Ventral Cochlear Nucleus

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Donata Oertel - One of the best experts on this subject based on the ideXlab platform.

  • the Ventral Cochlear Nucleus
    2020
    Co-Authors: Donata Oertel, Xiaojie Cao
    Abstract:

    Synopsis Acoustic information is brought to the brain from the cochlea through the auditory nerve. The review summarizes what has been learned about how neurons in the Ventral Cochlear Nucleus extract different facets of acoustic information and how it convey them along parallel pathways.

  • the multiple functions of t stellate multipolar chopper cells in the Ventral Cochlear Nucleus
    Hearing Research, 2011
    Co-Authors: Donata Oertel, Michael J Ferragamo, Xiaojie Cao, Samantha Wright, Ramazan Bal
    Abstract:

    Acoustic information is brought to the brain by auditory nerve fibers, all of which terminate in the Cochlear nuclei, and is passed up the auditory pathway through the principal cells of the Cochlear nuclei. A population of neurons variously known as T stellate, type I multipolar, planar multipolar, or chopper cells forms one of the major ascending auditory pathways through the brainstem. T Stellate cells are sharply tuned; as a population they encode the spectrum of sounds. In these neurons, phasic excitation from the auditory nerve is made more tonic by feedforward excitation, coactivation of inhibitory with excitatory inputs, relatively large excitatory currents through NMDA receptors, and relatively little synaptic depression. The mechanisms that make firing tonic also obscure the fine structure of sounds that is represented in the excitatory inputs from the auditory nerve and account for the characteristic chopping response patterns with which T stellate cells respond to tones. In contrast with other principal cells of the Ventral Cochlear Nucleus (VCN), T stellate cells lack a low-voltage-activated potassium conductance and are therefore sensitive to small, steady, neuromodulating currents. The presence of cholinergic, serotonergic and noradrenergic receptors allows the excitability of these cells to be modulated by medial olivoCochlear efferent neurons and by neuronal circuits associated with arousal. T Stellate cells deliver acoustic information to the ipsilateral dorsal Cochlear Nucleus (DCN), Ventral Nucleus of the trapezoid body (VNTB), periolivary regions around the lateral superior olivary Nucleus (LSO), and to the contralateral Ventral lemniscal nuclei (VNLL) and inferior colliculus (IC). It is likely that T stellate cells participate in feedback loops through both medial and lateral olivoCochlear efferent neurons and they may be a source of ipsilateral excitation of the LSO.

  • the magnitudes of hyperpolarization activated and low voltage activated potassium currents co vary in neurons of the Ventral Cochlear Nucleus
    Journal of Neurophysiology, 2011
    Co-Authors: Xiaojie Cao, Donata Oertel
    Abstract:

    In the Ventral Cochlear Nucleus (VCN), neurons have hyperpolarization-activated conductances, which in some cells are enormous, that contribute to the ability of neurons to convey acoustic informat...

  • voltage sensitive conductances of bushy cells of the mammalian Ventral Cochlear Nucleus
    Journal of Neurophysiology, 2007
    Co-Authors: Xiaojie Cao, Shalini Shatadal, Donata Oertel
    Abstract:

    Bushy cells in the Ventral Cochlear Nucleus convey firing of auditory nerve fibers to neurons in the superior olivary complex that compare the timing and intensity of sounds at the two ears and ena...

  • rate thresholds determine the precision of temporal integration in principal cells of the Ventral Cochlear Nucleus
    Hearing Research, 2006
    Co-Authors: Matthew J Mcginley, Donata Oertel
    Abstract:

    The three types of principal cells of the Ventral Cochlear Nucleus (VCN), bushy, octopus, and T stellate, differ in the detection of coincidence among synaptic inputs. To explore the role of the action-potential-generation mechanism in the detection of coincident inputs, we examined responses to depolarizing currents that increased at varying rates. To fire an action potential, bushy cells, likely of the globular subtype, had to be depolarized faster than 4.8+/-2.8 mV/ms, octopus cells faster than 9.5+/-3.6 mV/ms, and T stellate cells fired irrespective of the rate of depolarization. The threshold rate of depolarization permitted definition of a time window over which depolarization could contribute to generating action potentials. This integration window differed between cell types. It was 5.3+/-1.8 ms for bushy cells and 1.4+/-0.3 ms for octopus cells. T Stellate cells fired action potentials in response to even slow depolarizations, showing that their integration window was unlimited so that temporal summation in these cells is limited by the time course of synaptic potentials. The rate of depolarization threshold in octopus and bushy cells was decreased by alpha-dendrotoxin while T stellate cells were largely insensitive to alpha-dendrotoxin indicating that low-voltage-activated K+ conductances (gKL) are important determinants of the integration window.

Susan E. Shore - One of the best experts on this subject based on the ideXlab platform.

  • Ventral Cochlear Nucleus bushy cells encode hyperacusis in guinea pigs
    Scientific Reports, 2020
    Co-Authors: David T Martel, Susan E. Shore
    Abstract:

    Psychophysical studies characterize hyperacusis as increased loudness growth over a wide-frequency range, decreased tolerance to loud sounds and reduced behavioral reaction time latencies to high-intensity sounds. While commonly associated with hearing loss, hyperacusis can also occur without hearing loss, implicating the central nervous system in the generation of hyperacusis. Previous studies suggest that Ventral Cochlear Nucleus bushy cells may be putative neural contributors to hyperacusis. Compared to other Ventral Cochlear Nucleus output neurons, bushy cells show high firing rates as well as lower and less variable first-spike latencies at suprathreshold intensities. Following Cochlear damage, bushy cells show increased spontaneous firing rates across a wide-frequency range, suggesting that they might also show increased sound-evoked responses and reduced latencies to higher-intensity sounds. However, no studies have examined bushy cells in relationship to hyperacusis. Herein, we test the hypothesis that bushy cells may contribute to the neural basis of hyperacusis by employing noise-overexposure and single-unit electrophysiology. We find that bushy cells exhibit hyperacusis-like neural firing patterns, which are comprised of enhanced sound-driven firing rates, reduced first-spike latencies and wideband increases in excitability.

  • multisensory activation of Ventral Cochlear Nucleus d stellate cells modulates dorsal Cochlear Nucleus principal cell spatial coding
    The Journal of Physiology, 2018
    Co-Authors: Susan E. Shore
    Abstract:

    Key points Dorsal Cochlear Nucleus fusiform cells receive spectrally relevant auditory input for sound localization. Fusiform cells integrate auditory with other multisensory inputs. Here we elucidate how somatosensory and vestibular stimulation modify the fusiform cell spatial code through activation of an inhibitory interneuron: the Ventral Cochlear Nucleus D-stellate cell. These results suggests that multisensory cues interact early in an ascending sensory pathway to serve an essential function. Abstract In the Cochlear Nucleus (CN), the first central site for coding sound location, numerous multisensory projections and their modulatory effects have been reported. However, multisensory influences on sound location processing in the CN remain unknown. The principal output neurons of the dorsal CN, fusiform cells, encode spatial information through frequency-selective responses to direction-dependent spectral features. Here, single-unit recordings from the guinea pig CN revealed transient alterations by somatosensory and vestibular stimulation in fusiform cell spatial coding. Changes in fusiform cell spectral sensitivity correlated with multisensory modulation of Ventral CN D-stellate cell responses, which provide direct, wideband inhibition to fusiform cells. These results suggest that multisensory inputs contribute to spatial coding in DCN fusiform cells via an inhibitory interneuron, the D-stellate cell. This early multisensory integration circuit likely confers important consequences on perceptual organization downstream.

  • multisensory integration enhances temporal coding in Ventral Cochlear Nucleus bushy cells
    The Journal of Neuroscience, 2018
    Co-Authors: Amarins N Heeringa, Susan E. Shore
    Abstract:

    Temporal coding of auditory stimuli is critical for understanding communication signals. The bushy cell, a major output neuron of the Ventral Cochlear Nucleus, can "phase-lock" precisely to pure tones and the envelopes of complex stimuli. Bushy cells are also putative recipients of brainstem somatosensory projections and could therefore play a role in perception of communication signals because multisensory integration is required for such complex sound processing. Here, we examine the role of multisensory integration in temporal coding in bushy cells by activating the spinal trigeminal Nucleus (Sp5) while recording responses from bushy cells. In normal-hearing guinea pigs of either sex, bushy cell single unit responses to amplitude-modulated (AM) broadband noise were compared with those in the presence of preceding Sp5 electrical stimulation (i.e., bimodal stimuli). Responses to the AM stimuli were also compared with those obtained 45 min after the bimodal stimulation. Bimodal auditory-Sp5 stimulation resulted in enhanced envelope coding for low modulation frequencies, which persisted for up to 45 min. AM detection thresholds were significantly improved 45 min after bimodal auditory-Sp5 stimulation, but not during bimodal auditory-Sp5 stimulation. Anterograde labeling of Sp5 projections was found within the dendritic fields of bushy cells and their inhibitory interneurons, D-stellate cells. Therefore, enhanced AM responses and improved AM sensitivity of bushy cells were likely facilitated by Sp5 neurons through monosynaptic excitatory projections and indirect inhibitory projections. These somatosensory projections may be involved in the improved perception of communication stimuli with multisensory stimulation, consistent with psychophysical studies in humans.SIGNIFICANCE STATEMENT Multisensory integration is crucial for sensory coding because it improves sensitivity to unimodal stimuli and enhances responses to external stimuli. Although multisensory integration has typically been described in the cerebral cortex, the Cochlear Nucleus in the brainstem is also innervated by multiple sensory systems, including the somatosensory and auditory systems. Here, we showed that convergence of these two sensory systems in the Cochlear Nucleus results in improved temporal coding in bushy cells, principal output neurons that send projections to higher auditory structures. The improved temporal coding instilled by bimodal auditory-Sp5 stimulation may be important in priming the neurons for coding biologically relevant sounds such as communication signals.

  • Ventral Cochlear Nucleus responses to contralateral sound are mediated by commissural and olivoCochlear pathways
    Journal of Neurophysiology, 2009
    Co-Authors: Sanford C Bledsoe, Seth Koehler, Debara L Tucci, Jianxun Zhou, Colleen Le G Prell, Susan E. Shore
    Abstract:

    In the normal guinea pig, contralateral sound inhibits more than a third of Ventral Cochlear Nucleus (VCN) neurons but excites <4% of these neurons. However, unilateral conductive hearing loss (CHL) and Cochlear ablation (CA) result in a major enhancement of contralateral excitation. The response properties of the contralateral excitation produced by CHL and CA are similar, suggesting similar pathways are involved for both types of hearing loss. Here we used the neurotoxin melittin to test the hypothesis that this “compensatory” contralateral excitation is mediated either by direct glutamatergic CN-commissural projections or by cholinergic neurons of the olivoCochlear bundle (OCB) that send collaterals to the VCN. Unit responses were recorded from the left VCN of anesthetized, unilaterally deafened guinea pigs (CHL via ossicular disruption, or CA via mechanical destruction). Neural responses were obtained with 16-channel electrodes to enable simultaneous data collection from a large number of single- and multiunits in response to ipsi- and contralateral tone burst and noise stimuli. Lesions of each pathway had differential effects on the contralateral excitation. We conclude that contralateral excitation has a fast and a slow component. The fast excitation is likely mediated by glutamatergic neurons located in medial regions of VCN that send their commissural axons to the other CN via the dorsal/intermediate acoustic striae. The slow component is likely mediated by the OCB collateral projections to the CN. Commissural neurons that leave the CN via the trapezoid body are an additional source of fast, contralateral excitation.

  • responses of Ventral Cochlear Nucleus neurons to contralateral sound after conductive hearing loss
    Journal of Neurophysiology, 2005
    Co-Authors: Christian J Sumner, Debara L Tucci, Susan E. Shore
    Abstract:

    Conductive hearing loss (CHL) is an attenuation of signals stimulating the cochlea, without damage to the auditory end organ. It can cause central auditory processing deficits that outlast the CHL itself. Measures of oxidative metabolism show a decrease in activity of nuclei receiving input originating at the affected ear but, surprisingly, an increase in the activity of second-order neurons of the opposite ear. In normal hearing animals, contralateral sound produces an inhibitory response to broadband noise in approximately one third of Ventral Cochlear Nucleus (VCN) neurons. Excitatory responses also occur but are very rare. We looked for changes in the binaural properties of neurons in the VCN of guinea pigs at intervals immediately, 1 day, 1 wk, and 2 wk after the induction of a unilateral CHL by ossicular disruption. CHL was always induced in the ear ipsilateral to the VCN from which recordings were made. The main observations were as follows: 1) ipsilateral excitatory thresholds were raised by at least 40 dB; 2) contralateral inhibitory responses showed a small but statistically significant immediate decrease followed by an increase, returning to normal by 14 days; and 3) there was a large increase in the proportion of units with excitatory responses to contralateral BBN. The increase was immediate and lasting. The latencies of the excitatory responses were at least 6 ms, consistent with activation by a path involving several synapses and inconsistent with cross talk. The latencies and rate-level functions of contralateral excitation were similar to those seen occasionally in normal hearing animals, suggesting an upregulation of an existing pathway. In conclusion, contralateral excitatory inputs to the VCN exist, which are not normally effective, and can compensate rapidly for large changes in afferent input.

Ian M. Winter - One of the best experts on this subject based on the ideXlab platform.

  • dual coding of frequency modulation in the Ventral Cochlear Nucleus
    The Journal of Neuroscience, 2018
    Co-Authors: Arkadiusz Stasiak, Nihaad Paraouty, Christian Lorenzi, Leo Varnet, Ian M. Winter
    Abstract:

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

  • modelling firing regularity in the Ventral Cochlear Nucleus mechanisms and effects of stimulus level and synaptopathy
    bioRxiv, 2017
    Co-Authors: Dan F M Goodman, Ian M. Winter, Agnes C Leger, Alain De Cheveigne, Christian Lorenzi
    Abstract:

    The auditory system processes temporal information at multiple scales, and disruptions to this temporal processing may lead to deficits in auditory tasks such as detecting and discriminating sounds in a noisy environment. Here, a modelling approach is used to study the temporal regularity of firing by chopper cells in the Ventral Cochlear Nucleus, in both the normal and impaired auditory system. Chopper cells, which have a strikingly regular firing response, divide into two classes, sustained and transient, based on the time course of this regularity. Several hypotheses have been proposed to explain the behaviour of chopper cells, and the difference between sustained and transient cells in particular. However, there is no conclusive evidence so far. Here, a reduced mathematical model is developed and used to compare and test a wide range of hypotheses with a limited number of parameters. Simulation results show a continuum of cell types and behaviours: chopper-like behaviour arises for a wide range of parameters, suggesting that multiple mechanisms may underlie this behaviour. The model accounts for systematic trends in regularity as a function of stimulus level that have previously only been reported anecdotally. Finally, the model is used to predict the effects of a reduction in the number of auditory nerve fibres (deafferentation due to, for example, Cochlear synaptopathy). An interactive version of this paper in which all the model parameters can be changed is available online.

  • neural segregation of concurrent speech effects of background noise and reverberation on auditory scene analysis in the Ventral Cochlear Nucleus
    Advances in Experimental Medicine and Biology, 2016
    Co-Authors: Mark Sayles, Arkadiusz Stasiak, Ian M. Winter
    Abstract:

    Concurrent complex sounds (e.g., two voices speaking at once) are perceptually disentangled into separate “auditory objects”. This neural processing often occurs in the presence of acoustic-signal distortions from noise and reverberation (e.g., in a busy restaurant). A difference in periodicity between sounds is a strong segregation cue under quiet, anechoic conditions. However, noise and reverberation exert differential effects on speech intelligibility under “cocktail-party” listening conditions. Previous neurophysiological studies have concentrated on understanding auditory scene analysis under ideal listening conditions. Here, we examine the effects of noise and reverberation on periodicity-based neural segregation of concurrent vowels /a/ and /i/, in the responses of single units in the guinea-pig Ventral Cochlear Nucleus (VCN): the first processing station of the auditory brain stem. In line with human psychoacoustic data, we find reverberation significantly impairs segregation when vowels have an intonated pitch contour, but not when they are spoken on a monotone. In contrast, noise impairs segregation independent of intonation pattern. These results are informative for models of speech processing under ecologically valid listening conditions, where noise and reverberation abound.

  • Response to best-frequency tone bursts in the Ventral Cochlear Nucleus is governed by ordered inter-spike interval statistics
    Hearing research, 2014
    Co-Authors: Matthew Wright, Ian M. Winter, Jonathan J. Forster, Stefan Bleeck
    Abstract:

    The spike trains generated by short constant-amplitude constant-frequency tone bursts in the Ventral Cochlear Nucleus of the anaesthetised guinea pig are examined. Spikes are grouped according to the order in which they occur following the onset of the stimulus. It is found that successive inter-spike intervals have low statistical dependence according to information-theoretic measures. This is in contrast to previous observations with long-duration tone bursts in the cat dorsal and posteroVentral Cochlear nuclei and lateral superior olive, where it was found that long intervals tended to be followed by shorter ones and vice versa. The interval distributions can also be reasonably modelled by a shifted Gamma distribution parameterised by the dead-time and the mean and coefficient of variation of the dead-time corrected ISI distribution. Knowledge of those three parameters for each interval is sufficient to determine the peri-stimulus time histogram and the regularity measures used to classify these neurons.

  • enhancement of forward suppression begins in the Ventral Cochlear Nucleus
    Brain Research, 2014
    Co-Authors: Neil J Ingham, Stefan Bleeck, Naoya Itatani, Ian M. Winter
    Abstract:

    A neuron׳s response to a sound can be suppressed by the presentation of a preceding sound. It has been suggested that this suppression is a direct correlate of the psychophysical phenomenon of forward masking, however, forward suppression, as measured in the responses of the auditory nerve, was insufficient to account for behavioural performance. In contrast the neural suppression seen in the inferior colliculus and auditory cortex was much closer to psychophysical performance. In anaesthetised guinea-pigs, using a physiological two-interval forced-choice threshold tracking algorithm to estimate suppressed (masked) thresholds, we examine whether the enhancement of suppression can occur at an earlier stage of the auditory pathway, the Ventral Cochlear Nucleus (VCN). We also compare these responses with the responses from the central Nucleus of the inferior colliculus (ICc) using the same preparation. In both nuclei, onset-type neurons showed the greatest amounts of suppression (16.9-33.5dB) and, in the VCN, these recovered with the fastest time constants (14.1-19.9ms). Neurons with sustained discharge demonstrated reduced masking (8.9-12.1dB) and recovery time constants of 27.2-55.6ms. In the VCN the decrease in growth of suppression with increasing suppressor level was largest for chopper units and smallest for onset-type units. The threshold elevations recorded for most unit types are insufficient to account for the magnitude of forward masking as measured behaviourally, however, onset responders, in both the Cochlear Nucleus and inferior colliculus demonstrate a wide dynamic range of suppression, similar to that observed in human psychophysics.

Antonio G Paolini - One of the best experts on this subject based on the ideXlab platform.

  • inferior colliculus responses to dual site intralamina stimulation in the Ventral Cochlear Nucleus
    The Journal of Comparative Neurology, 2010
    Co-Authors: Mohit N Shivdasani, Stefan J Mauger, Rebecca E Argent, Graeme D Rathbone, Antonio G Paolini
    Abstract:

    A major limitation of the present auditory brainstem implant (ABI) is its inability to access the tonotopic organization of the Ventral Cochlear Nucleus (VCN).

  • neural timing inhibition and the nature of stellate cell interaction in the Ventral Cochlear Nucleus
    Hearing Research, 2006
    Co-Authors: Karina Needham, Antonio G Paolini
    Abstract:

    The Ventral Cochlear Nucleus (VCN) stellate cell population comprises two clusters: narrowly-tuned, excitatory T stellate neurons, and D stellate neurons, a broadly-tuned population of inhibitory cells. These neurons respond to best frequency (BF) tone bursts in a chopper or onset manner, respectively. Through extensive local and commissural projections the D stellate population provides a source of fast inhibitory input to both intrinsic and contralateral T stellate neurons. Whilst the nature of interactions between intrinsic stellate populations is difficult to examine, our previous intracellular investigations of the commissural pathway have provided a means by which to study this relationship in the in vivo preparation. It is the aim of this paper to both review and extend our understanding of the link between stellate populations and their involvement in the commissural pathway by presenting an overview of the results attained in our recently expanded study. The sample of 17 intracellular and 34 extracellular onset chopper (O(C)) and late/ideal (On(L)/On(I)) neurons revealed antidromic activity in 31.4% of neurons following contralateral stimulation, providing physiological evidence that On(L)/On(I) neurons also contribute projections to the commissural connection. Alternatively, 64.7% of the 34 intracellularly-recorded chopper neurons displayed fast, monosynaptic inhibitory potentials. This commissural input was found to influence the timing of neural activity in chopper neurons, providing insight into the relationship that exists between T and D stellate neurons.

  • balanced inhibition and excitation underlies spike firing regularity in Ventral Cochlear Nucleus chopper neurons
    European Journal of Neuroscience, 2005
    Co-Authors: Antonio G Paolini, Janine C Clarey, Karina Needham, Graeme M Clark
    Abstract:

    Ventral Cochlear Nucleus stellate cells respond to characteristic frequency (CF) tones with sustained (C(S)), transient (C(T)) or onset chopping (O(C)) activity. The mechanisms underlying these different response patterns are not fully understood, and the present study used in vivo intracellular recordings (n = 42) in urethane-anaesthetized rats to examine the possible influence of inhibition on action potential regularity. Hyperpolarization following the offset of a CF tone burst was used as a measure of on-CF inhibition. A cluster analysis based on several membrane potential features, including on-CF inhibition, discriminated three groups in addition to the C(S) response type - two types of C(T) responses and the O(C) type. The different patterns of firing regularity exhibited by C(S/T) neurons reflected different thresholds or degrees of overlap between these cells' narrowly tuned excitatory and inhibitory inputs. C(T) cells with closely matched inhibitory and excitatory response areas showed substantial on-CF inhibition and the greatest decline in firing regularity during a CF tone, whereas those with a mismatch between their response areas showed lateral inhibition and a less marked decline in firing regularity. The presence of inhibition in C(S) neurons did not alter their firing regularity, possibly because of the lower threshold for excitation compared with inhibition. The latency, duration and frequency extent of sustained hyperpolarization in C(S/T) cells is inconsistent with the response properties of O(C) neurons, suggesting that another source(s) of inhibition influences firing regularity, and presumably response magnitude, in these neurons.

  • Ventral Cochlear Nucleus coding of voice onset time in naturally spoken syllables
    Hearing Research, 2004
    Co-Authors: Janine C Clarey, Antonio G Paolini, Graeme M Clark, David B Grayden, Anthony N Burkitt
    Abstract:

    These experiments examined the coding of the voice onset time (VOT) of six naturally spoken syllables, presented at a number of intensities, by Ventral Cochlear Nucleus (VCN) neurons in rats anesthetized with urethane. VOT is one of the cues for the identification of a stop consonant, and is defined by the interval between stop release and the first glottal pulse that marks the onset of voicing associated with a vowel. The syllables presented (/bot/, /dot/, /got/, /pot/, /tot/, /kot/) each had a different VOT, ranging between 10 and 108 ms. Extracellular recordings were made from single neurons (N=202) with a wide range of best frequencies (BFs; 0.66-10 kHz) that represented the major VCN response types - primary-like (67.8% of sample), chopper (19.8%), and onset (12.4%) neurons. The different VOTs of the syllables were accurately reflected in sharp, precisely timed, and statistically significant changes in average discharge rate in all cell types, as well as the entire VCN sample. The prominence of the response to stop release and voice onset, and the level of activity prior to the VOT, were influenced by syllable intensity and the spectrum of stop release, as well as cell BF and type. Our results suggest that the responses of VCN cells with BFs above the first formant frequency are dominated by their sensitivity to the onsets of broadband events in speech, and allows them to convey accurate information about a syllable's VOT.

  • intracellular responses of onset chopper neurons in the Ventral Cochlear Nucleus to tones evidence for dual component processing
    Journal of Neurophysiology, 1999
    Co-Authors: Antonio G Paolini, Graeme M Clark
    Abstract:

    Intracellular responses of onset chopper neurons in the Ventral Cochlear Nucleus to tones: evidence for dual-component processing. The Ventral Cochlear Nucleus (VCN) contains a heterogeneous collec...

Shankai Yin - One of the best experts on this subject based on the ideXlab platform.

  • nad attenuates bilirubin induced hyperexcitation in the Ventral Cochlear Nucleus by inhibiting excitatory neurotransmission and neuronal excitability
    Frontiers in Cellular Neuroscience, 2017
    Co-Authors: Min Liang, Haibo Shi, Xinlu Yin, Ningying Song, Luyang Wang, Weihai Yin, Shankai Yin
    Abstract:

    Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little is known regarding the roles of NAD+ in neuronal excitation and excitotoxicity associated with many neurodegenerative disorders and diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons in the Ventral Cochlear Nucleus (VCN), which is particularly vulnerable to bilirubin excitotoxicity. We found that NAD+ effectively decreased the size of evoked excitatory postsynaptic currents (eEPSCs), increased paired-pulse ratio (PPR), and reversed the effect of bilirubin on eEPSCs, implicating its inhibitory effects on the presynaptic release probability (Pr). Moreover, NAD+ not only decreased the basal frequency of miniature EPSCs (mEPSCs), but also reversed bilirubin-induced increases in the frequency of mEPSCs without affecting their amplitude under either condition. Furthermore, we found that NAD+ decreased the frequency of spontaneous firing of VCN neurons as well as bilirubin-induced increases in firing frequency. Whole-cell current-clamp recordings showed that NAD+ could directly decrease the intrinsic excitability of VCN neurons in the presence of synaptic blockers, suggesting NAD+ exerts its actions in both presynaptic and postsynaptic loci. Consistent with these observations, we found that the latency of the first postsynaptic spike triggered by high-frequency train stimulation of presynaptic afferents (i.e. the auditory nerve) was prolonged by NAD+. These results collectively indicate that NAD+ suppresses presynaptic transmitter release and postsynaptic excitability, jointly weakening excitatory neurotransmission. Our findings provide a basis for the exploration of NAD+ for the prevention and treatment of bilirubin encephalopathy and excitotoxicity associated with other neurological disorders.

  • riluzole is a promising pharmacological inhibitor of bilirubin induced excitotoxicity in the Ventral Cochlear Nucleus
    CNS Neuroscience & Therapeutics, 2015
    Co-Authors: Guoying Han, Haibo Shi, Jiping Wang, Xinlu Yin, Shankai Yin
    Abstract:

    Summary Background and purpose Bilirubin encephalopathy as a result of hyperbilirubinemia is a devastating neurological disorder that occurs mostly in the neonatal period. To date, no effective drug treatment is available. Glutamate-mediated excitotoxicity is likely an important factor causing bilirubin encephalopathy. Thus, drugs suppressing the overrelease of glutamate may protect the brain against bilirubin excitotoxicity. Riluzole is a prescription drug known for its antiglutamatergic function. This study was conducted in the rat's Ventral Cochlear Nucleus, a structure highly sensitive to bilirubin toxicity, to find whether riluzole can be used to inhibit bilirubin toxicity. Experimental approach Electrophysiology changes were detected by perforated patch clamp technique. Calcium imaging using Rhod-2-AM as an indicator was used to study the intracellular calcium. Cell apoptosis and necrosis were measured by PI/Hoechst staining. Key results In the absence of bilirubin, riluzole effectively decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and suppressed neuronal firing but did not change the amplitude of sEPSC and glutamate-activated currents (IGlu). Moreover, riluzole inhibited bilirubin-induced increases in the frequency of sEPSC and neuronal firing. Riluzole could prevent the bilirubin-induced increase in intracellular calcium, mediated by AMPA and NMDA receptors. Furthermore, riluzole significantly reduced bilirubin-induced cell death. Conclusions and implications These data suggest that riluzole can protect neurons in the Ventral Cochlear Nucleus from bilirubin-induced hyperexcitation and excitotoxicity through reducing presynaptic glutamate release.

  • minocycline cannot protect neurons against bilirubin induced hyperexcitation in the Ventral Cochlear Nucleus
    Experimental Neurology, 2012
    Co-Authors: Haibo Shi, Ningying Song, Shankai Yin
    Abstract:

    Abstract Excitotoxicity has been suggested to play an important role in many central nervous system diseases, particularly in bilirubin encephalopathy. Minocycline treatment has been proposed to be one of the most promising potential therapies for excitotoxicity-induced neurological disorders. However, some key questions, such as the electrophysiological effect of minocycline on neuronal excitability and hyperexcitation in pathological conditions, require clarification. In this study, using patch-clamp techniques, we showed that bilirubin increased the frequency of both spontaneous excitatory postsynaptic currents (sEPSCs) and neuronal firing in isolated Ventral Cochlear Nucleus (VCN) neurons at postnatal days 11–14 (P11–14) in rats but it did not affect the amplitude of sEPSCs or glutamate-activated (IGlu) currents. However, minocycline had no effect on sEPSC frequency or IGlu amplitude. Furthermore, minocycline pretreatment did not abolish bilirubin-induced sEPSC potentiation or neuron firing. These data suggest that minocycline does not affect excitatory synaptic transmission or hyperexcitation induced by bilirubin in VCN neurons. From these results, we propose that the neuroprotective efficacy of minocycline, if it can protect neurons against neurotoxicity induced by substances like bilirubin, is mediated by either an alternative mechanism or downstream events post neuronal hyperexcitation. Certainly, additional investigation of the neuroprotective effects of minocycline is required before embarking on further clinical trials.

  • bilirubin facilitates depolarizing gaba glycinergic synaptic transmission in the Ventral Cochlear Nucleus of rats
    European Journal of Pharmacology, 2011
    Co-Authors: Haibo Shi, Ningying Song, Jian Wang, Shankai Yin
    Abstract:

    Abstract Excitotoxicity contributes to bilirubin-induced central nervous system injury; however, the mechanisms involved remain controversial. Previous studies from our lab have demonstrated that in juvenile rats bilirubin faciliates γ-aminobutyric acid (GABA)/glycinergic synaptic transmission through activation of presynaptic protein kinase A (PKA) in isolated neurons of the Ventral Cochlear Nucleus (VCN). However, the descending mechanism and physiological effects of bilirubin-induced potentiation remain unclear. Here, whole-cell recordings show that 3 × 10 − 6  M bilirubin increased the frequency of both spontaneous (sPSCs) and miniature (mPSCs) GABA/glycinergic postsynaptic currents in VCN neurons of postnatal day 12–14 (P12–14) rats. This action was dependent on the concentration and duration of exposure to bilirubin and was only partially suppressed by 10 − 5  M bicuculline. The potentiation effect on mPSCs persisted in a Ca 2+ -free solution, but was fully occluded by pretreatment with 1,2 bis-(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM), an intracellular Ca 2+ chelator. Following pretreatment of the neurons with BAPTA-AM, forskolin, a PKA activator, had no effect on the frequency or amplitude of mPSCs. This suggests that Ca 2+ release from presynaptic stores is part of the descending pathway of PKA activation and is responsible for biliurbin-induced potentiation of cell activity. Using gramicidin-perforated patch recordings, the reversal potential of GABA-evoked currents (E GABA ) was also investigated. The GABA response resulted in depolarization of 12 of 20 recorded VCN neurons from P12–14 rats. Therefore, potentiation of depolarizing GABA/glycinergic transmission by bilirubin may underlie bilirubin excitotoxicity, which may play a role in the hearing impairment observed among hyperbilirubinemic neonates.