Robert E. Wickesberg

Glycinergic Inhibition in the Cochlear Nuclei: Evidence for Tuberculoventral Neurons being Glycinergic

The goal of this article is to review evidence that glycine is the neurotransmitter of inhibitory interneurons in the cochlear nuclei. One group of interneurons for which the evidence is particularly strong is the tuberculoventral neurons (Wickesberg and Oertel,’ 88) in the deep layer of the dorsal cochlear nucleus (DCN). This review will examine how the existing evidence supports the criteria that have been established for the identification of a neurotransmitter (Werman,’ 66). A review of this evidence leads to the conclusion that tuberculoventral neurons are glycinergic. The evidence is weaker that cartwheel cells of the DCN and D stellate cells of the ventral cochlear nucleus (VCN) are also glycinergic.

Rapid inhibition in the cochlear nuclear complex of the chinchilla

This study examined responses to pairs of clicks recorded extracellularly from single units in ventral cochlear nuclei (VCN) of ketamine-anesthetized chinchillas. The response to the trailing click was suppressed for interclick intervals of 1 and 2 ms, but little suppression was observed for an interclick interval of 4 ms. To determine whether any suppression originated in the dorsal cochlear nucleus (DCN), responses to click pairs were recorded before and after injecting lidocaine in the deep layer of the DCN. For 19% of the neurons (7/37), the response to the trailing click increased following the injection, which is consistent with lidocaine reducing delayed inhibition from the DCN. Unexpectedly, for 62% of the units (23/37) the response to the initial click decreased after lidocaine administration. Three units (3/37 or 8%) showed a combination of both responses. For 52% of the units with a decreased response (12/23), the reduction occurred only for loud clicks (> or = 30 dB above threshold), while at intensities 20 dB lower, responses to pairs of clicks were unchanged. No changes in spontaneous rate were observed. Following lidocaine injections, the tuning curves of 7/12 neurons tested had increased thresholds, but only around the characteristic frequency. These results indicate the presence of two rapid inhibitory inputs onto VCN neurons.

Auditory nerve neurotransmitter acts on a kainate receptor: evidence from intracellular recordings in brain slices from mice.

Intracellular recordings from neurons in brain slice preparations of the mouse ventral cochlear nucleus (VCN) were used to examine the actions of excitatory amino acid agonists and antagonists. Synaptic responses to electrical stimulation of the auditory nerve root were partially blocked by kynurenic acid, an antagonist that is specific for glutamate receptors. The antagonists specific for N-methyl-D-aspartate (NMDA), DL-2-amino-5-phosphonovalerate (APV) and Mg2+, did not affect the response, arguing against a role for NMDA receptors at the VIIIth nerve synapse. To test postsynaptic sensitivity to excitatory amino acid agonists, responses to bath applications were measured in VCN neurons while synaptic transmission was blocked by the removal of Ca2+ from the bath or by the addition of tetrodotoxin. Neurons in the VCN were 500-1000 times more sensitive to kainate than to glutamate or aspartate. In the absence of Mg2+, they were also sensitive to NMDA. The responses to kainate and glutamate were increased by the removal of calcium from the bath. These results imply that VCN neurons have both kainate and NMDA receptors and that synaptic transmission between auditory nerve fibers and neurons in the cochlear nuclear complex could be mediated by a substance related to kainate.

Ascending Pathways Through Ventral Nuclei of the Lateral Lemniscus and Their Possible Role in Pattern Recognition in Natural Sounds

In all higher vertebrates, the nuclei of the lateral lemniscus lie interposed between the cochlear nuclei and the inferior colliculi. The integrative roles of these neurons in the largely monaural, ventral nuclei of the lateral lemniscus are not well understood, but they are intriguing. The suggestion has been made that neurons in the ventral nuclei of the lateral lemniscus are involved in pattern recognition. It is, however, difficult to pinpoint the role of a specific small nucleus in such a complex function. The goal of this chapter is to examine what is known about the ventral lemniscal nuclei to yield clues about their possible role in the identification of sounds.

Wiener kernel analysis of responses from anteroventral cochlear nucleus neurons.

Responses to pseudo-random Gaussian white noise, tones and clics were recorded from neurons in the anteroventral cochlear nucleus (AVCN) of barbiturate anesthetized cats. The responses to white noise were used to calculate estimates of the zero-, first- and second-order Wiener kernels for these neurons. The Wiener kernels did contain useful information on the fundamental, DC and second harmonic components of the responses of AVCN neurons to tones, clicks and noise. However, they generally did not provide predictions of the difference tone distortion products found in the peripheral auditory system. Overall, the addition of the second kernel improved a prediction based on the zero- and first-order kernels, but not by very much. If the estimates of the Wiener kernels were not very good, then a second-order prediction could be worse than a first-order one. To produce good estimates of the Wiener kernels, many repetitions of very long Gaussian white noise stimuli are necessary. Therefore the technique does not permit rapid data collection. Further, exposure to long duration high intensity noise can result in acoustic trauma. This damage effects the mechanism that generates the difference tone distortion products, and it can also affect the tuning of the auditory neurons. Thus Wieners nonlinear system identification theory has only limited usefulness in the analysis of the peripheral auditory system.

Artifacts in Wiener Kernels Estimated Using Gaussian White Noise

Wieners nonlinear system identification theory characterizes a system function with a set of kernels of integrals. One method of determining these Wiener kernels is the cross-correlation technique proposed by Lee and Schetzen, which uses Gaussian white noise as the input to the unknown system. Because a test stimulus is only an approximation of infinitely long Gaussian white noise, it is possible that artifacts are generated during the estimation of the kernels. To help identify and characterize these artifacts, Wiener kernel estimates for two simple nonlinear model systems were made using a pseudorandom Gaussian white noise sequence. The results showed that because of the approximation of a Gaussian distribution, artifacts appear in the estimated kernels due to a form of aliasing. These artifacts can be reduced by increasing the sequence length of the input noise.

Ensemble responses of the auditory nerve to normal and whispered stop consonants

Whispered syllables lack many of the frequency and voicing cues of normally voiced speech, but these two acoustically distinct forms of speech are placed into the same linguistic categories. To examine how whispered and voiced speech are encoded in the auditory system, the responses to speech sounds were recorded from 132 single auditory nerve fibers in 20 ketamine anesthetized chinchillas. Stimuli were the naturally produced syllables /da/ and /ta/ presented in whispered and normal voicing. The results for each syllable presented at a fixed intensity were analyzed by pooling the responses from individual auditory nerve fibers across animals to create a global average peri-stimulus time (GAPST) histogram. For each word-initial consonant, the pattern of peaks in the GAPST was the same for both normal and whispered speech. For the vowel the GAPSTs for the whispered speech sounds did not display the synchronization observed in the responses to the voiced syllables. The temporal pattern of the peaks was constant over a 40 dB intensity range, although peak sizes varied. Grouping fibers within different frequency ranges created local averages (LAPST) that revealed the significant contribution of high frequency fibers in the response to the whispered consonants. Responses of individual fibers varied with both the syllable and the voicing. These findings suggest that the encoding of either a whispered or a normal stop consonant results in the same temporal pattern in the ensemble response.

Longitudinal Stiffness Coupling in a 1-Dimensional Model of the Peripheral Ear

A one-dimensional computer model of the peripheral ear was explored using pure-tone inputs. This model was adopted after frequency-domain modeling showed that the differences between one- and two-dimensional models were small. The inner ear representation was the classical mass-spring-damper transmission line. In the time-domain simulations, this classical model was modified to have adjacent elements of the cochlear partition model lightly coupled to each other via springs.

Intrinsic Connections in the Cochlear Nuclear Complex Studied in Vitro and in Vivo

The lateral ventrotubercular tract was described first by Lorente de No (’33,’ 81) in Golgi studies of cat and mouse cochlear nuclei. This tract connects the dorsal (DCN) and the ventral (VCN) cochlear nucleus. The projection from neurons in the deep layer of the DCN to the VCN has been found in bats (Feng and Vater,’ 85), mice (Wickesberg and Oertel,’ 88; Wickesberg et al.,’ 91), cats (Snyder and Leake,’ 88), gerbils (Mu ller,’ 90) and guinea pigs (Saint-Marie et al.,’ 91). Because these neurons project from the tuberculum acusticum (Cajal,’ 09) to the VCN, they have been called tuberculoventral cells (Oertel and Wu,’ 89). This paper reviews the findings of our in vitro studies on the anatomy and physiology of this projection, examines the hypothesis that this intrinsic circuit contributes to the monaural suppression of echoes, and presents preliminary results from in vivo experiments that begin to examine this hypothesis.

The representation of noise vocoded speech in the auditory nerve of the chinchilla: Physiological correlates of the perception of spectrally reduced speech

This study investigated the neural representation of naturally produced and noise vocoded speech signals in the auditory nerve of the chinchilla. The syllables [see text] produced by male speakers were used to synthesize noise vocoded speech stimuli containing one, two, three and four bands of envelope modulated noise. The ensemble response of the auditory nerve, computed by pooling the PST histograms across many auditory nerve fibers, revealed temporal patterns in the responses to the natural tokens that uniquely identified the stop consonants. The responses to the 3- and 4-band noise vocoded tokens contained temporal patterns that were nearly identical to those observed for the natural tokens, while the responses to the 1- and 2-band tokens were significantly different (p<0.0001). The ALSR, ALIR and autocorrelation of the pooled PST histograms represented the detail of the frequency spectrum for a naturally produced vowel, while the driven rate was unreliable. Each of these spectral analyses failed to reveal significant information about the noise vocoded vowels. These results suggest that temporal patterns in the responses of the auditory nerve can provide the cues necessary for the recognition of noise vocoded stop consonants.