; and second, a maintenance step at the neurula stage dependent on signals from tissues adjacent to the neural crest. By performing tissue recombination experiments and using specific inhibitors of different inductive signals, we show that the first inductive step requires Wnt activation and BMP inhibition, whereas the later maintenance step requires activation of both pathways. This change in BMP necessity from BMP inhibition at gastrula to BMP activation at neurula stages is further supported by the dynamic expression of BMP4 and its antagonists, and is confirmed by direct measurements of BMP activity in the neural crest cells. The differential requirements of BMP activity allow us to propose an explanation for apparently discrepant results between chick and frog experiments. The demonstration that Wnt signals are required for neural crest induction by mesoderm solves an additional long-standing controversy. Finally, our results emphasise the importance of considering the order of exposure to signals during an inductive event.

  16. Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.

    PubMed

    Follansbee, Taylor L; Gjelsvik, Kayla J; Brann, Courtney L; McParland, Aidan L; Longhurst, Colin A; Galko, Michael J; Ganter, Geoffrey K

    2017-08-30

    Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans.SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a

  17. Reconstructing Speech from Human Auditory Cortex

    PubMed Central

    Pasley, Brian N.; David, Stephen V.; Mesgarani, Nima; Flinker, Adeen; Shamma, Shihab A.; Crone, Nathan E.; Knight, Robert T.; Chang, Edward F.

    2012-01-01

    How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameters in higher order human auditory cortex. PMID:22303281

  18. Reconstructing speech from human auditory cortex.

    PubMed

    Pasley, Brian N; David, Stephen V; Mesgarani, Nima; Flinker, Adeen; Shamma, Shihab A; Crone, Nathan E; Knight, Robert T; Chang, Edward F

    2012-01-01

    How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameters in higher order human auditory cortex.

  19. Quantitative proteomics of auditory fear conditioning.

    PubMed

    Hong, Ingie; Kang, Taewook; Yun, Ki Na; Yoo, YongCheol; Park, Sungmo; Kim, Jihye; An, Bobae; Song, Sukwoon; Lee, Sukwon; Kim, Jeongyeon; Song, Beomjong; Kwon, Kyung-Hoon; Kim, Jin Young; Park, Young Mok; Choi, Sukwoo

    2013-04-26

    Auditory fear conditioning is a well-characterized rodent learning model where a neutral auditory cue is paired with an aversive outcome to induce associative fear memory. The storage of long-term auditory fear memory requires long-term potentiation (LTP) in the lateral amygdala and de novo protein synthesis. Although many studies focused on individual proteins have shown their contribution to LTP and fear conditioning, non-biased genome-wide studies have only recently been possible with microarrays, which nevertheless fall short of measuring changes at the level of proteins. Here we employed quantitative proteomics to examine the expression of hundreds of proteins in the lateral amygdala in response to auditory fear conditioning. We found that various proteins previously implicated in LTP, learning and axon/dendrite growth were regulated by fear conditioning. A substantial number of proteins that were regulated by fear conditioning have not yet been studied specifically in learning or synaptic plasticity.

  20. The Auditory-Evoked N2 and P3 Components in the Stop-Signal Task: Indices of Inhibition, Response-Conflict or Error-Detection?

    ERIC Educational Resources Information Center

    Dimoska, Aneta; Johnstone, Stuart J.; Barry, Robert J.

    2006-01-01

    The N2 and P3 components have been separately associated with response inhibition in the stop-signal task, and more recently, the N2 has been implicated in the detection of response-conflict. To isolate response inhibition activity from early sensory processing, the present study compared processing of the stop-signal with that of a…

  1. The human brain maintains contradictory and redundant auditory sensory predictions.

    PubMed

    Pieszek, Marika; Widmann, Andreas; Gruber, Thomas; Schröger, Erich

    2013-01-01

    Computational and experimental research has revealed that auditory sensory predictions are derived from regularities of the current environment by using internal generative models. However, so far, what has not been addressed is how the auditory system handles situations giving rise to redundant or even contradictory predictions derived from different sources of information. To this end, we measured error signals in the event-related brain potentials (ERPs) in response to violations of auditory predictions. Sounds could be predicted on the basis of overall probability, i.e., one sound was presented frequently and another sound rarely. Furthermore, each sound was predicted by an informative visual cue. Participants' task was to use the cue and to discriminate the two sounds as fast as possible. Violations of the probability based prediction (i.e., a rare sound) as well as violations of the visual-auditory prediction (i.e., an incongruent sound) elicited error signals in the ERPs (Mismatch Negativity [MMN] and Incongruency Response [IR]). Particular error signals were observed even in case the overall probability and the visual symbol predicted different sounds. That is, the auditory system concurrently maintains and tests contradictory predictions. Moreover, if the same sound was predicted, we observed an additive error signal (scalp potential and primary current density) equaling the sum of the specific error signals. Thus, the auditory system maintains and tolerates functionally independently represented redundant and contradictory predictions. We argue that the auditory system exploits all currently active regularities in order to optimally prepare for future events.

  2. Perceptual consequences of disrupted auditory nerve activity.

    PubMed

    Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

    2005-06-01

    Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique

  3. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

    PubMed

    Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

    2014-01-01

    Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.

  4. Blindness and auditory impairment caused by loss of the sodium bicarbonate cotransporter NBC3.

    PubMed

    Bok, Dean; Galbraith, Gary; Lopez, Ivan; Woodruff, Michael; Nusinowitz, Steven; BeltrandelRio, Hector; Huang, Wenhu; Zhao, Shulei; Geske, Robert; Montgomery, Charles; Van Sligtenhorst, Isaac; Friddle, Carl; Platt, Kenneth; Sparks, Mary Jean; Pushkin, Alexander; Abuladze, Natalia; Ishiyama, Akira; Dukkipati, Ramanath; Liu, Weixin; Kurtz, Ira

    2003-07-01

    Normal sensory transduction requires the efficient disposal of acid (H+) generated by neuronal and sensory receptor activity. Multiple highly sensitive transport mechanisms have evolved in prokaryotic and eukaryotic organisms to maintain acidity within strict limits. It is currently assumed that the multiplicity of these processes provides a biological robustness. Here we report that the visual and auditory systems have a specific requirement for H+ disposal mediated by the sodium bicarbonate cotransporter NBC3 (refs. 7,8). Mice lacking NBC3 develop blindness and auditory impairment because of degeneration of sensory receptors in the eye and inner ear as in Usher syndrome. Our results indicate that in certain sensory organs, in which the requirement to transduce specific environmental signals with speed, sensitivity and reliability is paramount, the choice of the H+ disposal mechanism used is limited.

  5. Melanocortin-4 Receptor Signaling Is Required for Weight Loss after Gastric Bypass Surgery

    PubMed Central

    Hatoum, Ida J.; Stylopoulos, Nicholas; Vanhoose, Amanda M.; Boyd, Kelli L.; Yin, Deng Ping; Ellacott, Kate L. J.; Ma, Lian Li; Blaszczyk, Kasia; Keogh, Julia M.; Cone, Roger D.; Farooqi, I. Sadaf

    2012-01-01

    Context: Roux-en-Y gastric bypass (RYGB) is one of the most effective long-term therapies for the treatment of severe obesity. Recent evidence indicates that RYGB effects weight loss through multiple physiological mechanisms, including changes in energy expenditure, food intake, food preference, and reward pathways. Objective: Because central melanocortin signaling plays an important role in the regulation of energy homeostasis, we investigated whether genetic disruption of the melanocortin-4 receptor (MC4R) in rodents and humans affects weight loss after RYGB. Methods and Results: Here we report that MC4R−/− mice lost substantially less weight after surgery than wild-type animals, indicating that MC4R signaling is necessary for the weight loss effects of RYGB in this model. Mice heterozygous for MC4R remain fully responsive to gastric bypass. To determine whether mutations affect surgically induced weight loss in humans, we sequenced the MC4R gene in 972 patients undergoing RYGB. Patients heterozygous for MC4R mutations exhibited the same magnitude and distribution of postoperative weight loss as patients without such mutations, suggesting that although two normal copies of the MC4R gene are necessary for normal weight regulation, a single normal copy of the MC4R gene is sufficient to mediate the weight loss effects of RYGB. Conclusions: MC4R is the first gene identified that is required for the sustained effects of bariatric surgery. The need for MC4R signaling for the weight loss effects of RYGB in mice underscores the physiological mechanisms of action of this procedure and demonstrates that RYGB both influences and is dependent on the normal pathways that regulate energy balance. PMID:22492873

  6. Lysophosphatidic Acid Signaling through the Lysophosphatidic Acid-1 Receptor Is Required for Alveolarization.

    PubMed

    Funke, Manuela; Knudsen, Lars; Lagares, David; Ebener, Simone; Probst, Clemens K; Fontaine, Benjamin A; Franklin, Alicia; Kellner, Manuela; Kühnel, Mark; Matthieu, Stephanie; Grothausmann, Roman; Chun, Jerold; Roberts, Jesse D; Ochs, Matthias; Tager, Andrew M

    2016-07-01

    Lysophosphatidic acid (LPA) signaling through one of its receptors, LPA1, contributes to both the development and the pathological remodeling after injury of many organs. Because we found previously that LPA-LPA1 signaling contributes to pulmonary fibrosis, here we investigated whether this pathway is also involved in lung development. Quantitative assessment of lung architecture of LPA1-deficient knock-out (KO) and wild-type (WT) mice at 3, 12, and 24 weeks of age using design-based stereology suggested the presence of an alveolarization defect in LPA1 KO mice at 3 weeks, which persisted as alveolar numbers increased in WT mice into adulthood. Across the ages examined, the lungs of LPA1 KO mice exhibited decreased alveolar numbers, septal tissue volumes, and surface areas, and increased volumes of the distal airspaces. Elastic fibers, critical to the development of alveolar septa, appeared less organized and condensed and more discontinuous in KO alveoli starting at P4. Tropoelastin messenger RNA expression was decreased in KO lungs, whereas expression of matrix metalloproteinases degrading elastic fibers was either decreased or unchanged. These results are consistent with the abnormal lung phenotype of LPA1 KO mice, being attributable to reduced alveolar septal formation during development, rather than to increased septal destruction as occurs in the emphysema of chronic obstructive pulmonary disease. Peripheral septal fibroblasts and myofibroblasts, which direct septation in late alveolarization, demonstrated reduced production of tropoelastin and matrix metalloproteinases, and diminished LPA-induced migration, when isolated from LPA1 KO mice. Taken together, our data suggest that LPA-LPA1 signaling is critically required for septation during alveolarization.

  7. Requirements for Mouse Mammary Tumor Virus Rem Signal Peptide Processing and Function

    PubMed Central

    Byun, Hyewon; Halani, Nimita; Gou, Yongqiang; Nash, Andrea K.; Lozano, Mary M.

    2012-01-01

    Mouse mammary tumor virus (MMTV) encodes a Rev-like protein, Rem, which is involved in the nuclear export and expression of viral RNA. Previous data have shown that all Rev-like functions are localized to the 98-amino-acid signal peptide (SP) at the N terminus of MMTV Rem or envelope proteins. MMTV-SP uses endoplasmic reticulum-associated degradation (ERAD) for protein trafficking. Rem cleavage by signal peptidase in the ER is necessary for MMTV-SP function in a reporter assay, but many requirements for trafficking are not known. To allow detection and localization of both MMTV-SP and the C-terminal cleavage product, we prepared plasmids expressing green fluorescent protein (GFP) tags. N-terminal Rem tagging led to protein accumulation relative to untagged Rem and allowed signal peptidase cleavage but reduced its specific activity. C-terminal tagging also led to Rem accumulation yet dramatically reduced cleavage, GFP fluorescence, and activity relative to N-terminally tagged Rem (GFPRem). Substitutions of an invariant leucine at position 71 between the known RNA-binding and nuclear export sequences interfered with GFPRem accumulation and activity but not cleavage. Similarly, deletion of 100 or 150 C-terminal amino acids from GFPRem dramatically reduced both Rem and MMTV-SP levels and function. Removal of the entire C terminus (203 amino acids) restored both protein levels and activity of MMTV-SP. Only C-terminal GFP tagging, and not other modifications, appeared to trap Rem in the ER membrane. Thus, Rem conformation in both the ER lumen and cytoplasm determines cleavage, retrotranslocation, and MMTV-SP function. These mutants further characterize intermediates in Rem trafficking and have implications for all proteins affected by ERAD. PMID:22072771

  8. Aspergillus nidulans Ambient pH Signaling Does Not Require Endocytosis

    PubMed Central

    Lucena-Agell, Daniel; Galindo, Antonio; Arst, Herbert N.

    2015-01-01

    Aspergillus nidulans (Pal) ambient pH signaling takes place in cortical structures containing components of the ESCRT pathway, which are hijacked by the alkaline pH-activated, ubiquitin-modified version of the arrestin-like protein PalF and taken to the plasma membrane. There, ESCRTs scaffold the assembly of dedicated Pal proteins acting downstream. The molecular details of this pathway, which results in the two-step proteolytic processing of the transcription factor PacC, have received considerable attention due to the key role that it plays in fungal pathogenicity. While current evidence strongly indicates that the pH signaling role of ESCRT complexes is limited to plasma membrane-associated structures where PacC proteolysis would take place, the localization of the PalB protease, which almost certainly catalyzes the first and only pH-regulated proteolytic step, had not been investigated. In view of ESCRT participation, this formally leaves open the possibility that PalB activation requires endocytic internalization. As endocytosis is essential for hyphal growth, nonlethal endocytic mutations are predicted to cause an incomplete block. We used a SynA internalization assay to measure the extent to which any given mutation prevents endocytosis. We show that none of the tested mutations impairing endocytosis to different degrees, including slaB1, conditionally causing a complete block, have any effect on the activation of the pathway. We further show that PalB, like PalA and PalC, localizes to cortical structures in an alkaline pH-dependent manner. Therefore, signaling through the Pal pathway does not involve endocytosis. PMID:25841020

  9. Endogenous BMPR-IB signaling is required for early osteoblast differentiation of human bone cells.

    PubMed

    Singhatanadgit, Weerachai; Olsen, Irwin

    2011-03-01

    Osteoblast differentiation is tightly regulated by a number of cytokines and growth factors, including bone morphogenetic proteins (BMP) which stimulate osteoblast differentiation by signal transduction via three BMP receptors (BMPR-IA, -IB and -II). Although the mechanisms which regulate osteoblast differentiation are not fully understood, it is possible that endogenous BMPR signaling could play an important part in this process. To test this hypothesis, we have examined the expression and the functional significance of BMPR during osteoblast differentiation of primary human bone cells. The results showed that although the expression of BMPR-IA and -II transcripts were constantly expressed while the bone cells underwent osteoblast differentiation, the level of BMPR-IB mRNA was transiently, but significantly, up-regulated by threefold on day 3. This increase in BMPR-IB expression was found to be associated with the significant up-regulation of core binding factor alpha 1 (Cbfa1) and alkaline phosphatase (ALP) transcripts as well as the ALP activity, the well-established early markers of osteoblast differentiation. Transfection of bone cells with BMPR-IB small interfering RNA (siRNA) was found to significantly ablate the expression of BMPR-IB which subsequently resulted in reduction of Cbfa1 and ALP mRNA as well as the ALP activity. Moreover, exogenously added BMP-2 failed to rescue osteoblast differentiation of BMPR-IB siRNA-transfected bone cells. In conclusion, the present study has shown that endogenous BMPR-IB signaling is required for early phase of osteoblast differentiation of human bone cells in vitro, suggesting that BMPR-IB could be a therapeutic target for initiating bone healing in vivo.

  10. Does murine spermatogenesis require WNT signalling? A lesson from Gpr177 conditional knockout mouse models.

    PubMed

    Chen, Su-Ren; Tang, J-X; Cheng, J-M; Hao, X-X; Wang, Y-Q; Wang, X-X; Liu, Y-X

    2016-06-30

    Wingless-related MMTV integration site (WNT) proteins and several other components of the WNT signalling pathway are expressed in the murine testes. However, mice mutant for WNT signalling effector β-catenin using different Cre drivers have phenotypes that are inconsistent with each other. The complexity and overlapping expression of WNT signalling cascades have prevented researchers from dissecting their function in spermatogenesis. Depletion of the Gpr177 gene (the mouse orthologue of Drosophila Wntless), which is required for the secretion of various WNTs, makes it possible to genetically dissect the overall effect of WNTs in testis development. In this study, the Gpr177 gene was conditionally depleted in germ cells (Gpr177(flox/flox), Mvh-Cre; Gpr177(flox/flox), Stra8-Cre) and Sertoli cells (Gpr177(flox/flox), Amh-Cre). No obvious defects in fertility and spermatogenesis were observed in these three Gpr177 conditional knockout (cKO) mice at 8 weeks. However, late-onset testicular atrophy and fertility decline in two germ cell-specific Gpr177 deletion mice were noted at 8 months. In contrast, we did not observe any abnormalities of spermatogenesis and fertility, even in 8-month-old Gpr177(flox/flox), Amh-Cre mice. Elevation of reactive oxygen species (ROS) was detected in Gpr177 cKO germ cells and Sertoli cells and exhibited an age-dependent manner. However, significant increase in the activity of Caspase 3 was only observed in germ cells from 8-month-old germ cell-specific Gpr177 knockout mice. In conclusion, GPR177 in Sertoli cells had no apparent influence on spermatogenesis, whereas loss of GPR177 in germ cells disrupted spermatogenesis in an age-dependent manner via elevating ROS levels and triggering germ cell apoptosis.

  11. ErbB2-dependent chemotaxis requires microtubule capture and stabilization coordinated by distinct signaling pathways.

    PubMed

    Benseddik, Khedidja; Sen Nkwe, Nadine; Daou, Pascale; Verdier-Pinard, Pascal; Badache, Ali

    2013-01-01

    Activation of the ErbB2 receptor tyrosine kinase stimulates breast cancer cell migration. Cell migration is a complex process that requires the synchronized reorganization of numerous subcellular structures including cell-to-matrix adhesions, the actin cytoskeleton and microtubules. How the multiple signaling pathways triggered by ErbB2 coordinate, in time and space, the various processes involved in cell motility, is poorly defined. We investigated the mechanism whereby ErbB2 controls microtubules and chemotaxis. We report that activation of ErbB2 increased both cell velocity and directed migration. Impairment of the Cdc42 and RhoA GTPases, but not of Rac1, prevented the chemotactic response. RhoA is a key component of the Memo/ACF7 pathway whereby ErbB2 controls microtubule capture at the leading edge. Upon Memo or ACF7 depletion, microtubules failed to reach the leading edge and cells lost their ability to follow the chemotactic gradient. Constitutive ACF7 targeting to the membrane in Memo-depleted cells reestablished directed migration. ErbB2-mediated activation of phospholipase C gamma (PLCγ) also contributed to cell guidance. We further showed that PLCγ signaling, via classical protein kinases C, and Memo signaling converged towards a single pathway controlling the microtubule capture complex. Finally, inhibiting the PI3K/Akt pathway did not affect microtubule capture, but disturbed microtubule stability, which also resulted in defective chemotaxis. PI3K/Akt-dependent stabilization of microtubules involved repression of GSK3 activity on the one hand and inhibition of the microtubule destabilizing protein, Stathmin, on the other hand. Thus, ErbB2 triggers distinct and complementary pathways that tightly coordinate microtubule capture and microtubule stability to control chemotaxis.

  12. Leptin Signaling Is Not Required for Anorexigenic Estradiol Effects in Female Mice.

    PubMed

    Kim, Joon S; Rizwan, Mohammed Z; Clegg, Deborah J; Anderson, Greg M

    2016-05-01

    Estradiol and leptin are critical hormones in the regulation of body weight. The aim of this study was to determine whether this cross talk between leptin receptor (LepRb) and estrogen receptor-α (ERα) signaling is critical for estradiol's anorexigenic effects. Leprb-Cre mice were crossed with Cre-dependent Tau-green fluorescent protein (GFP) reporter, Stat3-flox or Erα-flox mice to generate female mice with GFP expression, signal transducer and activator of transcription 3 (STAT3) knockout (KO), or ERα KO, specifically in LepRb-expressing cells. The proportion of Leprb-GFP cells colocalizing ERα was high (∼80%) in the preoptic area but low (∼10%) in the mediobasal hypothalamus, suggesting that intracellular cross talk between these receptors is minimal for metabolic regulation. To test whether estradiol enhanced arcuate leptin sensitivity, ovarectomized mice received varying levels of estradiol replacement. Increasing estrogenic states did not increase the degree of leptin-induced STAT3 phosphorylation. LepRb-specific STAT3 KO mice and controls were ovarectomized and given either chronic estradiol or vehicle treatment to test whether STAT3 is required for estrogen-induced body weight suppression. Both groups of estradiol-treated mice showed an equivalent reduction in body weight and fat content compared with vehicle controls. Finally, mice lacking ERα specifically in LepRb-expressing neurons also showed no increase in body weight or impairments in metabolic function compared with controls, indicating that estradiol acts independently of leptin-responsive cells to regulate body weight. However, fecundity was impaired in in Leprb-ERα KO females. Contrary to the current dogma, we report that estradiol has minimal direct actions on LepRb cells in the mediodasal hypothalamus and that its anorexigenic effects can occur entirely independently of LepRb-STAT3 signaling in female mice.

  13. Does murine spermatogenesis require WNT signalling? A lesson from Gpr177 conditional knockout mouse models

    PubMed Central

    Chen, Su-Ren; Tang, J-X; Cheng, J-M; Hao, X-X; Wang, Y-Q; Wang, X-X; Liu, Y-X

    2016-01-01

    Wingless-related MMTV integration site (WNT) proteins and several other components of the WNT signalling pathway are expressed in the murine testes. However, mice mutant for WNT signalling effector β-catenin using different Cre drivers have phenotypes that are inconsistent with each other. The complexity and overlapping expression of WNT signalling cascades have prevented researchers from dissecting their function in spermatogenesis. Depletion of the Gpr177 gene (the mouse orthologue of Drosophila Wntless), which is required for the secretion of various WNTs, makes it possible to genetically dissect the overall effect of WNTs in testis development. In this study, the Gpr177 gene was conditionally depleted in germ cells (Gpr177flox/flox, Mvh-Cre; Gpr177flox/flox, Stra8-Cre) and Sertoli cells (Gpr177flox/flox, Amh-Cre). No obvious defects in fertility and spermatogenesis were observed in these three Gpr177 conditional knockout (cKO) mice at 8 weeks. However, late-onset testicular atrophy and fertility decline in two germ cell-specific Gpr177 deletion mice were noted at 8 months. In contrast, we did not observe any abnormalities of spermatogenesis and fertility, even in 8-month-old Gpr177flox/flox, Amh-Cre mice. Elevation of reactive oxygen species (ROS) was detected in Gpr177 cKO germ cells and Sertoli cells and exhibited an age-dependent manner. However, significant increase in the activity of Caspase 3 was only observed in germ cells from 8-month-old germ cell-specific Gpr177 knockout mice. In conclusion, GPR177 in Sertoli cells had no apparent influence on spermatogenesis, whereas loss of GPR177 in germ cells disrupted spermatogenesis in an age-dependent manner via elevating ROS levels and triggering germ cell apoptosis. PMID:27362799

  14. Requirement of Tumor Necrosis Factor Receptor–Associated Factor (Traf)6 in Interleukin 17 Signal Transduction

    PubMed Central

    Schwandner, Ralf; Yamaguchi, Kyoko; Cao, Zhaodan

    2000-01-01

    Signaling through its widely distributed cell surface receptor, interleukin (IL)-17 enhances the transcription of genes encoding proinflammatory molecules. Although it has been well documented that IL-17 activates the transcription factor nuclear factor (NF)-κB and c-Jun NH2-terminal kinase (JNK), the upstream signaling events are largely unknown. Here we report the requirement of tumor necrosis factor receptor–associated factor (TRAF)6 in IL-17–induced NF-κB and JNK activation. In embryonic fibroblasts (EFs) derived from TRAF6 knockout mice, IL-17 failed to activate the IκB kinases (IKKs) and JNK. Consequently, IL-17–induced IL-6 and intercellular adhesion molecule 1 expression in the TRAF6-deficient cells was abolished. Lack of TRAF6 appeared to be the sole defect responsible for the observed failure to respond to IL-17, because transient transfection of TRAF6 expression plasmid into the TRAF6-deficient cells restored IL-17–induced NF-κB activation in a luciferase reporter assay. Furthermore, the levels of IL-17 receptor (IL-17R) on the TRAF6-deficient EFs were comparable to those on the wild-type control cells. Defect in IL-17 response was not observed in TRAF2-deficient EFs. Moreover, when TRAF6 and IL-17R were coexpressed in 293 cells, TRAF6 coimmunoprecipitated with IL-17R. Together, these results indicate that TRAF6, but not TRAF2, is a crucial component in the IL-17 signaling pathway leading to proinflammatory responses. PMID:10748240

  15. Analysis of satellite altimeter signal characteristics and investigation of sea-truth data requirements

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Results are presented of analysis of satellite signal characteristics as influenced by ocean surface roughness and an investigation of sea truth data requirements. The first subject treated is that of postflight waveform reconstruction for the Skylab S-193 radar altimeter. Sea state estimation accuracies are derived based on analytical and hybrid computer simulation techniques. An analysis of near-normal incidence, microwave backscattering from the ocean's surface is accomplished in order to obtain the minimum sea truth data necessary for good agreement between theoretical and experimental scattering results. Sea state bias is examined from the point of view of designing an experiment which will lead to a resolution of the problem. A discussion is given of some deficiencies which were found in the theory underlying the Stilwell technique for spectral measurements.

  16. Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling.

    PubMed

    Noland, Cameron L; Gierke, Sarah; Schnier, Paul D; Murray, Jeremy; Sandoval, Wendy N; Sagolla, Meredith; Dey, Anwesha; Hannoush, Rami N; Fairbrother, Wayne J; Cunningham, Christian N

    2016-01-05

    The Hippo signaling pathway is responsible for regulating the function of TEAD family transcription factors in metazoans. TEADs, with their co-activators YAP/TAZ, are critical for controlling cell differentiation and organ size through their transcriptional activation of genes involved in cell growth and proliferation. Dysregulation of the Hippo pathway has been implicated in multiple forms of cancer. Here, we identify a novel form of regulation of TEAD family proteins. We show that human TEADs are palmitoylated at a universally conserved cysteine, and report the crystal structures of the human TEAD2 and TEAD3 YAP-binding domains in their palmitoylated forms. These structures show a palmitate bound within a highly conserved hydrophobic cavity at each protein's core. Our findings also demonstrate that this modification is required for proper TEAD folding and stability, indicating a potential new avenue for pharmacologically regulating the Hippo pathway through the modulation of TEAD palmitoylation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Serotonin signaling in the brain of adult female mice is required for sexual preference

    PubMed Central

    Zhang, Shasha; Liu, Yan; Rao, Yi

    2013-01-01

    A role for serotonin in male sexual preference was recently uncovered by our finding that male mutant mice lacking serotonin have lost sexual preference. Here we show that female mouse mutants lacking either central serotonergic neurons or serotonin prefer female over male genital odors when given a choice, and displayed increased female–female mounting when presented either with a choice of a male and a female target or only with a female target. Pharmacological manipulations and genetic rescue experiments showed that serotonin is required in adults. Behavioral changes caused by deficient serotonergic signaling were not due to changes in plasma concentrations of sex hormones. We demonstrate that a genetic manipulation reverses sexual preference without involving sex hormones. Our results indicate that serotonin controls sexual preference. PMID:23716677

  18. Ethylene signaling is required for synergid degeneration and the establishment of a pollen tube block.

    PubMed

    Völz, Ronny; Heydlauff, Juliane; Ripper, Dagmar; von Lyncker, Ludwig; Groß-Hardt, Rita

    2013-05-13

    In flowering plants, sperm cells are delivered by pollen tubes, which are attracted by two egg-cell-adjoining synergids. Successful fertilization terminates pollen tube attraction; however, the underlying mechanisms are not understood. Here, we show that the process of fertilization activates an EIN3- and EIN2-dependent ethylene-response cascade necessary for synergid cell death and the concomitant establishment of a pollen tube block. Microinjection of the ethylene precursor ACC into the female gametophyte or constitutive ethylene response results in premature synergid disintegration. This indicates that the requirement of fertilization for synergid degeneration and associated establishment of a pollen tube block can be bypassed by mimicking a postfertilization ethylene burst. Surprisingly, the persistent synergid in ethylene-hyposensitive plants adopts the molecular profile and cell-cycle regime of the biparental embryo-nourishing tissue, suggesting that ethylene signaling prevents the formation of an asexual maternal endosperm fraction.

  19. Ethylene signaling pathway and MAPK cascades are required for AAL toxin-induced programmed cell death.

    PubMed

    Mase, Keisuke; Mizuno, Takahito; Ishihama, Nobuaki; Fujii, Takayuki; Mori, Hitoshi; Kodama, Motoichiro; Yoshioka, Hirofumi

    2012-08-01

    Programmed cell death (PCD), known as hypersensitive response cell death, has an important role in plant defense response. The signaling pathway of PCD remains unknown. We employed AAL toxin and Nicotiana umbratica to analysis plant PCD. AAL toxin is a pathogenicity factor of the necrotrophic pathogen Alternaria alternata f. sp. lycopersici. N. umbratica is sensitive to AAL toxin, susceptible to pathogens, and effective in Tobacco rattle virus-based virus-induced gene silencing (VIGS). VIGS analyses indicated that AAL toxin-triggered cell death (ACD) is dependent upon the mitogen-activated protein (MAP) kinase kinase MEK2, which is upstream of both salicylic acid-induced protein kinase (SIPK) and wound-induced protein kinase (WIPK) responsible for ethylene (ET) synthesis. ET treatment of MEK2-silenced N. umbratica re-established ACD. In SIPK- and WIPK-silenced N. umbratica, ACD was compromised and ET accumulation was not observed. However, in contrast to the case of MEK2-silenced plants, ET treatment did not induce cell death in SIPK- and WIPK-silenced plants. This work showed that ET-dependent pathway and MAP kinase cascades are required in ACD. Our results suggested that MEK2-SIPK/WIPK cascades have roles in ET biosynthesis; however, SIPK and WIPK have other roles in ET signaling or another pathway leading to cell death by AAL toxin.

  20. MD-2 is required for disulfide HMGB1-dependent TLR4 signaling.

    PubMed

    Yang, Huan; Wang, Haichao; Ju, Zhongliang; Ragab, Ahmed A; Lundbäck, Peter; Long, Wei; Valdes-Ferrer, Sergio I; He, Mingzhu; Pribis, John P; Li, Jianhua; Lu, Ben; Gero, Domokos; Szabo, Csaba; Antoine, Daniel J; Harris, Helena E; Golenbock, Doug T; Meng, Jianmin; Roth, Jesse; Chavan, Sangeeta S; Andersson, Ulf; Billiar, Timothy R; Tracey, Kevin J; Al-Abed, Yousef

    2015-01-12

    Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2-deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2-HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4-MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness.

  1. MD-2 is required for disulfide HMGB1–dependent TLR4 signaling

    PubMed Central

    Wang, Haichao; Ju, Zhongliang; Ragab, Ahmed A.; Lundbäck, Peter; Long, Wei; Valdes-Ferrer, Sergio I.; He, Mingzhu; Pribis, John P.; Li, Jianhua; Lu, Ben; Gero, Domokos; Szabo, Csaba; Antoine, Daniel J.; Harris, Helena E.; Golenbock, Doug T.; Meng, Jianmin; Roth, Jesse; Chavan, Sangeeta S.; Andersson, Ulf; Billiar, Timothy R.; Al-Abed, Yousef

    2015-01-01

    Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2–deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2–HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4–MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness. PMID:25559892

  2. Auditory perceptual restoration and illusory continuity correlates in the human brainstem.

    PubMed

    Bidelman, Gavin M; Patro, Chhayakanta

    2016-09-01

    When noise obstructs portions of target sounds the auditory system fills in missing information, a phenomenon known as auditory restoration or induction. Previous work in animal models demonstrates that neurons in primary auditory cortex (A1) are capable of restoring occluded target signals suggesting that early auditory cortex is capable of inducing continuity in discontinuous signals (i.e., endogenous restoration). Current consensus is that the neural correlates of auditory induction and perceptual restoration emerge no earlier than A1. Moreover, the neural mechanisms supporting induction in humans are poorly understood. Here, we show that in human listeners, auditory brainstem nuclei support illusory auditory continuity well before engagement of cerebral cortex. We recorded brainstem responses to modulated target tones that did or did not promote illusory auditory percepts. Auditory continuity was manipulated by introducing masking noise or brief temporal interruptions in otherwise continuous tones. We found that auditory brainstem responses paralleled illusory continuity by tagging target sounds even when they were occluded by the auditory scene. Our results reveal (i) a pre-attentive, subcortical origin to a presumed cortical function and (ii) that brainstem signal processing helps partially cancel the negative effects of masking by restoring missing portions of auditory objects that are fragmented in the soundscape.

  3. Facilitated auditory detection for speech sounds.

    PubMed

    Signoret, Carine; Gaudrain, Etienne; Tillmann, Barbara; Grimault, Nicolas; Perrin, Fabien

    2011-01-01

    If it is well known that knowledge facilitates higher cognitive functions, such as visual and auditory word recognition, little is known about the influence of knowledge on detection, particularly in the auditory modality. Our study tested the influence of phonological and lexical knowledge on auditory detection. Words, pseudo-words, and complex non-phonological sounds, energetically matched as closely as possible, were presented at a range of presentation levels from sub-threshold to clearly audible. The participants performed a detection task (Experiments 1 and 2) that was followed by a two alternative forced-choice recognition task in Experiment 2. The results of this second task in Experiment 2 suggest a correct recognition of words in the absence of detection with a subjective threshold approach. In the detection task of both experiments, phonological stimuli (words and pseudo-words) were better detected than non-phonological stimuli (complex sounds), presented close to the auditory threshold. This finding suggests an advantage of speech for signal detection. An additional advantage of words over pseudo-words was observed in Experiment 2, suggesting that lexical knowledge could also improve auditory detection when listeners had to recognize the stimulus in a subsequent task. Two simulations of detection performance performed on the sound signals confirmed that the advantage of speech over non-speech processing could not be attributed to energetic differences in the stimuli.

  4. Neural correlates of auditory temporal predictions during sensorimotor synchronization

    PubMed Central

    Pecenka, Nadine; Engel, Annerose; Keller, Peter E.

    2013-01-01

    Musical ensemble performance requires temporally precise interpersonal action coordination. To play in synchrony, ensemble musicians presumably rely on anticipatory mechanisms that enable them to predict the timing of sounds produced by co-performers. Previous studies have shown that individuals differ in their ability to predict upcoming tempo changes in paced finger-tapping tasks (indexed by cross-correlations between tap timing and pacing events) and that the degree of such prediction influences the accuracy of sensorimotor synchronization (SMS) and interpersonal coordination in dyadic tapping tasks. The current functional magnetic resonance imaging study investigated the neural correlates of auditory temporal predictions during SMS in a within-subject design. Hemodynamic responses were recorded from 18 musicians while they tapped in synchrony with auditory sequences containing gradual tempo changes under conditions of varying cognitive load (achieved by a simultaneous visual n-back working-memory task comprising three levels of difficulty: observation only, 1-back, and 2-back object comparisons). Prediction ability during SMS decreased with increasing cognitive load. Results of a parametric analysis revealed that the generation of auditory temporal predictions during SMS recruits (1) a distributed network of cortico-cerebellar motor-related brain areas (left dorsal premotor and motor cortex, right lateral cerebellum, SMA proper and bilateral inferior parietal cortex) and (2) medial cortical areas (medial prefrontal cortex, posterior cingulate cortex). While the first network is presumably involved in basic sensory prediction, sensorimotor integration, motor timing, and temporal adaptation, activation in the second set of areas may be related to higher-level social-cognitive processes elicited during action coordination with auditory signals that resemble music performed by human agents. PMID:23970857

  5. Neural correlates of auditory temporal predictions during sensorimotor synchronization.

    PubMed

    Pecenka, Nadine; Engel, Annerose; Keller, Peter E

    2013-01-01

    Musical ensemble performance requires temporally precise interpersonal action coordination. To play in synchrony, ensemble musicians presumably rely on anticipatory mechanisms that enable them to predict the timing of sounds produced by co-performers. Previous studies have shown that individuals differ in their ability to predict upcoming tempo changes in paced finger-tapping tasks (indexed by cross-correlations between tap timing and pacing events) and that the degree of such prediction influences the accuracy of sensorimotor synchronization (SMS) and interpersonal coordination in dyadic tapping tasks. The current functional magnetic resonance imaging study investigated the neural correlates of auditory temporal predictions during SMS in a within-subject design. Hemodynamic responses were recorded from 18 musicians while they tapped in synchrony with auditory sequences containing gradual tempo changes under conditions of varying cognitive load (achieved by a simultaneous visual n-back working-memory task comprising three levels of difficulty: observation only, 1-back, and 2-back object comparisons). Prediction ability during SMS decreased with increasing cognitive load. Results of a parametric analysis revealed that the generation of auditory temporal predictions during SMS recruits (1) a distributed network of cortico-cerebellar motor-related brain areas (left dorsal premotor and motor cortex, right lateral cerebellum, SMA proper and bilateral inferior parietal cortex) and (2) medial cortical areas (medial prefrontal cortex, posterior cingulate cortex). While the first network is presumably involved in basic sensory prediction, sensorimotor integration, motor timing, and temporal adaptation, activation in the second set of areas may be related to higher-level social-cognitive processes elicited during action coordination with auditory signals that resemble music performed by human agents.

  6. Auditory-motor learning influences auditory memory for music.

    PubMed

    Brown, Rachel M; Palmer, Caroline

    2012-05-01

    In two experiments, we investigated how auditory-motor learning influences performers' memory for music. Skilled pianists learned novel melodies in four conditions: auditory only (listening), motor only (performing without sound), strongly coupled auditory-motor (normal performance), and weakly coupled auditory-motor (performing along with auditory recordings). Pianists' recognition of the learned melodies was better following auditory-only or auditory-motor (weakly coupled and strongly coupled) learning than following motor-only learning, and better following strongly coupled auditory-motor learning than following auditory-only learning. Auditory and motor imagery abilities modulated the learning effects: Pianists with high auditory imagery scores had better recognition following motor-only learning, suggesting that auditory imagery compensated for missing auditory feedback at the learning stage. Experiment 2 replicated the findings of Experiment 1 with melodies that contained greater variation in acoustic features. Melodies that were slower and less variable in tempo and intensity were remembered better following weakly coupled auditory-motor learning. These findings suggest that motor learning can aid performers' auditory recognition of music beyond auditory learning alone, and that motor learning is influenced by individual abilities in mental imagery and by variation in acoustic features.

  7. CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins.

    PubMed

    Cimo, Ann-Marie; Ahmed, Zamal; McIntyre, Bradley W; Lewis, Dorothy E; Ladbury, John E

    2013-08-15

    Distinct signalling pathways producing diverse cellular outcomes can utilize similar subsets of proteins. For example, proteins from the TCR (T-cell receptor) ESC (early signalling complex) are also involved in interferon-α receptor signalling. Defining the mechanism for how these proteins function within a given pathway is important in understanding the integration and communication of signalling networks with one another. We investigated the contributions of the TCR ESC proteins Lck (lymphocyte-specific kinase), ZAP-70 (ζ-chain-associated protein of 70 kDa), Vav1, SLP-76 [SH2 (Src homology 2)-domain-containing leukocyte protein of 76 kDa] and LAT (linker for activation of T-cells) to integrin outside-in signalling in human T-cells. Lck, ZAP-70, SLP-76, Vav1 and LAT were activated by α4β1 outside-in signalling, but in a manner different from TCR signalling. TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). α4β1 outside-in-mediated ERK activation did not require TCR ESC proteins. However, α4β1 outside-in signalling induced CD25 and co-stimulated CD69 and this was dependent on TCR ESC proteins. TCR and α4β1 outside-in signalling are integrated through the common use of TCR ESC proteins; however, these proteins display functionally distinct roles in these pathways. These novel insights into the cross-talk between integrin outside-in and TCR signalling pathways are highly relevant to the development of therapeutic strategies to overcome disease associated with T-cell deregulation.

  8. Psychology of auditory perception.

    PubMed

    Lotto, Andrew; Holt, Lori

    2011-09-01

    Audition is often treated as a 'secondary' sensory system behind vision in the study of cognitive science. In this review, we focus on three seemingly simple perceptual tasks to demonstrate the complexity of perceptual-cognitive processing involved in everyday audition. After providing a short overview of the characteristics of sound and their neural encoding, we present a description of the perceptual task of segregating multiple sound events that are mixed together in the signal reaching the ears. Then, we discuss the ability to localize the sound source in the environment. Finally, we provide some data and theory on how listeners categorize complex sounds, such as speech. In particular, we present research on how listeners weigh multiple acoustic cues in making a categorization decision. One conclusion of this review is that it is time for auditory cognitive science to be developed to match what has been done in vision in order for us to better understand how humans communicate with speech and music. WIREs Cogni Sci 2011 2 479-489 DOI: 10.1002/wcs.123 For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  9. Biological impact of music and software-based auditory training.

    PubMed

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals - both young and old - encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based training can improve these biological signals. These findings of biological plasticity, in a variety of subject populations, relate to attention and auditory memory, and represent an integrated auditory system influenced by both sensation and cognition.

  10. Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation.

    PubMed

    Maharam, Edward; Yaport, Miguel; Villanueva, Nathaniel L; Akinyibi, Takintope; Laudier, Damien; He, Zhiyong; Leong, Daniel J; Sun, Hui B

    2015-01-01

    Mesenchymal stem cell (MSC)-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin (two other components of the pathway) using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.

  11. Transcription-dependent nuclear localization of DAZAP1 requires an N-terminal signal

    SciTech Connect

    Lin, Yi-Tzu; Wen, Wan-Ching; Yen, Pauline H.

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer DAZAP1 shuttles between the nucleus and the cytoplasm. Black-Right-Pointing-Pointer DAZAP1 accumulates in the cytoplasm when the nuclear transcription is inhibited. Black-Right-Pointing-Pointer DAZAP1's transcription-dependent nuclear localization requires N-terminal N42. Black-Right-Pointing-Pointer SLIRP binds to N42 and may be involved in the process. -- Abstract: Deleted in Azoospermia Associated Protein 1 (DAZAP1) is a ubiquitous hnRNP protein required for normal development and spermatogenesis. It resides predominantly in the nucleus and moves between the nucleus and the cytoplasm via a ZNS shuttling signal at its C-terminus. DAZAP1 accumulates in the cytoplasm when RNA polymerase II activity is inhibited by actinomycin D. Here we report the mapping of a 42-amino acid segment (N42) at the N-terminus of DAZAP1 that is both necessary and sufficient for its transcription-dependent nuclear localization. In addition, using a yeast two-hybrid system, we have identified SLIRP as a N42-binding protein which may regulate DAZAP1 subcellular localization.

  12. Porcupine homolog is required for canonical Wnt signaling and gastrulation in mouse embryos.

    PubMed

    Biechele, Steffen; Cox, Brian J; Rossant, Janet

    2011-07-15

    Wnt signaling plays important roles in development and disease. The X-chromosomal Porcupine homolog gene (Porcn) encodes an evolutionary conserved member of the membrane bound O-acyl transferase (MBOAT) superfamily that has been shown to be required for the palmitoylation and secretion of Wnt3a, a mechanism that has been suggested to be conserved for all mammalian Wnt ligands. PORCN mutations in humans cause Focal Dermal Hypoplasia (FDH), a disorder causing developmental defects in heterozygous females and embryonic lethality in hemizygous males. In this study, Porcn mutant mouse embryonic stem (ES) cells were used to analyze the role of Porcn in mammalian embryonic development. In vitro, we show an exclusive requirement for Porcn in Wnt secreting cells and further, that any of the four Porcn isoforms is sufficient to allow for the secretion of functional Wnt3a. Embryos generated by aggregation of Porcn mutant ES cells with wildtype embryos fail to complete gastrulation in vivo, but remain in an epiblast-like state, similar to Wnt3 and Gpr177/Wls mutants. Consistent with this phenotype, in vitro differentiated mutant ES cells fail to generate endoderm and mesoderm derivatives. Taken together, these data confirm the importance of Porcn for Wnt secretion and gastrulation and suggest that disruption of early development underlies the male lethality of human PORCN mutants.

  13. Reciprocal requirements for Eda/Edar/NF-κB and Wnt/β-catenin signaling pathways in hair follicle induction

    PubMed Central

    Zhang, Yuhang; Tomann, Philip; Andl, Thomas; Gallant, Natalie M.; Huelsken, Joerg; Jerchow, Boris; Birchmeier, Walter; Paus, Ralf; Piccolo, Stefano; Mikkola, Marja L.; Morrisey, Edward E.; Overbeek, Paul A.; Scheidereit, Claus; Millar, Sarah E.; Schmidt-Ullrich, Ruth

    2009-01-01

    SUMMARY Wnt/β-catenin and NF-κB signaling mechanisms provide central controls in development and disease, but how these pathways intersect is unclear. Using hair follicle induction as a model system, we show that patterning of dermal Wnt/β-catenin signaling requires epithelial β-catenin activity. We find that Wnt/β-catenin signaling is absolutely required for NF-κB activation, and that Edar is a direct Wnt target gene. Wnt/β-catenin signaling is initially activated independently of Eda/Edar/NF-κB activity in primary hair follicle primordia. However, Eda/Edar/NF-κB signaling is required to refine the pattern of Wnt/β-catenin activity, and to maintain this activity at later stages of placode development. We show that maintenance of localized expression of Wnt10b and Wnt10a requires NF-κB signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-κB target. These data reveal a complex interplay and inter-dependence of Wnt/β-catenin and Eda/Edar/NF-κB signaling pathways in initiation and maintenance of primary hair follicle placodes. PMID:19619491

  14. Optogenetic stimulation of the auditory pathway

    PubMed Central

    Hernandez, Victor H.; Gehrt, Anna; Reuter, Kirsten; Jing, Zhizi; Jeschke, Marcus; Mendoza Schulz, Alejandro; Hoch, Gerhard; Bartels, Matthias; Vogt, Gerhard; Garnham, Carolyn W.; Yawo, Hiromu; Fukazawa, Yugo; Augustine, George J.; Bamberg, Ernst; Kügler, Sebastian; Salditt, Tim; de Hoz, Livia; Strenzke, Nicola; Moser, Tobias

    2014-01-01

    Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics. PMID:24509078

  15. Glial Cell Contributions to Auditory Brainstem Development

    PubMed Central

    Cramer, Karina S.; Rubel, Edwin W

    2016-01-01

    Glial cells, previously thought to have generally supporting roles in the central nervous system, are emerging as essential contributors to multiple aspects of neuronal circuit function and development. This review focuses on the contributions of glial cells to the development of auditory pathways in the brainstem. These pathways display specialized synapses and an unusually high degree of precision in circuitry that enables sound source localization. The development of these pathways thus requires highly coordinated molecular and cellular mechanisms. Several classes of glial cells, including astrocytes, oligodendrocytes and microglia, have now been explored in these circuits in both avian and mammalian brainstems. Distinct populations of astrocytes are found over the course of auditory brainstem maturation. Early appearing astrocytes are associated with spatial compartments in the avian auditory brainstem. Factors from late appearing astrocytes promote synaptogenesis and dendritic maturation, and astrocytes remain integral parts of specialized auditory synapses. Oligodendrocytes play a unique role in both birds and mammals in highly regulated myelination essential for proper timing to decipher interaural cues. Microglia arise early in brainstem development and may contribute to maturation of auditory pathways. Together these studies demonstrate the importance of non-neuronal cells in the assembly of specialized auditory brainstem circuits. PMID:27818624

  16. Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction.

    PubMed

    Prado, M A; Evans-Bain, B; Dickerson, I M

    2002-08-01

    The calcitonin-gene-related peptide (CGRP) receptor component protein (RCP) is a 148-amino-acid intracellular protein that is required for G-protein-coupled signal transduction at receptors for the neuropeptide CGRP. RCP works in conjunction with two other proteins to constitute a functional CGRP receptor: calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein 1 (RAMP1). CRLR has the stereotypical seven-transmembrane topology of a G-protein-coupled receptor; it requires RAMP1 for trafficking to the cell surface and for ligand specificity, and requires RCP for coupling to the cellular signal transduction pathway. We have made cell lines that expressed an antisense construct of RCP and determined that CGRP-mediated signal transduction was reduced, while CGRP binding was unaffected. Furthermore, signalling at two other endogenous G-protein-coupled receptors was unaffected, suggesting that RCP was specific for a limited subset of receptors.

  17. Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border.

    PubMed

    Schille, Carolin; Bayerlová, Michaela; Bleckmann, Annalen; Schambony, Alexandra

    2016-09-01

    The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction.

  18. Phonetic invariance in the human auditory cortex.

    PubMed

    Aulanko, R; Hari, R; Lounasmaa, O V; Näätänen, R; Sams, M

    1993-09-30

    Neuromagnetic signals evoked by synthesized syllables (/bae/ and /gae/) were recorded over the left auditory cortex of healthy humans. The fundamental frequencies of the syllables varied as if the same speaker had pronounced them at 16 different pitches. Specific mismatch responses to infrequent syllables among frequent syllables of the other type indicated that phonetically invariant information had been extracted at the level of the auditory cortex from the extensive irrelevant pitch variation. Such a detection mechanism is necessary for perceiving speech sounds in natural situations with a great deal of acoustic variation present.

  19. Auditory neuroscience: Development, transduction, and integration

    PubMed Central

    Hudspeth, A. J.; Konishi, Masakazu

    2000-01-01

    Hearing underlies our ability to locate sound sources in the environment, our appreciation of music, and our ability to communicate. Participants in the National Academy of Sciences colloquium on Auditory Neuroscience: Development, Transduction, and Integration presented research results bearing on four key issues in auditory research. How does the complex inner ear develop? How does the cochlea transduce sounds into electrical signals? How does the brain's ability to compute the location of a sound source develop? How does the forebrain analyze complex sounds, particularly species-specific communications? This article provides an introduction to the papers stemming from the meeting. PMID:11050196

  20. GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents.

    PubMed

    Ye, Jianping; Hao, Zheng; Mumphrey, Michael B; Townsend, R Leigh; Patterson, Laurel M; Stylopoulos, Nicholas; Münzberg, Heike; Morrison, Christopher D; Drucker, Daniel J; Berthoud, Hans-Rudolf

    2014-03-01

    Exaggerated GLP-1 and PYY secretion is thought to be a major mechanism in the reduced food intake and body weight after Roux-en-Y gastric bypass surgery. Here, we use complementary pharmacological and genetic loss-of-function approaches to test the role of increased signaling by these gut hormones in high-fat diet-induced obese rodents. Chronic brain infusion of a supramaximal dose of the selective GLP-1 receptor antagonist exendin-9-39 into the lateral cerebral ventricle significantly increased food intake and body weight in both RYGB and sham-operated rats, suggesting that, while contributing to the physiological control of food intake and body weight, central GLP-1 receptor signaling tone is not the critical mechanism uniquely responsible for the body weight-lowering effects of RYGB. Central infusion of the selective Y2R-antagonist BIIE0246 had no effect in either group, suggesting that it is not critical for the effects of RYGB on body weight under the conditions tested. In a recently established mouse model of RYGB that closely mimics surgery and weight loss dynamics in humans, obese GLP-1R-deficient mice lost the same amount of body weight and fat mass and maintained similarly lower body weight compared with wild-type mice. Together, the results surprisingly provide no support for important individual roles of either gut hormone in the specific mechanisms by which RYGB rats settle at a lower body weight. It is likely that the beneficial effects of bariatric surgeries are expressed through complex mechanisms that require combination approaches for their identification.

  1. Crucial requirement of ERK/MAPK signaling in respiratory tract development.

    PubMed

    Boucherat, Olivier; Nadeau, Valérie; Bérubé-Simard, Félix-Antoine; Charron, Jean; Jeannotte, Lucie

    2014-08-01

    The mammalian genome contains two ERK/MAP kinase genes, Mek1 and Mek2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation. In order to define the function of the ERK/MAPK pathway in the lung development in mice, we performed tissue-specific deletions of Mek1 function on a Mek2 null background. Inactivation of both Mek genes in mesenchyme resulted in several phenotypes, including giant omphalocele, kyphosis, pulmonary hypoplasia, defective tracheal cartilage and death at birth. The absence of tracheal cartilage rings establishes the crucial role of intracellular signaling molecules in tracheal chondrogenesis and provides a putative mouse model for tracheomalacia. In vitro, the loss of Mek function in lung mesenchyme did not interfere with lung growth and branching, suggesting that both the reduced intrathoracic space due to the dysmorphic rib cage and the omphalocele impaired lung development in vivo. Conversely, Mek mutation in the respiratory epithelium caused lung agenesis, a phenotype resulting from the direct impact of the ERK/MAPK pathway on cell proliferation and survival. No tracheal epithelial cell differentiation occurred and no SOX2-positive progenitor cells were detected in mutants, implying a role for the ERK/MAPK pathway in trachea progenitor cell maintenance and differentiation. Moreover, these anomalies were phenocopied when the Erk1 and Erk2 genes were mutated in airway epithelium. Thus, the ERK/MAPK pathway is required for the integration of mesenchymal and epithelial signals essential for the development of the entire respiratory tract. © 2014. Published by The Company of Biologists Ltd.

  2. GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents

    PubMed Central