Area-dependent change of response in the rat's inferior colliculus to intracochlear electrical stimulation following neonatal cochlear damage.

To understand brain changes caused by auditory sensory deprivation, we recorded local-field potentials in the inferior colliculus of young adult rats with neonatal cochlear damage produced by systemic injections of amikacin. The responses were elicited by electrical stimulation of the entire cochlea and recorded at various locations along a dorsolateral-ventromedial axis of the inferior colliculus. We found that hair cells were completely destroyed and spiral ganglion neurons were severely damaged in the basal cochleae of amikacin-treated animals. Hair cells as well as spiral ganglion neurons were damaged also in the middle and apical areas of the cochlea, with the damage being greater in the middle than the apical area. Amplitudes of local-field potentials were reduced in the ventromedial inferior colliculus, but enhanced in the dorsolateral inferior colliculus. Latencies of responses were increased over the entire structure. The enhancement of responses in the dorsolateral inferior colliculus was in contrast with the damage of hair cells and spiral ganglion cells in the apical part of the cochlea. This contrast along with the overall increase of latencies suggests that early cochlear damage can alter neural mechanisms within the inferior colliculus and/or the inputs to this midbrain structure.

Behavioral consequences of unilateral inferior colliculus lesions in the rat.

This study was carried out to determine the behavioral sensitivity to sound of rats with unilateral lesions of inferior colliculus (IC) located ipsilateral or contralateral to the projection pathway from one ear. Absolute thresholds for the detection of a broad-band noise burst were compared for rats with a profound conductive hearing loss in one ear and a lesion placed either ipsilateral or contralateral to the normally functioning ear. The rats were trained to make withdrawal responses to avoid a shock when they detected the presence of a noise burst. Sound pressure level was systematically lowered to obtain psychophysical curves from which absolute thresholds could be determined. Complete lesions of the contralateral IC resulted in substantial elevations in absolute threshold relative to normal whereas equivalent lesions of the ipsilateral IC produced relatively little elevation. In neither case did unilateral destruction of the IC produce a total inability to respond to sound. Contralateral IC lesions that included the dorsal nucleus of the lateral lemniscus (DNLL) produced a significantly greater elevation in behavioral thresholds than complete lesions limited to the IC. The results indicate a predominance of the contralateral over the ipsilateral pathway to IC for maintaining normal thresholds. They also indicate that other pathways that bypass the IC are likely involved in detecting the presence of a sound.

Diminished behavioral and neural sensitivity to sound modulation is associated with moderate developmental hearing loss.

The acoustic rearing environment can alter central auditory coding properties, yet altered neural coding is seldom linked with specific deficits to adult perceptual skills. To test whether developmental hearing loss resulted in comparable changes to perception and sensory coding, we examined behavioral and neural detection thresholds for sinusoidally amplitude modulated (sAM) stimuli. Behavioral sAM detection thresholds for slow (5 Hz) modulations were significantly worse for animals reared with bilateral conductive hearing loss (CHL), as compared to controls. This difference could not be attributed to hearing thresholds, proficiency at the task, or proxies for attention. Detection thresholds across the groups did not differ for fast (100 Hz) modulations, a result paralleling that seen in humans. Neural responses to sAM stimuli were recorded in single auditory cortex neurons from separate groups of awake animals. Neurometric analyses indicated equivalent thresholds for the most sensitive neurons, but a significantly poorer detection threshold for slow modulations across the population of CHL neurons as compared to controls. The magnitude of the neural deficit matched that of the behavioral differences, suggesting that a reduction of sensory information can account for limitations to perceptual skills.

Changes in projections to the inferior colliculus following early hearing loss in rats.

The purpose of this study was to investigate the effects of early hearing loss on the anatomy of the central auditory system, specifically, the ascending projections to the inferior colliculus (IC). We compared normal animals with animals deafened during early development by administration of amikacin, an ototoxic antibiotic that is known to destroy the hair cells in the inner ear. The amikacin was injected subcutaneously every day from postnatal days P7 to P16. A retrograde tract tracer, Fluoro-Gold (FG), was then injected unilaterally directly into the IC at either 4 weeks of age or 12 weeks of age. After axonal transport the animals were sacrificed and their brains were prepared for histology. The FG labeled neurons in the cochlear nucleus (CN) and the dorsal nucleus of lateral lemniscus (DNLL) were counted for each of the animals in the two age groups. For deaf animals sacrificed at 4 weeks of age there was a significant reduction in the number of FG labeled neurons that was limited to the ventral CN ipsilateral to the tracer injection. For deaf animals sacrificed at 12 weeks of age, however, there was a significant decrease in the number of labeled cells in both dorsal and ventral CN on both sides of the brain. In DNLL there was no change in the number or pattern of labeled neurons. The results show that neonatal deafness reduces the number of labeled neurons projecting from the CN to the IC with the effect being more evident during later stages of deafness. In contrast, there are no significant changes in the projections from DNLL to IC.

Time dependence of binaural responses in the rat's central nucleus of the inferior colliculus.

Recordings were made from single neurons in the rat's central nucleus of the inferior colliculus. Excitatory/inhibitory binaural interactions and interaural-level difference curves were determined for responses to 100 ms dichotic tone bursts presented to the left and right ears simultaneously. Most neurons with sustained responses to tone bursts had the same binaural response type throughout the 100 ms stimulus period. However, some neurons (39% of our sample) showed qualitatively different binaural response types during the early and late parts of the stimulus (the first 20 ms versus the last 80 ms of the tone burst). Also, for many neurons with consistent early and late binaural response patterns, the strength of binaural interaction was different during the early and late periods. For example, for neurons excited by the contralateral ear and inhibited by the ipsilateral ear during the entire 100 ms period (the most common binaural response type), the degree of inhibition was generally greater during the later part of a stimulus. This change in the strength and/or quality of binaural interaction during dichotic stimulation likely reflects a complex pattern of converging excitatory and inhibitory inputs to the inferior colliculus from lower brainstem structures as well as the time course of local synaptic events. The temporal properties of binaural interaction may influence how sound source location is represented in the central auditory system.

Time-dependent effects of ipsilateral stimulation on contralaterally elicited responses in the rat's central nucleus of the inferior colliculus.

Recordings were made from single neurons in the rat's central nucleus of the inferior colliculus (ICc). Binaural responses were studied when dichotic tone bursts with various interaural-level differences were presented simultaneously or with a contralateral delay. These dichotic tone bursts allowed us to probe temporal changes in the effect produced by an ipsilateral sound on a contralaterally elicited response. Most of the neurons in the rat's ICc were excited by contralateral and inhibited by ipsilateral stimulation. For the majority of neurons with excitatory/inhibitory interactions, the early part of an ipsilateral stimulus caused stronger inhibition than the late part. The ipsilateral stimulus frequently produced an excitatory or inhibitory "offset" effect that was apparent soon after cessation of the stimulus. For many neurons, this aftereffect substantially changed the strength and temporal firing pattern of the response elicited by a lagging contralateral stimulus. Our results suggest that there are time-dependent changes in the effect of ipsilateral stimulation on the pattern and strength of responses to contralateral stimulation. These effects frequently outlast the duration of a leading ipsilateral stimulus. These characteristics of binaural interaction likely reflect the time courses of converging excitatory and inhibitory synaptic inputs to ICc neurons as well as the intrinsic membrane properties of those neurons.

Uniform degradation of auditory acuity in subjects with normal hearing leads to unequal precedence effects.

OBJECTIVE: The aim of this study was to investigate whether a controlled unilateral reduction in auditory acuity at the higher audiometric frequencies would have an effect on the variability in responses obtained on a task designed to measure the precedence effect. DESIGN: The experiment was conducted with participants located in a large sound proof, anechoic room, and psychophysical tests were conducted with long-duration noise burst stimuli. Reduction in auditory acuity was created by inserting a specially designed earplug in the ear of participants with normal hearing. The earplugs produced a highly reliable increase in the thresholds for detecting high-frequency sounds in the blocked ear with the largest effect at the highest frequencies (4 and 8 kHz). Across-participant variability in tone-detection threshold was less than +/-5 dB. The measurement of lag-burst thresholds with and without the insertion of earplugs was used to characterize the precedence effect. The lag-burst threshold was defined as the shortest lag-burst delay that yielded a perception of two different noise bursts. RESULTS: Although performance was stable across participants in the condition without the earplug, a substantial increase in variability in the lag-burst thresholds was found in the earplug condition. CONCLUSIONS: These results indicate that a uniform unilateral degradation in auditory acuity leads to increased variability in performance on tasks measuring fusion in the precedence effect. The outcome suggests that variable perception of the precedence effect by individuals with clinically diagnosed hearing loss might be due to factors other than a reduction in auditory acuity per se.

Anatomical projections of the nuclei of the lateral lemniscus in the albino rat (Rattus norvegicus).

The ascending projections to the lateral lemniscal nuclei and the inferior colliculus were investigated in the albino rat by using Fluoro-Gold, either alone or in combination with other retrograde tract tracers. Injections were made into the central nucleus of the inferior colliculus (ICC), the dorsal nucleus of the lateral lemniscus (DNLL), the intermediate nucleus of the lateral lemniscus (INLL), or the ventral nucleus of the lateral lemniscus (VNLL). The ICC receives both ipsilateral and contralateral projections from the DNLL and the lateral superior olive, major ipsilateral projections from the INLL, VNLL, medial superior olive, and superior paraolivary nucleus, and major contralateral projections from both dorsal and ventral cochlear nucleus. The DNLL receives a similar pattern of projections from the auditory lower brainstem nuclei. The INLL, in contrast, receives its major projections from the ipsilateral VNLL, lateral superior olive, medial superior olive, superior paraolivary nucleus, and medial nucleus of the trapezoid body, but does not receive a heavy projection from the contralateral lateral superior olive. It receives a major contralateral projection from the ventral cochlear nucleus, but a much lighter projection from the contralateral dorsal cochlear nucleus. The VNLL receives projections from the ipsilateral medial nucleus of the trapezoid body and the contralateral ventral cochlear nucleus, but does not receive projections from the medial or lateral superior olives, the superior paraolivary nucleus, or the dorsal cochlear nucleus. Thus, the three primary subdivisions of the rat's lateral lemniscus can be distinguished from each other on the basis of their distinctive projection patterns.

Anatomical plasticity in brainstem auditory nuclei following unilateral ablation of the inferior colliculus in neonatal rats.

Anatomical plasticity of projections from brainstem auditory structures to the inferior colliculus (IC) was examined in albino rats to determine the effects of unilateral destruction of the IC during early development. The IC in the right hemisphere was destroyed by aspiration on postnatal day 3. Upon reaching adulthood, the rats were examined by retrograde tract tracing methods with fluoro-gold (FG) and [3H]-glycine to determine patterns of brainstem projections to the undamaged left IC. In our FG experiments, the results confirmed the presence of aberrant crossed projections from the right medial superior olive (MSO) to the undamaged left IC. Following injections of [3H]-glycine or FG into the undamaged left IC, however, no other aberrant projections were found in the superior olive, including those from the ipsilateral lateral superior olive (LSO) or the superior paraolivary nucleus (SPN). These results suggest that projections from the MSO to the IC may have the latent ability to create aberrant crossed projections during development. On the other hand, the neurons in LSO and SPN do not form aberrant projections following early unilateral IC lesions.

Detection of sinusoidal amplitude modulated sounds: deficits after bilateral lesions of auditory cortex in the rat.

The ability of rats to detect the presence of sinusoidal amplitude modulation (AM) of a broadband noise carrier was determined before and after bilateral ablation of auditory cortex. The rats were trained to withdraw from a drinking spout to avoid a shock when they detected a modulation of the sound. Sensitivity was evaluated by testing the rats at progressively smaller depths of modulation. Psychophysical curves were produced to describe the limits of detection at modulation rates of 10, 100 and 1000Hz. Performance scores were based on the probability of withdrawal from the spout during AM (warning periods) relative to withdrawal during the un-modulated noise (safe periods). A threshold was defined as the depth of modulation that produced a score halfway between perfect avoidance and no avoidance (performance score=0.5). Bilateral auditory cortical lesions resulted in significant elevations in threshold for detection of AM at rates of 100 and 1000Hz. No significant shift was found at a modulation rate of 10Hz. The magnitude of the deficit for AM rates of 100 and 1000Hz was positively correlated with the size of the cortical lesion. Substantial deficits were found only in animals with lesions that included secondary as well as primary auditory cortical areas. The results show that the rat's auditory cortex is important for processing sinusoidal AM and that its contribution is most apparent at high modulation rates. The data suggest that the auditory cortex is a crucial structure for maintaining normal sensitivity to temporal modulation of an auditory stimulus.

Responses of neurons in the rat's ventral nucleus of the lateral lemniscus to amplitude-modulated tones.

Recordings were made from single neurons in the rat's ventral nucleus of the lateral lemniscus (VNLL) to determine responses to amplitude-modulated (AM) tones. The neurons were first characterized on the basis of their response to tone bursts presented to the contralateral ear and a distinction was made between those with transient onset responses and those with sustained responses. Sinusoidal AM tones were then presented to the contralateral ear with a carrier that matched the neuron's characteristic frequency (CF). Modulation transfer functions were generated on the basis of firing rate (MTF(FR)) and vector strength (MTF(VS)). Ninety-two percent of onset neurons that responded continuously to AM tones had band-pass MTF(FR)s with best modulation frequencies from 10 to 300 Hz. Fifty-four percent of sustained neurons had band-pass MTF(FR)s with best modulation frequencies from 10 to 500 Hz; other neurons had band-suppressed, all-pass, low-pass, or high-pass functions. Most neurons showed either band-pass or low-pass MTF(VS). Responses were well synchronized to the modulation cycle with maximum vector strengths ranging from 0.37 to 0.98 for sustained neurons and 0.78 to 0.99 for onset neurons. The upper frequency limit for response synchrony was higher than that reported for inferior colliculus, but lower than that seen in more peripheral structures. Results suggest that VNLL neurons, especially those with onset responses to tone bursts, are sensitive to temporal features of sounds and narrowly tuned to different modulation rates. However, there was no evidence of a topographic relation between dorsoventral position along the length of VNLL and best modulation frequency as determined by either firing rate or vector strength.

Behavioral limits of auditory temporal resolution in the rat: amplitude modulation and duration discrimination.

Thresholds for detecting the presence of amplitude modulation in a noise carrier were determined for rats using conditioned avoidance procedures. There was a progressive increase in threshold with modulation rates between 5 Hz and 2 kHz. Further tests were conducted to determine difference thresholds for detecting an increase in modulation rate for standard rates of 10, 50, and 100 Hz. The size of the difference threshold increased progressively as the standard rate increased. In addition, thresholds for detecting an increase in the duration of a noise burst were determined for various standard durations. The difference thresholds were constant for values between 10 and 50 ms but increased progressively, with standard durations between 0.1 and 1.0 s.

GABAB receptor-mediated presynaptic inhibition of glutamatergic transmission in the inferior colliculus.

Whole-cell patch clamp recordings were made from ICC neurons in brain slices of 9-16 day old rats. Postsynaptic currents were evoked by electrical stimulation of the lemniscal inputs. Excitatory postsynaptic currents (EPSCs) were isolated pharmacologically by blocking GABA(A) and glycine receptors. EPSCs were further dissected into AMPA and NMDA receptor-mediated responses by adding the receptor antagonists, APV and CNQX, respectively. The internal solution in the recording electrodes contained CsF and TEA to block K(+) channels that might be activated by postsynaptic GABA(B) receptors. The modulatory effects of GABA(B) receptors on EPSCs in ICC neurons were examined by bath application of the GABA(B) receptor agonist, baclofen, and the antagonist, CGP 35348. The amplitudes of EPSCs in ICC neurons were reduced to 34.4+/-3.2% of the control by baclofen (5-10 microM). The suppressive effect by baclofen was concentration-dependent. The reduction of the EPSC amplitude was reversed by CGP35348. The ratio of the 2nd to 1st EPSCs evoked by paired-pulse stimulation was significantly increased after application of baclofen. These results suggest that glutamatergic excitation in the ICC can be modulated by presynaptic GABA(B) receptors. In addition, baclofen reduced NMDA EPSCs more than AMPA EPSCs. The GABA(B) receptor-mediated modulation of glutamatergic excitation in the ICC provides a likely mechanism for preventing overstimulation and/or regulating the balance of excitation and inhibition involved in processing auditory information.

Responses of neurons in the rat's ventral nucleus of the lateral lemniscus to monaural and binaural tone bursts.

Responses to monaural and binaural tone bursts were recorded from neurons in the rat's ventral nucleus of the lateral lemniscus (VNLL). Most of the neurons (55%) had V- or U-shaped frequency-tuning curves with a single clearly defined characteristic frequency (CF). However, many neurons had more complex, multipeaked tuning curves (37%), or other patterns (8%). Temporal firing patterns included both onset and sustained responses to contralateral tone bursts. Onset and sustained responses were distributed along the dorsoventral length of VNLL with no indication of segregation into different regions. Onset neurons had shorter average first-spike latencies than neurons with sustained responses (means, 8.3 vs. 14.8 ms). They also had less jitter, as reflected in the SD of first-spike latencies, than neurons with sustained responses (means, 0.59 and 4.2 ms, respectively). The extent of jitter decreased with an increase in stimulus intensity for neurons with sustained responses, but remained unchanged for onset neurons tested over the same range. Many neurons had binaural responses, primarily of the excitatory/inhibitory (EI) type, widely distributed along the dorsoventral extent of VNLL. Local application of the AMPA receptor antagonist NBQX reduced excitatory responses, indicating that responses were dependent on synaptic activity and not recorded from passing fibers. The results show that many neurons in VNLL have a precision of timing that is well suited for processing auditory temporal information. In the rat, these neurons are intermingled among cells with less precise temporal response features and include cells with binaural as well as monaural responses.

Contribution of AMPA, NMDA, and GABA(A) receptors to temporal pattern of postsynaptic responses in the inferior colliculus of the rat.

The central nucleus of the inferior colliculus (ICC) is a major site of synaptic interaction in the central auditory system. To understand how ICC neurons integrate excitatory and inhibitory inputs for processing temporal information, we examined postsynaptic responses of ICC neurons to repetitive stimulation of the lateral lemniscus at 10-100 Hz in rat brain slices. The excitatory synaptic currents mediated by AMPA and NMDA receptors and the inhibitory current mediated by GABA(A) receptors were pharmacologically isolated and recorded by whole-cell patch-clamp techniques. The response kinetics of AMPA receptor-mediated EPSCs and GABA(A) receptor-mediated IPSCs were similar and much faster than those of NMDA receptor-mediated EPSCs. AMPA EPSCs could follow each pulse of stimulation at a rate of 10-100 Hz but showed response depression during the course of repetitive stimulation. GABA(A) IPSCs could also follow stimulus pulses over this frequency range but showed depression at low rates and facilitation at higher rates. NMDA EPSCs showed facilitation and temporal summation in response to repetitive stimulation, which was most pronounced at higher rates of stimulation. GABA(A) inhibition suppressed activation of NMDA receptors and reduced both the degree of AMPA EPSC depression and the extent of temporal summation of NMDA EPSCs. The results indicate that GABA(A) receptor-mediated inhibition plays a crucial role in maintaining the balance of excitation and inhibition and in allowing ICC neurons to process temporal information more precisely.

Regulation of auditory responses in the central nucleus of the inferior colliculus by tetraethylammonium-sensitive potassium channels.

The role of potassium channels in regulating spontaneous firing and sound-evoked responses in the central nucleus of the inferior colliculus was studied by recording single-unit activity before and during iontophoretic application of a nonspecific potassium channel blocker, tetraethylammonium (TEA). Tone bursts and sinusoidal amplitude-modulated tones were used to evoke auditory responses. Our results show that release of TEA increased the width of spikes for all neurons tested. There was an increase in spontaneous firing for most of the neurons. There was also an increase in responses to tone bursts for most of the neurons, although in some cases there was a reduction in the evoked responses. TEA also increased the firing rate in responses to sinusoidal amplitude-modulated sounds in the majority of the neurons tested. For some neurons, the change in firing reduced the selectivity of responses for particular rates of modulation. There was also a reduction in the synchrony of action potentials to the modulation envelope in many cells. Our results show that potassium channels are important for regulating the strength of sound-evoked responses and the level of spontaneous activity, and determining the temporal properties of responses to amplitude-modulated sounds.

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.

AMPA and NMDA receptors mediate synaptic excitation in the rat's inferior colliculus.

The synaptic mechanisms underlying excitation in the rat's central nucleus of the inferior colliculus (ICC) were examined by making whole-cell patch clamp recordings in brain slice preparations of the auditory midbrain. Responses were elicited by current pulse stimulation of the lateral lemniscus and recordings were made in ICC using either current clamp or voltage clamp methods. The excitatory postsynaptic responses in either current or voltage clamp mode consisted of two distinct components, an early component that could be blocked by bath application of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), and a later component that could be blocked by application of the N-methyl-D-aspartate (NMDA) receptor antagonists, (+/-)-2-amino-5-phosphonovaleric acid (APV) or (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). Both AMPA and NMDA receptor-mediated responses were present at resting potential and could be isolated pharmacologically by application of receptor antagonists. Voltage clamp experiments revealed that the NMDA receptor-mediated current was voltage-dependent and increased in magnitude as the cell membrane was depolarized. This NMDA receptor-mediated response was enhanced at resting potential when Mg(2+) was eliminated from the bath solution. The ratio of response amplitudes associated with the late and early components, an estimate of the relative contribution of NMDA and AMPA receptor types, changed with age. There was a progressive decline in the ratio between 9 and 13 days of age, but no further reduction between days 13 and 16. The data show that both AMPA and NMDA receptors are important for determining excitatory responses in the ICC and that both receptor types probably play a role in auditory processing after the onset of hearing.

Contribution of AMPA and NMDA receptors to excitatory responses in the inferior colliculus.

Brain slice studies of neurons in the central nucleus of the inferior colliculus (ICC) indicate that excitatory responses evoked by electrical stimulation of the lateral lemniscus consist of two components, an early, rapid response mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a later, a slower one mediated by N-methyl-D-aspartate (NMDA) receptors. The early response can be selectively blocked by AMPA receptor antagonists (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX]; or 6-cyano-7-nitroquinoxaline-2,3-dione) [CNQX], and the later one by NMDA receptor antagonists ((+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid [CPP]; or (+/-)-2-amino-5-phosphonovaleric acid) [APV]. Both AMPA and NMDA receptor-mediated responses can be elicited at resting potential, although the NMDA response is voltage dependent and makes a greater contribution when the cell membrane is depolarized. In vivo studies indicate that both AMPA and NMDA receptors contribute to sound-evoked responses. Both AMPA and NMDA receptor antagonists reduce the firing rate of single neurons in the ICC to contralaterally presented tones. Both classes of antagonist lower evoked activity over a wide range of sound intensities from threshold to maximum sound pressure levels. Thus, both NMDA and AMPA receptors contribute to responses over the full dynamic range of auditory sensitivity. The AMPA receptor antagonist, NBQX, is more effective than the NMDA receptor antagonist, CPP, in blocking responses of onset cells. Furthermore, NBQX and CPP have preferential effects in blocking the early or late responses of neurons that exhibited sustain activity to a 100 ms tone. Excitatory responses to sinusoidally amplitude-modulated stimuli are also reduced by application of either AMPA or NMDA antagonists. However, the synchrony of firing of action potentials to the modulation period (vector strength) is largely unaffected. The data suggest that the synchrony of firing of neurons in the inferior colliculus is determined primarily by the pattern of activity at lower levels of the auditory pathway and/or the local intrinsic properties of the cells.