Neil J. Ingham

GABAergic Inhibition Controls Neural Gain in Inferior Colliculus Neurons Sensitive to Interaural Time Differences

We investigated the role of GABAergic inhibition on the responses of inferior colliculus (IC) neurons sensitive to interaural time differences (ITDs) in anesthetized guinea pigs. Responses to static and dynamic ITDs were obtained before, during, and after recovery from ionotophoretic application of GABA, or antagonists to the GABAA receptor gabazine and bicuculline. For most neurons, a linear relationship was observed between discharge rates evoked by a particular ITD during drug application and control discharge rates. Blocking GABAergic inhibition, or adding exogenous GABA, scaled IC discharge rates in a multiplicative (divisive) and/or additive (subtractive) manner. When the influence of iontophoresed GABA antagonists or exogenous GABA on discharge rates was accounted for, GABAergic inhibition was found to have no effect on the ITD tuning properties of IC neurons. The tuning sharpness of ITD functions, the ITD that evoked 50% response magnitude, and the relative symmetry of ITD functions around their peak response were unaffected by blockade of inhibition or addition of tonic inhibition. However, the ability of neurons to discriminate between ITDs by virtue of differences in their discharge rate was altered by blocking or adding GABA. We propose that inhibition in the IC is involved in the control of the neural gain of the output of IC neurons rather than the regulation of ITD tuning. This gain control appears to arise from a combination of additive and multiplicative processes, and may involve mechanisms such as shunting inhibition or changes in the efficacy of inhibitory and excitatory inputs.

Contralateral inhibitory and excitatory frequency response maps in the mammalian cochlear nucleus

There is increasing evidence that the responses of single units in the mammalian cochlear nucleus can be altered by the presentation of contralateral stimuli, although the functional significance of this binaural responsiveness is unknown. To further our understanding of this phenomenon we recorded single‐unit (n = 110) response maps from the cochlear nucleus (ventral and dorsal divisions) of the anaesthetized guinea pig in response to presentation of ipsilateral and contralateral pure tones. Many neurones showed no evidence of input from the contralateral ear (n = 41) but other neurones from both ventral and dorsal cochlear nucleus showed clear evidence of contralateral inhibitory input (n = 61). Inhibitory response patterns were divided into two groups. In 36 neurones, contralateral tone‐evoked inhibition was closely aligned with the ipsilateral excitatory response map (± 0.33 octaves) often extending to low stimulus levels. In 25 neurones, higher threshold contralateral inhibitory responses were found, mostly centred at frequencies greater than 0.33 octaves below the ipsilateral excitation. A few neurones (n = 8) exhibited responses consistent with excitatory input from the contralateral ear, which was closely aligned with the ipsilateral excitation, and were found exclusively in the dorsal cochlear nucleus. The latency of the contralateral interaction was, on average, longer than the ipsilateral latency. Interaural level difference curves are similar to other reports from the cochlear nucleus. Our results are consistent with the idea that contralateral interactions arise from a variety of direct and indirect neuronal projections.

The time course of recovery from suppression and facilitation from single units in the mammalian cochlear nucleus.

The responses to two identical, consecutive pure tone stimuli with varying inter-stimulus intervals (delta ts) were measured for 89 neurons in the cochlear nucleus of the anaesthetised guinea pig. We observed two main effects; either a decrease (suppression) or an increase (facilitation) in response to the second tone followed by an exponential recovery. Response behaviour correlated with the unit type; primary-like, primary-like with notch and transient-chopper units showed a recovery from suppression that was very similar to that already reported in the auditory nerve. For chopper units the strength of the adaptation was correlated with the units regularity of spike discharge; sustained chopper (CS) units showed less suppression than transient choppers. Onset units showed complete suppression at short delta ts. Pause/Build (PB) units responded with increased activity to the second tone. In contrast to previous studies in the cochlear nucleus the recovery from suppression or facilitation was well described by a single exponential function, enabling us to define a recovery time constant and a maximum suppression/facilitation. There appeared to be a hierarchy in the time constant of recovery with PB and CS units showing the longest recovery times and onset units showing the shortest.

Hair cell loss in the aged guinea pig cochlea.

The various effects of ageing on the auditory system, collectively termed presbycusis, are being studied across a wide range of animal species, including humans. One contributing factor to presbycusis is thought to be losses of the sensory hair cells in the cochlea. In this study, hair cell counts were obtained from cochleas of pigmented guinea pigs (Cavia porcellus) at ages ranging from 11 days to 4 years 7 months, using scanning electron microscopy to visualize the organ of Corti. Representative samples of the basal, middle and apical turn of the cochlea were photographed for analysis. Hair cell loss was observed, even in young animals. However, the loss was greater in the aged animals, but was not distributed evenly throughout the length of the cochlea. No significant loss of hair cells was seen in the basal (high frequency) or middle turn of the cochlea of the aged animals. In the apical (low frequency) turn, there was a significant loss of hair cells in all rows of outer hair cells (up to around 20%), and was most severe in the third row. There was no loss of apical inner hair cells in the aged animals.

Enhancement of forward suppression begins in the ventral cochlear nucleus

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 (16.9–33.5 dB) and, in the VCN, these recovered with the fastest time constants (14.1–19.9 ms). Neurons with sustained discharge demonstrated reduced masking (8.9–12.1 dB) and recovery time constants of 27.2–55.6 ms. 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.

The Effect of Reverberation on the Temporal Representation of the F0 of Frequency Swept Harmonic Complexes in the Ventral Cochlear Nucleus

When listening in an enclosed space, part of the sound has travelled to the listener directly from its source. In addition the listener receives multiple delayed and attenuated copies of the sound as it is reflected from the room’s surfaces, an effect referred to as reverberation. This series of reflections has a filtering effect, introducing distortion in both the spectral and temporal domains. Spectral transitions are smeared in time and the introduction of slowly decaying “tails” effectively applies a low-pass filter to the temporal envelope. Since each reflection is added back to the original “direct” sound with random phase, envelope periodicity tends to be disrupted. Although reverberation is often exploited as a means of delivering the necessary sound level to audiences in auditoria it has long been acknowledged that the resulting distortion can have a deleterious effect on the intelligibility of complex time-varying stimuli such as speech (Knudsen 1929; Santon 1976; Nabĕlek et al. 1989). Human psychophysical studies (Culling et al. 1994) have demonstrated that the combination of relatively mild reverberation and fundamental (F0) frequency modulation at rates commonly found in speech disrupts listeners’ ability to exploit differences in F0 to perceptually segregate two competing sound sources. Despite the obvious importance of reverberation in the intelligibility of speech, to our knowledge this has yet to be explored from a physiological perspective. As a first attempt at understanding the effects of reverberation on the representation of complex sounds in the mammalian auditory system we have recorded the responses of single units in the ventral cochlear nucleus to the F0 of frequency swept harmonic complexes with and without reverberation. Here we show that in many single units in the ventral cochlear nucleus (VCN) reverberation degrades the temporal representation of F0. Only units responding to resolved harmonics are able to maintain a representation of the F0 through all reverberation conditions. These results are consistent with the hypothesis that reverberation disrupts the phase