Spatial selectivity to intracochlear electrical stimulation in the inferior colliculus is degraded after long-term deafness in cats

In an animal model of electrical hearing in prelingually deaf adults, this study examined the effects of deafness duration on response thresholds and spatial selectivity (i.e., cochleotopic organization, spatial tuning and dynamic range) in the central auditory system to intracochlear electrical stimulation. Electrically evoked auditory brain stem response (EABR) thresholds and neural response thresholds in the external (ICX) and central (ICC) nuclei of the inferior colliculus were estimated in cats after varying durations of neonatally induced deafness: in animals deafened <1.5 yr (short-deafened unstimulated, SDU cats) with a mean spiral ganglion cell (SGC) density of approximately 45% of normal and in animals deafened >2.5 yr (long-deafened, LD cats) with severe cochlear pathology (mean SGC density <7% of normal). LD animals were subdivided into unstimulated cats and those that received chronic intracochlear electrical stimulation via a feline cochlear implant. Acutely deafened, implanted adult cats served as controls. Independent of their stimulation history, LD animals had significantly higher EABR and ICC thresholds than SDU and control animals. Moreover, the spread of electrical excitation was significantly broader and the dynamic range significantly reduced in LD animals. Despite the prolonged durations of deafness the fundamental cochleotopic organization was maintained in both the ICX and the ICC of LD animals. There was no difference between SDU and control cats in any of the response properties tested. These findings suggest that long-term auditory deprivation results in a significant and possibly irreversible degradation of response thresholds and spatial selectivity to intracochlear electrical stimulation in the auditory midbrain.     

Responses of inferior colliculus neurons to double harmonic tones

The auditory system can segregate sounds that overlap in time and frequency, if the sounds differ in acoustic properties such as fundamental frequency (f0). However, the neural mechanisms that underlie this ability are poorly understood. Responses of neurons in the inferior colliculus (IC) of the anesthetized chinchilla were measured. The stimuli were harmonic tones, presented alone (single harmonic tones) and in the presence of a second harmonic tone with a different f0 (double harmonic tones). Responses to single harmonic tones exhibited no stimulus-related temporal pattern, or in some cases, a simple envelope modulated at f0. Responses to double harmonic tones exhibited complex slowly modulated discharge patterns. The discharge pattern varied with the difference in f0 and with characteristic frequency. The discharge pattern also varied with the relative levels of the two tones; complex temporal patterns were observed when levels were equal, but as the level difference increased, the discharge pattern reverted to that associated with single harmonic tones. The results indicated that IC neurons convey information about simultaneous sounds in their temporal discharge patterns and that the patterns are produced by interactions between adjacent components in the spectrum. The representation is "low-resolution," in that it does not convey information about single resolved components from either individual sound.     

Responses of neurons in inferior colliculus to variations in sound-source azimuth

This study aimed to classify the responses of single units in the auditory midbrain to acoustic stimuli presented in the free field in order to characterize those units likely to have a role in sound localization in the horizontal plane. The responses of 131 single units in the inferior colliculus of the cat and the brush-tailed possum were studied using tone and noise-burst stimuli presented from a speaker capable of movement at any point along a plane 10 degrees above the horizontal plane. Speaker positions along this plane are referred to as speaker azimuths; those on the same side as the recorded inferior colliculus as ipsilateral, and on the opposite side as contralateral, azimuths. For each unit, spike counts were measured as a function of azimuth either at the best frequency (BF) or using noise bursts. These functions are referred to as azimuth functions and were usually measured for at least two intensities, between 10 and 70 dB above threshold. The recording sites of most units were identified histologically with the aid of microlesions and were related to the major subdivisions of the inferior colliculus: the central nucleus (ICC), the lateral part of the external nucleus (ICX), and the rostroventral process (R-ICX). Two units were located in the pericentral nucleus and two in the dorsal nucleus of the lateral lemniscus. Two major classes of neuron were identified: omnidirectional and directionally sensitive. Omnidirectional units exhibited azimuth functions that were either flat or that declined gradually at progressively ipsilateral azimuths. For the latter units, discharge rates at all points monotonically increased with stimulus intensity. There was no indication, for either type of omnidirectional unit, of significant binaural interaction. A good correlation was found between the summed proportions of excitatory-excitatory (EE) and monaural (EO) units observed in dichotic studies (46-55%) and the proportion of omnidirectional units in the present study (47%). A subgroup of directionally sensitive units (36% of the total) displayed azimuth functions for which the azimuthal position of the discharge border or peak firing azimuth remained essentially unaltered over a range of stimulus intensities. These azimuth-selective units are likely to have a role in the detection of the location of stimuli in the horizontal plane and appear to include units that would be considered excitatory-inhibitory (EI) or delay sensitive in dichotic studies. The azimuths over which directionally sensitive units showed their marked directional effects were influenced by the position of the contralateral pinna.(ABSTRACT TRUNCATED AT 400 WORDS)     

Response of inferior colliculus neurons to electrical stimulation of the auditory nerve in neonatally deafened cats.

Response properties of neurons in the inferior colliculus (IC) were examined in control and profoundly deafened animals to electrical stimulation of the auditory nerve. Seven adult cats were used: two controls; four neonatally deafened (2 bilaterally, 2 unilaterally); and one long-term bilaterally deaf cat. All control cochleae were deafened immediately before recording to avoid electrophonic activation of hair cells. Histological analysis of neonatally deafened cochleae showed no evidence of hair cells and a moderate to severe spiral ganglion cell loss, whereas the long-term deaf animal had only 1-2% ganglion cell survival. Under barbiturate anesthesia, scala tympani electrodes were implanted bilaterally and the auditory nerve electrically stimulated using 100 micros/phase biphasic current pulses. Single-unit (n = 419) recordings were made through the lateral (LN) and central (ICC) nuclei of the IC; responses could be elicited readily in all animals. Approximately 80% of cells responded to contralateral stimulation, whereas nearly 75% showed an excitatory response to ipsilateral stimulation. Most units showed a monotonic increase in spike probability and reduction in latency and jitter with increasing current. Nonmonotonic activity was seen in 15% of units regardless of hearing status. Neurons in the LN exhibited longer latencies (10-25 ms) compared with those in the ICC (5-8 ms). There was a deafness-induced increase in latency, jitter, and dynamic range; the extent of these changes was related to duration of deafness. The ICC maintained a rudimentary cochleotopic organization in all neonatally deafened animals, suggesting that this organization is laid down during development in the absence of normal afferent input. Temporal resolution of IC neurons was reduced significantly in neonatal bilaterally deafened animals compared with acutely deafened controls, whereas neonatal unilaterally deafened animals showed no reduction. It would appear that monaural afferent input is sufficient to maintain normal levels of temporal resolution in auditory midbrain neurons. These experiments have shown that many of the basic response properties are similar across animals with a wide range of auditory experience. However, important differences were identified, including increased response latencies and temporal jitter, and reduced levels of temporal resolution.     

Glutamatergic and GABAergic regulation of neural responses in inferior colliculus to amplitude-modulated sounds

Recordings were made from single neurons in the rat inferior colliculus in response to sinusoidally amplitude-modulated sounds (10-s duration) presented to the contralateral ear. Neural responses were determined for different rates of modulation (0.5 Hz to 1 kHz) at a depth of 100%, and modulation transfer functions were generated based on firing rate (MTFFR) and vector strength (MTFVS). The effects of AMPA, NMDA, and GABAA receptor antagonists were examined by releasing drugs iontophoretically through a multibarrel pipette attached to a single-barrel recording pipette. Both the AMPA receptor antagonist, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX), and the NMDA receptor antagonist, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) resulted in a decrease in firing rate, and the GABAA receptor antagonist, bicuculline, produced an increase in the firing rate in most of the cells examined. In some cases, the shape of the MTFFR was modified slightly by receptor antagonists, but in most cases, the peak firing rate that determined a neuron's best modulation frequency remained the same. Also there were no changes during delivery of either excitatory or inhibitory antagonists in the maximum response synchrony at the peak of the MTFVS although some changes were noticed at off-peak modulation rates particularly with the AMPA receptor antagonist, NBQX.     

Auditory temporal processing: responses to sinusoidally amplitude-modulated tones in the inferior colliculus

Time-varying envelopes are a common feature of acoustic communication signals like human speech and induce a variety of percepts in human listeners. We studied the responses of 109 single neurons in the inferior colliculus (IC) of the anesthetized Mongolian gerbil to contralaterally presented sinusoidally amplitude-modulated (SAM) tones with a wide range of parameters. Modulation transfer functions (MTFs) based on average spike rate (rMTFs) showed regions of enhancement and suppression, where spike rates increased or decreased respectively as stimulus modulation depth increased. Specifically, almost all IC rMTFs could be described by some combination of a primary and a secondary region of enhancement and an intervening region of suppression, with these regions present to varying degrees in individual rMTFs. rMTF characteristics of most neurons were dependent on sound pressure level (SPL). rMTFs in most neurons with "onset" or "onset-sustained" peri-stimulus time histograms (PSTHs) in response to brief pure tones showed only a peaked primary region of enhancement. The region of suppression tended to occur in neurons with "sustained" or "pauser" PSTHs, and usually emerged at higher SPLs. The secondary region of enhancement was only found in eight neurons. The lowest modulation frequency at which the spike rate reached a clear peak ("best modulation frequency" or BMF) was measured. All but two mean BMFs lay between 0 and 100 Hz. Fifty percent of the 49 neurons tested over at least a 20-dB range of SPLs showed a BMF variation larger than 66% of their mean BMF. MTFs based on vector strength (tMTFs) showed a variety of patterns; although mostly similar to those reported from the cochlear nucleus, tMTFs of IC neurons showed higher maximum values, smaller dynamic range with depth, and a lower high-frequency limit for significant phase locking. Systematic and large increases in phase-lead commonly occurred as SPL increased. rMTFs measured at multiple carrier frequencies (F(c)s) showed that the suppressive region was not the result of sideband inhibition. There was no systematic relationship between BMF and F(c) of stimulation in the cells studied, even at low carrier frequencies. The results suggest various possible mechanisms that could create IC MTFs, and strongly support the idea that inhibitory inputs shape the rMTF by sharpening regions of enhancement and creating a suppressive region. The paucity of BMFs above 100 Hz argues against simple rate-coding schemes for pitch. Finally, any labeled line or topographic representation of modulation frequency is unlikely to be independent of SPL.     

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

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, and 2) discrimination of successive SAM pulse trains is based on temporal resolution of the envelope frequencies. Overall, our animal model provides a robust framework for future studies of behavioral discrimination and central neural temporal processing of electrical signals applied to the deaf cochlea by a cochlear implant.     

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

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

Comparison of responses of neurons in the mouse inferior colliculus to current injections, tones of different durations, and sinusoidal amplitude-modulated tones

We made in vivo whole cell patch-clamp recordings from the inferior colliculus of young-adult, anesthetized C57/Bl6 mice to compare the responses to constant-current injections with the responses to tones of different duration or to sinusoidal amplitude-modulated (SAM) tones. We observed that voltage-dependent ion channels contributed in several ways to the response to tones. A sustained response to long tones was observed only in cells showing little accommodation during current injection. Cells showing burst-onset firing during current injection showed a small response to SAM tones, whereas burst-sustained cells showed a good response to SAM tones. The hyperpolarization-activated nonselective cation channel I(h) had a special role in shaping the responses: I(h) was associated with an increased excitability, with chopper and pauser responses, and with an afterhyperpolarization following tones. Synaptic properties were more important in determining the responses to tones of different durations. A short-latency inhibitory response appeared to contribute to the long-pass response in some cells and short-pass and band-pass neurons were characterized by their slow recovery from synaptic adaptation. Cells that recovered slowly from synaptic adaptation showed a relatively small response to SAM tones. Our results show an important role for both intrinsic membrane properties -- most notably the presence of I(h) and the extent of accommodation -- and synaptic adaptation in shaping the response to tones in the inferior colliculus.     

The responses of neurons in subdivisions of the inferior colliculus of cats to tonal,noise and vocal stimuli

The aim of this study was to gain information from anesthetized cats about the differential coding properties of neurons in the three major subdivisions of the inferior colliculus: the central (CNIC) and external (EN) nuclei and dorsal cortex (DC). Stimuli were presented in the free field from a speaker facing the contralateral pinna. For each unit, the characteristic frequency (CF, where threshold was lowest) was determined, and impulse rates to CF tone bursts, noise bursts and four feline vocal stimuli were measured as a function of increasing sound pressure level (rate/level functions). Peristimulus-time histograms were computed for responses to all stimuli. Sustained firing patterns to CF stimuli were observed for 81% of units in CNIC, for 50% of units in EN and 27% of units in DC. Sustained discharges were evoked by noise in 78–100% of units in all regions, and by at least one vocal stimulus in 86% of units in CNIC, 82% in EN and 55% in DC. In the CNIC, non-monotonic rate/level functions to CF stimuli were more common (41%) than either monotonie or plateau functions, whereas the reverse was the case with noise and vocal stimuli. Non-monotonic functions were uncommon to any stimulus in EN and DC (21–24%). Vocal stimuli were more effective in terms of higher firing rates than noise or CF stimuli in 27% of units in CNIC, 82% in EN and 72% in DC. There were no units that responded exclusively to one vocal stimulus, but a high proportion of units in EN responded strongly to broad band stimuli, and some of these showed clear preferences for one vocal stimulus over others.     

Disynaptic inhibition of omnipause neurons following electrical stimulation of the superior colliculus in alert cats

We investigated the synaptic organization responsible for the inhibition of omnipause neurons (OPNs) following stimulation of the superior colliculus (SC) in alert cats. Stimulation electrodes were implanted bilaterally in the rostral and caudal SC where a short-pulse train induced small and large saccades, respectively. Effects of single-pulse stimulation on OPNs were examined with intracellular and extracellular recordings. In contrast to monosynaptic excitatory postsynaptic potentials, which were induced by rostral SC stimulation, inhibitory postsynaptic potentials were induced with disynaptic latencies (1.3--1.9 ms) from both the rostral and caudal SC in most OPNs. Analysis of a larger extracellular sample complemented intracellular observations. Monosynaptic activation of OPNs was elicited more frequently from rostral sites than from caudal sites, whereas spike suppression with disynaptic latencies was induced by caudal as well as rostral stimulation with similar frequencies. The results imply that disynaptic inhibition is produced by activation of SC cells that are distributed over wide regions related to saccades of different sizes. We suggest that signals from these neurons initiate a saccadic pause of OPNs through single inhibitory interneurons.     

Temporal properties of chronic cochlear electrical stimulation determine temporal resolution of neurons in cat inferior colliculus

As cochlear implants have become increasingly successful in the rehabilitation of adults with profound hearing impairment, the number of pediatric implant subjects has increased. We have developed an animal model of congenital deafness and investigated the effect of electrical stimulus frequency on the temporal resolution of central neurons in the developing auditory system of deaf cats. Maximum following frequencies (Fmax) and response latencies of isolated single neurons to intracochlear electrical pulse trains (charge balanced, constant current biphasic pulses) were recorded in the contralateral inferior colliculus (IC) of two groups of neonatally deafened, barbiturate-anesthetized cats: animals chronically stimulated with low-frequency signals (< or = 80 Hz) and animals receiving chronic high-frequency stimulation (> or = 300 pps). The results were compared with data from unstimulated, acutely deafened and implanted adult cats with previously normal hearing (controls). Characteristic differences were seen between the temporal response properties of neurons in the external nucleus (ICX; approximately 16% of the recordings) and neurons in the central nucleus (ICC; approximately 81% of all recordings) of the IC: 1) in all three experimental groups, neurons in the ICX had significantly lower Fmax and longer response latencies than those in the ICC. 2) Chronic electrical stimulation in neonatally deafened cats altered the temporal resolution of neurons exclusively in the ICC but not in the ICX. The magnitude of this effect was dependent on the frequency of the chronic stimulation. Specifically, low-frequency signals (30 pps, 80 pps) maintained the temporal resolution of ICC neurons, whereas higher-frequency stimuli significantly improved temporal resolution of ICC neurons (i.e., higher Fmax and shorter response latencies) compared with neurons in control cats. Furthermore, Fmax and latencies to electrical stimuli were not correlated with the tonotopic gradient of the ICC, and changes in temporal resolution following chronic electrical stimulation occurred uniformly throughout the entire ICC. In all three experimental groups, increasing Fmax was correlated with shorter response latencies. The results indicate that the temporal features of the chronically applied electrical signals critically influence temporal processing of neurons in the cochleotopically organized ICC. We suggest that such plastic changes in temporal processing of central auditory neurons may contribute to the intersubject variability and gradual improvements in speech recognition performance observed in clinical studies of deaf children using cochlear implants.