Excitatory Response Area Research Articles

Frequency response areas of neurons in the mouse inferior colliculus. I. Threshold and tuning characteristics.

Excitatory and inhibitory frequency response areas of 130 neurons of the central nucleus of the mouse inferior colliculus (ICC) were mapped by extracellular single-unit recordings and quantitatively evaluated with regard to thresholds, steepness of slopes of excitatory tuning, characteristic frequencies of excitation (CF(E)), inhibition (CFI), and bandwidths of response areas (sharpness of tuning). Two-tone stimuli were used to determine the shapes of inhibitory response areas. Class I neurons (n=54) had asymmetrical (with regard to the CF(E)) excitatory and inhibitory response areas, with inhibition above CF(E) having lower thresholds and covering larger areas than inhibition below CF(E). Quantitative relationships between CF(E) and CF(I) thresholds, and sharpness of tuning showed that the receptive fields of about two-thirds of these neurons had properties similar to auditory nerve fibers. Class II neurons (n=36) had small symmetrical or tilted excitatory areas of rather constant bandwidths and broad inhibitory areas reaching far into and often through the excitatory area, leading to closed excitatory areas in ten neurons. Class III neurons (n=32) had higher excitatory thresholds and the highest proportions of unilateral inhibitory areas compared with neurons of the other classes. Their excitatory area often widened symmetrically with increasing sound level. Their inhibitory areas did not overlap with the excitatory area. Class IV neurons (n=8) had two branches of excitatory areas (two-CFs(E)) and six of the neurons had a central inhibitory area in addition to the low- and high-frequency inhibitory areas. In most neurons, the shapes of excitatory response areas predicted the shapes of inhibitory areas. Altogether, 15 neurons from all 4 classes had areas of facilitation in addition to inhibitory areas. Facilitation in six class IV neurons occurred between the two branches of the excitatory area. All 130 neurons had large inhibitory areas, 106 of them on both sides of the excitatory area. That is, sound processing in the ICC shows strong inhibitory components. The close relationships between excitatory and inhibitory CFs found here indicate that inhibitory projections to and interactions within the ICC are tonotopically organized comparable to the excitatory ones.

Acute spiral ganglion lesions change the tuning and tonotopic organization of cat inferior colliculus neurons

Many studies have reported plastic changes in central auditory frequency organization after chronic cochlear lesions. These studies employed mechanical, acoustic or drug-induced disruptions of restricted regions of the organ of Corti that permanently alter its tuning and sensitivity and require an extended recovery period before central effects can be measured. In this study, mechanical lesions were made to 1 mm sectors of the spiral ganglion (SG). These lesions remove a restricted portion of the cochlear output, but leave the organ of Corti and basilar membrane intact. Multiunit mapping assessed the pre- and post-lesion tonotopic organization of the inferior colliculus (IC). Immediately after SG lesions, IC neurons previously tuned to the lesion frequencies became less sensitive to those frequencies but more sensitive to lesion edge frequencies, resulting in a shift in their characteristic frequencies (CFs). Notches in the excitatory response areas at frequencies corresponding to the lesion frequencies and expansion of spatial tuning curves were also observed. CFs of neurons tuned to unlesioned frequencies were unchanged. These results suggest that ‘plastic’ changes similar to those observed after long survival times in previous studies require little or no experience and occur within minutes to hours following the lesion.

GABA-A antagonist causes dramatic expansion of tuning in primary auditory cortex.

Responses from 80 neurons in primary auditory cortex of anesthetized chinchillas were investigated before and during iontophoresis of bicuculline (BIC), a GABA-A antagonist. BIC caused a significant increase in the spontaneous discharge rate (SR) and driven firing rate in most neurons. Threshold decreased in many neurons and the excitatory response area expanded significantly above and below the neuron's characteristic frequency (CF). These results indicate that many neurons in primary auditory cortex receive excitatory inputs from a much broader frequency range than previously believed. GABA-A mediated inhibition can significantly alter the excitability and tuning of auditory cortex and could contribute significantly to cortical plasticity due to experience and cochlear pathology.

Facilitatory and inhibitory frequency tuning of combination-sensitive neurons in the primary auditory cortex of mustached bats.

Mustached bats, Pteronotus parnellii parnellii, emit echolocation pulses that consist of four harmonics with a fundamental consisting of a constant frequency (CF(1-4)) component followed by a short, frequency-modulated (FM(1-4)) component. During flight, the pulse fundamental frequency is systematically lowered by an amount proportional to the velocity of the bat relative to the background so that the Doppler-shifted echo CF(2) is maintained within a narrowband centered at approximately 61 kHz. In the primary auditory cortex, there is an expanded representation of 60.6- to 63. 0-kHz frequencies in the "Doppler-shifted CF processing" (DSCF) area where neurons show sharp, level-tolerant frequency tuning. More than 80% of DSCF neurons are facilitated by specific frequency combinations of approximately 25 kHz (BF(low)) and approximately 61 kHz (BF(high)). To examine the role of these neurons for fine frequency discrimination during echolocation, we measured the basic response parameters for facilitation to synthesized echolocation signals varied in frequency, intensity, and in their temporal structure. Excitatory response areas were determined by presenting single CF tones, facilitative curves were obtained by presenting paired CF tones. All neurons showing facilitation exhibit at least two facilitative response areas, one of broad spectral tuning to frequencies centered at BF(low) corresponding to a frequency in the lower half of the echolocation pulse FM(1) sweep and another of sharp tuning to frequencies centered at BF(high) corresponding to the CF(2) in the echo. Facilitative response areas for BF(high) are broadened by approximately 0.38 kHz at both the best amplitude and 50 dB above threshold response and show lower thresholds compared with the single-tone excitatory BF(high) response areas. An increase in the sensitivity of DSCF neurons would lead to target detection from farther away and/or for smaller targets than previously estimated on the basis of single-tone responses to BF(high). About 15% of DSCF neurons show oblique excitatory and facilitatory response areas at BF(high) so that the center frequency of the frequency-response function at any amplitude decreases with increasing stimulus amplitudes. DSCF neurons also have inhibitory response areas that either skirt or overlap both the excitatory and facilitatory response areas for BF(high) and sometimes for BF(low). Inhibition by a broad range of frequencies contributes to the observed sharpness of frequency tuning in these neurons. Recordings from orthogonal penetrations show that the best frequencies for facilitation as well as excitation do not change within a cortical column. There does not appear to be any systematic representation of facilitation ratios across the cortical surface of the DSCF area.

Single-unit responses in the inferior colliculus of decerebrate cats. I. Classification based on frequency response maps.

This study proposes a classification system for neurons in the central nucleus of the inferior colliculus (ICC) that is based on excitation and inhibition patterns of single-unit responses in decerebrate cats. The decerebrate preparation allowed extensive characterization of physiological response types without the confounding effects of anesthesia. The tone-driven discharge rates of individual units were measured across a range of frequencies and levels to map excitatory and inhibitory response areas for contralateral monaural stimulation. The resulting frequency response maps can be grouped into the following three populations: type V maps exhibit a wide V-shaped excitatory area and no inhibition; type I maps show a more restricted I-shaped region of excitation that is flanked by inhibition at lower and higher frequencies; and type O maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Units that produce a type V map typically have a low best frequency (BF: the most sensitive frequency), a low rate of spontaneous activity, and monotonic rate-level functions for both BF tones and broadband noise. Type I and type O units have BFs that span the cat's range of audible frequencies and high rates of spontaneous activity. Like type V units, type I units are excited by BF tones and noise at all levels, but their rate-level functions may become nonmonotonic at high levels. Type O units are inhibited by BF tones and noise at high levels. The existence of distinct response types is consistent with a conceptual model in which the unit types receive dominant inputs from different sources and shows that these functionally segregated pathways are specialized to play complementary roles in the processing of auditory information.

Processing of sinusoidally frequency modulated signals in the nuclei of the lateral lemniscus of the big brown bat, Eptesicus fuscus

Neurons in the nuclei of the lateral lemniscus (NLL) of the big brown bat, Eptesicus fuscus, show several distinctive patterns of response to unmodulated tones. Previous work suggests that sustained responders are specialized to transmit information about sound level and duration while onset responders transmit precise timing information. The biosonar signals of E. fuscus consist of multiple, downward frequency modulated sweeps that change in slope and repetition rate as the bat approaches a target. An obvious hypothesis would be that NLL neurons with sustained responses should discharge during the time when the frequency of a signal is within their response area, but that onset responders should discharge each time the frequency enters the excitatory portion of their response area. In this study we examined the responses of NLL neurons to sinusoidally frequency modulated (SFM) signals presented monaurally to awake, restrained bats. Extracellular recordings were obtained from single neurons in the multipolar and columnar divisions of the ventral nucleus (VNLLm and VNLLc), the intermediate nucleus (INLL) and the dorsal nucleus of the lateral lemniscus (DNLL). All NLL neurons responded synchronously to SFM signals under some conditions. The temporal precision of synchronization was quantified using a coefficient of synchronization (CS), where a value of 1 equals perfect synchrony. Maximum CS values ranged from 0.70 to >0.99, were generally highest at low modulation rates (<200 Hz), and showed lowpass characteristics for modulation rate. The maximal modulation rates that elicited synchronous discharge ranged from 50 to 500 Hz. The highest maximal rates were found in the VNLLm and VNLLc, the lowest in DNLL. The ability of NLL neurons to synchronize their discharge to the pattern of an SFM signal is intermediate between that of neurons in the cochlear nucleus and in the inferior colliculus. For the majority of neurons in VNLLm, INLL and DNLL, the precision of synchronization was approximately equal for the downward and upward components of the SFM signal; in contrast, 69% of VNLLc neurons responded selectively to the downward component of the SFM signal. All VNLLc neurons and a subset of those in VNLLm, INLL, and DNLL responded synchronously to SFM signals only if the frequency excursions included a border of the excitatory frequency bandwidth, suggesting that the synchronous discharge was due primarily to the repeated passage of the stimulus frequency into and out of the excitatory portion of the response area. In the case of VNLLc neurons, only the high frequency border was effective. Other neurons, especially those in DNLL, responded synchronously to SFM signals with frequency excursions that were confined entirely within the excitatory response area.

Functional specialization in auditory cortex: responses to frequency-modulated stimuli in the cat's posterior auditory field.

The mammalian auditory cortex contains multiple fields but their functional role is poorly understood. Here we examine the responses of single neurons in the posterior auditory field (P) of barbiturate- and ketamine-anesthetized cats to frequency-modulated (FM) sweeps. FM sweeps traversed the excitatory response area of the neuron under study, and FM direction and the linear rate of change of frequency (RCF) were varied systematically. In some neurons, sweeps of different sound pressure levels (SPLs) also were tested. The response magnitude (number of spikes corrected for spontaneous activity) of nearly all field P neurons varied with RCF. RCF response functions displayed a variety of shapes, but most functions were of low-pass characteristic or peaked at rather low RCFs (<100 kHz/s). Neurons with strong responses to high RCFs (high-pass or nonselective RCF response function characteristics) all displayed spike count-SPL functions to tone burst onsets that were monotonic or weakly nonmonotonic. RCF response functions and best RCFs often changed with SPL. For most neurons, FM directional sensitivity, quantified by a directional sensitivity (DS) index, also varied with RCF and SPL, but the mean and width of the distribution of DS indices across all neurons was independent of RCF. Analysis of response timing revealed that the phasic response of a neuron is triggered when the instantaneous frequency of the sweep reaches a particular value, the effective Fi. For a given neuron, values of effective Fi were independent of RCF, but depended on FM direction and SPL and were associated closely with the boundaries of the neuron's frequency versus amplitude response area. The standard deviation (SD) of the latency of the first spike of the response decreased with RCF. When SD was expressed relative to the rate of change of stimulus frequency, the resulting index of frequency jitter increased with RCF and did so rather uniformly in all neurons and largely independent of SPL. These properties suggest that many FM parameters are represented by, and may be encoded in, orderly temporal patterns across different neurons in addition to the strength of responses. When compared with neurons in primary and anterior auditory fields, field P neurons respond better to relatively slow FMs. Together with previous studies of responses to modulations of amplitude, such as tone onsets, our findings suggest more generally that field P may be best suited for processing signals that vary relatively slowly over time.

Aspects of Temporal Processing of FM Stimuli in Primary Auditory Cortex

The timing of the phasic responses of neurons in cat primary auditory cortex to linear frequency modulated (FM) sweeps was studied and compared in detail with the neurons-responses to tone bursts of different frequencies. FM sweeps differed in direction and rate of change of frequency (RCF) and entirely traversed the neuron's excitatory frequency response area. It is demonstrated that a neuron's response to FM sweeps in a given direction is initiated whenever the instantaneous frequency of the sweep reaches a particular value, the effective Fi, independent of RCF. Effective Fi for upward and downward sweeps are closely associated with the steepest slopes of the neuron's tone burst frequency response function below and above the best frequency, respectively. This predictability of response timing appears ideal for encoding of FM parameters, such as direction, RCF, and form of modulation (e.g. linear, exponential) in the spatiotemporal pattern of excitation and in the inter-response-intervals of different neurons, i.e. in latency place codes.

GABA inputs control discharge rate primarily within frequency receptive fields of inferior colliculus neurons.

1. Recent studies have suggested that gamma-aminobutyric acid (GABA) inputs shape monaural and binaural neuronal response properties in the central nucleus of the inferior colliculus (CIC). CIC neurons receive major inhibitory GABAergic projections from intrinsic, commissural, and extrinsic sources. Many GABAergic projections now are thought to arise from cells that are tonotopically matched to their CIC targets. 2. We tested the hypothesis that GABA circuits are aligned primarily within the CIC target neuron's excitatory response area and therefore have their greatest effects on discharge rate mainly within that frequency domain. GABA inhibition was examined by recording families of isointensity contours before, during, and after GABAA receptor blockade. Iontophoretic application of bicuculline-methiodide (BMI) was used to block GABAA receptors. Quantitative measures of frequency bandwidth and z-score analysis of discharge rate within the excitatory receptive field were used to compare pre- and postdrug conditions. 3. Chinchilla CIC unit response properties were similar to those described for other species, with a high percentage of phasic temporal response patterns and nonmonotonic rate-intensity functions in response to monaural contralateral characteristic frequency (CF) tones. Binaural responses of most CIC neurons showed suppression of contralaterally evoked responses by ipsilateral stimulation. 4. For 85% of CIC neurons, blockade of GABAA inputs was found to increase discharge rate within the excitatory response area. Forty-five percent were classified as near-CF changes and 32% as near-CF and low side. Changes in lateral/flanking inhibition in the absence of near-CF changes were never observed. Forty-one percent of CIC neurons displayed less than a 10% increase in frequency bandwidth at 25-35 dB above threshold with BMI application. 5. These data suggest that GABA inhibition arises primarily from neurons with inhibitory fields aligned with their CIC targets. Thus the effect of the inhibition is primarily contained within or overlapping each target neuron's excitatory response area. CIC GABAergic circuits may function to adjust the gain needed for coding complex signals over a wide dynamic range.

Plasticity of response properties of inferior colliculus neurons following acute cochlear damage.

1. The discharge patterns of 40 neurons in the central nucleus of the inferior colliculus (ICC) of the chinchilla were evaluated before and after acute cochlea trauma from intense tone exposure. Single-unit recordings were obtained from neurons in the ICC contralateral to the sound-stimulated ear. Cochlear trauma was induced with a short-duration (15-25 min), high-intensity pure tone (95-115 dB SPL) at a frequency above the neuron's characteristic frequency (CF). The aim of the traumatizing exposure was to damage the peripheral sensory receptors associated with frequencies above the neuron's CF. The damage was expected to attenuate inputs to the neural circuits responsible for activating the inhibitory sidebands above CF. 2. Three types of frequency-threshold tuning curves were observed before the exposure: 1) open V tuning curves (55%) that became wider as sound intensity increased; 2) level-tolerant tuning curves (37.5%) that maintained a very narrow bandwidth even at high sound intensities; and 3) upper-threshold tuning curves (7.5%) in which excitatory responses were elicited at low and moderate intensities, but not at high intensities. The traumatizing exposure caused a dramatic widening of level-tolerant (80% of sample) and upper-threshold tuning curves (100% of sample) at high sound intensities but caused almost no change in the low-threshold tip of the tuning curves. By contrast, tuning curves with an open V configuration were generally unaffected (approximately 90% of sample) by the traumatizing exposure. 3. Discharge rate-level functions in the ICC were of two general types: 1) strongly nonmonotonic (60%) or 2) saturating, monotonic (40%). The traumatizing exposure caused a significant increase in the suprathreshold discharge rates in 70% of all neurons studied. Among the neurons with strongly nonmonotonic discharge rate-level functions, 93% showed a significant increase in discharge rate. 4. The poststimulus time histograms (PSTH) to tone bursts were of three main types: 1) onset, 2) pauser, and 3) sustained responders. The traumatizing exposure had almost no effect on the PSTH of onset or sustained responders. However, pause PSTH frequently (75%) showed a significant decrease in the pause duration and an increase in the sustained discharge rate following the pause after the exposure. 5. The results suggest that the response properties of neurons with extremely narrow tuning curves and nonmonotonic discharge rate-level functions are shaped by an inhibitory circuit that is activated by frequencies above the high-frequency flank of the tuning curve. This inhibitory circuit modifies the excitatory response in the following ways: 1) it narrows the excitatory response area at suprathreshold intensities particularly at frequencies below CF, 2) it alters the shape of the discharge rate-level function by suppressing the discharge rates at suprathreshold intensities, and 3) it modifies the temporal discharge pattern of the pause PSTH by suppressing neural activity that occurs after the onset response. The effects of these inhibitory inputs can be reduced (disinhibition) by damaging the sensory cells in the inner ear that activate this circuit. The exact locus of the inhibitory circuit(s) is unknown but may involve inhibitory inputs located at the level of the cochlear nucleus and/or at levels up to the inferior colliculus.

Monaural inhibition in cat auditory cortex

1. Several studies of auditory cortex have examined the competitive inhibition that can occur when appropriate sounds are presented to each ear. However, most cortical neurons also show both excitation and inhibition in response to presentation of stimuli at one ear alone. The extent of such inhibition has not been described. Forward masking, in which a variable masking stimulus was followed by a fixed probe stimulus (within the excitatory response area), was used to examine the extent of monaural inhibition for neurons in primary auditory cortex of anesthetized cats (barbiturate or barbiturate-ketamine). Both the masking and probe stimuli were 50-ms tone pips presented to the contralateral ear. Most cortical neurons showed significant forward masking at delays beyond which masking effects in the auditory nerve are relatively small compared with those seen in cortical neurons. Analysis was primarily concerned with such components. Standard rate-level functions were also obtained and were examined for nonmonotonicity, an indication of level-dependent monaural inhibition. 2. Consistent with previous reports, a wide range of frequency tuning properties (excitatory response area shapes) was found in cortical neurons. This was matched by a wide range of forward-masking-derived inhibitory response areas. At the most basic level of analysis, these were classified according to the presence of lateral inhibition, i.e., where a probe tone at a neuron's characteristic frequency was masked by tones outside the limits of the excitatory response area. Lateral inhibition was a property of 38% of the sampled neurons. Such neurons represented 77% of those with nonmonotonic rate-level functions, indicating a strong correlation between the two indexes of monaural inhibition; however, the shapes of forward masking inhibitory response areas did not usually correspond with those required to account for the "tuning" of a neuron. In addition, it was found that level-dependent inhibition was not added to by forward masking inhibition. 3. Analysis of the discharges to individual stimulus pair presentations, under conditions of partial masking, revealed that discharges to the probe occurred independently of discharges to the preceding masker. This indicates that even when the masker is within a neuron's excitatory response area, forward masking is not a postdischarge habituation phenomenon. However, for most neurons the degree of masking summed over multiple stimulus presentations appears determined by the same stimulus parameters that determine the probability of response to the masker.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibitory inputs modulate discharge rate within frequency receptive fields of anteroventral cochlear nucleus neurons

1. The amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glycine function as inhibitory neurotransmitters associated with nonprimary inputs onto spherical bushy and stellate cells, two principal cell types located in the anteroventral cochlear nucleus (AVCN). These neurons are characterized by primary-like (including phase-locked) and chopper temporal response patterns, respectively. 2. Inhibition directly adjacent to the excitatory response area has been hypothesized to sharpen or limit the breadth of the tonal frequency receptive field. This study was undertaken to test whether GABA and glycine circuits function primarily to sharpen the lateral edges of the tonal excitatory response area or to modulate discharge rate within central portions of the excitatory response area of AVCN neurons. 3. To test this, iontophoretic application of the glycineI antagonist, strychnine, or the GABAA antagonist, bicuculline, was used to block inhibitory inputs after obtaining control families of isointensity contours (response areas) from extracellularly recorded AVCN neurons. 4. Blockade of GABA and/or glycine inputs was found to increase discharge rate primarily within the excitatory response area of neurons displaying chopper and primary-like temporal responses with little or no change in bandwidth or in off-characteristic frequency (CF) discharge rate. 5. The principal sources of inhibitory inputs onto AVCN neurons are cells located in the dorsal cochlear nucleus and superior olivary complex, which appear to be tonotopically matched to their targets. In agreement with these morphological studies, the data presented in this paper suggest that most GABA and/or glycine inhibition is tonotopically aligned with excitatory inputs. 6. These findings support models that suggest that GABA and/or glycine inputs onto AVCN neurons are involved in circuits that adjust gain to enable the detection of signals in noise by enhancing signal relative to background.

Functional changes in the ventral cochlear nucleus following acute acoustic overstimulation.

The effects of acute acoustic overstimulation on the discharge patterns of neurons in the ventral cochlear nucleus (VCN) were evaluated in anesthetized chinchillas. Response measures were obtained from the same neuron before and after presenting a 3- to 5-min intense tone (90-105 dB SPL) located one-half oct above the unit's characteristic frequency (CF). If a unit had an inhibitory response area at frequencies above CF and if the traumatizing tone reduced the magnitude of the inhibitory response, then the neuron's discharge rate to suprathreshold tones at CF increased ("enhancement") by as much as 25%. However, if a unit lacked an inhibitory response area at frequencies above CF, then the traumatizing tone typically caused either no change or a decrease in the unit's discharge rate at CF. The traumatizing tone did not alter the shape of the post-stimulus time histograms. Moreover, the width of the excitatory response area was not altered by the exposure even when traumatizing stimulus reduced the magnitude of the inhibitory response above CF. The enhanced firing rate at CF following the exposure could conceivably contribute to the enhanced evoked-potential amplitudes observed in the auditory brain stem following acoustic trauma.

Response properties in young and old Fischer-344 rat lateral superior olive neurons: A quantitative approach

Significant age-related functional deficits may result from a selective loss of inhibitory processing in the lateral superior olivary (LSO) nucleus. To test this hypothesis, methods were developed for quantitative comparisons of the excitation evoked by ipsilateral acoustic stimuli and the inhibition evoked by contralateral acoustic stimuli in neurons recorded from this binaural structure. Data were obtained from 103 LSO neurons from 22 young adult (3–6 month) and 70 LSO neurons from 14 old (20–23 month) Fischer-344 (F-344) rats. Age-related increases in the thresholds of auditory brainstem responses as well as in the inhibitory and excitatory responses of LSO neurons were observed. Spike-discharge rates were analyzed using multiple regression analysis for interaural intensity data and by calculating correlation coefficients between excitatory and inhibitory isointensity curves. Most LSO principal cells exhibited ipsilateral excitation and contralateral inhibition of similar strength for similar stimuli. Inhibitory and excitatory response areas of these neurons were similar based on visual inspection and correlation coefficients. No statistically significant age-related changes were observed for (a) rate-level functions generated by ipsilateral or contralateral stimuli; (b) maximal discharge rate; (c) conduction latencies; or (d) measures of binaural function. However, a small percentage of LSO neurons both in young and old rats displayed “unmatched” inhibitory and excitatory response areas. Quantitative methods developed in this study are used to examine age-related changes in binaural function in the inferior colliculus of F-344 rats and in the LSO of the Sprague-Dawley rat. Although no asymmetrical aging changes were observed for the F-344 rat LSO, there appear to be significant differences between the aging auditory system in the F-344 and Sprague-Dawley rats. Age-related changes have been previously described for the F-344 in other brainstem auditory structures.

Sensitivity of neurons in cat primary auditory cortex to tones and frequency-modulated stimuli. I: Effects of variation of stimulus parameters

In the primary auditory cortex (AI) of barbiturate-anesthetized cats multi-unit responses to tones and to frequency-modulated (FM) tonal stimuli were analyzed. Characteristic frequency (CF), sharpness of tuning, minimum threshold, and dynamic range of spike count — intensity functions were determined. Minimum threshold and dynamic range were positively correlated. The response functions to unidirectional FM sweeps of varying linear rate of change of frequency (RCF) that traversed the excitatory frequency response areas (FRAs) displayed a variety of shapes. Preferences for fast RCFs (> 1000 kHz/s) were most common. Best RCF was not correlated with measures of sharpness of tuning. Directional preference and sensitivity were quantified by a DS index which varied with RCF. About two-thirds of the multi-unit responses showed a preference for downward sweeps. Directional sensitivity was independent of CF and independent of best RCF. Measurements of latencies of phasic responses to unidirectional FM sweeps of different RCF demonstrated that the discharges of a given multi-unit over its effective RCF range were initiated at the same instantaneous frequency (effective F i), independent of RCF. Effective F iS fell within the excitatory FRA of a given multi-unit. The relationships of effective F iS to CF show that responses were evoked only when the frequency of the signal was modulated towards CF and not when modulated away from it, and that responses were initiated before the modulation reached CF. Changes in the range and depth of modulation had only minor, if any, effects on RCF response characteristics, FM directional sensitivity, and effective F iS, as long as the beginning and ending frequencies of FM sweeps fell outside a multi-unit's FRA. Stimulus intensity also had only moderate effects on RCF response characteristics and DS. However, effective F iS were influenced in systematic fashions: with increases in intensity, effective F iS to upward and downward sweeps decreased and increased, respectively. Thus, for higher intensities FM responses were initiated at instantaneous frequencies occuring earlier in the signal. The results are compared with previous data on tone and FM sensitivity of auditory neurons in cortical and subcortical structures, and mechanisms of FM rate and directional sensitivity are discussed. The topographic representations of these neuronal properties in AI are reported in the companion report.

GABAA receptor antagonist bicuculline alters response properties of posteroventral cochlear nucleus neurons.

1. The role of GABAergic inhibitory inputs onto posteroventral cochlear nucleus (PVCN) neurons in the anesthetized chinchilla was investigated through iontophoretic application of the GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline. The majority of the neurons studied displayed phasic temporal response patterns. 2. All the neurons were sensitive to bicuculline and displayed an increase in discharge rate, which was greatest during the post-onset portion of the response. Most of the tested neurons were also sensitive to muscimol, which appeared to mimic the putative effect of endogenous GABA. 3. Bicuculline reduced the average first-spike latency and the average variability of the first-spike latency. Muscimol had the opposite effect. 4. Bicuculline did not significantly alter the threshold but rather increased discharge rate at suprathreshold intensities. 5. The width of the excitatory response area was not significantly increased by application of bicuculline. The increase in discharge rate occurred within the units' excitatory response areas. 6. The shape of the rate-intensity functions was not altered by bicuculline application. 7. We conclude that GABAergic inhibitory inputs control the post-onset discharge rate of some PVCN neurons. They may suppress tonic activity, resulting in more phasic discharge patterns.

Multiplicity of inputs in the afferent path to cat auditory cortex neurons revealed by tone-on-tone masking.

This report presents preliminary evidence on the effect of continuous tonal maskers on the responses of single primary auditory cortical neurons in anesthetized cats to tonal signals across their effective frequency ranges 10 dB above characteristic frequency threshold. Tonal maskers had three kinds of effects. In many cells, the masker produced a generalized suppression of responses to tones across the response area. In some neurons, typically those with monotonic intensity profiles, tonal maskers on one side of the response area produced a selective suppression of responses to tone signals on the same side as the masker. This differential sensitivity to the masker is evidence of independent inputs to those neurons on the high- and low-frequency sides of their excitatory response areas. Finally, in non-monotonic neurons, tonal maskers at the high-frequency edge of the excitatory response area produced enhanced responses to tonal signals on the same side of the response area as the masker. We interpret this as a release from the effect of an inhibitory input located at the high-frequency edge of the response area.

Auditory cortical neurons are sensitive to static and continuously changing interaural phase cues

1. The interaural-phase-difference (IPD) sensitivity of single neurons in the primary auditory (AI) cortex of the anesthetized cat was studied at stimulus frequencies ranging from 120 to 2,500 Hz. Best frequencies of the 43 AI cells sensitive to IPD ranged from 190 to 2,400 Hz. 2. A static IPD was produced when a pair of low-frequency tone bursts, differing from one another only in starting phase, were presented dichotically. The resulting IPD-sensitivity curves, which plot the number of discharges evoked by the binaural signal as a function of IPD, were deeply modulated circular functions. IPD functions were analyzed for their mean vector length (r) and mean interaural phase (phi). Phase sensitivity was relatively independent of best frequency (BF) but highly dependent on stimulus frequency. Regardless of BF or stimulus frequency within the excitatory response area the majority of cells fired maximally when the ipsilateral tone lagged the contralateral signal and fired least when this interaural-phase relationship was reversed. 3. Sensitivity to continuously changing IPD was studied by delivering to the two ears 3-s tones that differed slightly in frequency, resulting in a binaural beat. Approximately 26% of the cells that showed a sensitivity to static changes in IPD also showed a sensitivity to dynamically changing IPD created by this binaural tonal combination. The discharges were highly periodic and tightly synchronized to a particular phase of the binaural beat cycle. High synchrony can be attributed to the fact that cortical neurons typically respond to an excitatory stimulus with but a single spike that is often precisely timed to stimulus onset. A period histogram, binned on the binaural beat frequency (fb), produced an equivalent IPD-sensitivity function for dynamically changing interaural phase. For neurons sensitive to both static and continuously changing interaural phase there was good correspondence between their static (phi s) and dynamic (phi d) mean interaural phases. 4. All cells responding to a dynamically changing stimulus exhibited a linear relationship between mean interaural phase and beat frequency. Most cells responded equally well to binaural beats regardless of the initial direction of phase change. For a fixed duration stimulus, and at relatively low fb, the number of spikes evoked increased with increasing fb, reflecting the increasing number of effective stimulus cycles. At higher fb, AI neurons were unable to follow the rate at which the most effective phase repeated itself during the 3 s of stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

GABAergic inhibition upon auditory response properties of neurons in the dorsal cochlear nucleus of the rat

It is well known that the superficial layers of the dorsal cochlear nucleus (DCN) are rich in GABAergic neurons. We investigated the effects of topical application of GABA receptor agonists and/or antagonists upon the auditory response properties of DCN neurons in rats anesthetized with alpha chloralose-urethane. Auditory stimuli consisted of 20 ms tone bursts presented in a free field. Response properties of DCN neurons were studied before and during iontophoretic application of GABA, bicuculline methiodide (BIC) and muscimol (MUS) alone and GABA with MUS or BIC through triple barrel electrodes glued to the recording microelectrode. Of 68 DCN neurons studied, 27 were sensitive to topical application of the GABA agonists or antagonist. In these neurons, BIC enhanced spontaneous activity as well as auditory responses and decreased the Q-30 quality factor values. MUS reduced auditory responses. BIC often increased the width of the turning curve but GABA and/or MUS reduced it. Without drug application, GABA sensitive neurons tended to have longer response latencies and larger tuning widths at 30 dB above threshold as well as larger Q-30 values as compared with neurons that were insensitive to GABA. These findings suggest that: 1) GABAergic neurons determine the width of the tuning curve in neurons with GABA receptors by curtailing the excitatory response area, and 2) such neurons receive tonic inhibition from intrinsic GABAergic neurons.

Spectral response patterns of auditory cortex neurons to harmonic complex tones in alert monkey (Macaca mulatta)

1. The auditory cortex in the superior temporal region of the alert rhesus monkey was explored for neuronal responses to pure and harmonic complex tones and noise. The monkeys had been previously trained to recognize the similarity between harmonic complex tones with and without fundamentals. Because this suggested that they could preceive the pitch of the lacking fundamental similarly to humans, we searched for neuronal responses relevant to this perception. 2. Combination-sensitive neurons that might explain pitch perception were not found in the surveyed cortical regions. Such neurons would exhibit similar responses to stimuli with similar periodicities but differing spectral compositions. The fact that no neuron with responses to a fundamental frequency responded also to a corresponding harmonic complex missing the fundamental indicates that cochlear distortion products at the fundamental may not have been responsible for missing fundamental-pitch perception in these monkeys. 3. Neuronal responses can be expressed as relatively simple filter functions. Neurons with excitatory response areas (tuning curves) displayed various inhibitory sidebands at lower and/or higher frequencies. Thus responses varied along a continuum of combined excitatory and inhibitory filter functions. 4. Five elementary response classes along this continuum are presented to illustrate the range of response patterns. 5. "Filter (F) neurons" had little or no inhibitory sidebands and responded well when any component of a complex tone entered its pure-tone receptive field. Bandwidths increased with intensity. Filter functions of these neurons were thus similar to cochlear nerve-fiber tuning curves. 6. "High-resolution filter (HRF) neurons" displayed narrow tuning curves with narrowband widths that displayed little growth with intensity. Such cells were able to resolve up to the lowest seven components of harmonic complex tones as distinct responses. They also responded well to wideband stimuli. 7. "Fundamental (F0) neurons" displayed similar tuning bandwidths for pure tones and corresponding fundamentals of harmonic complexes. This response pattern was due to lower harmonic complexes. This response pattern was due to lower inhibitory sidebands. Thus these cells cannot respond to missing fundamentals of harmonic complexes. Only physically present components in the pure-tone receptive field would excite such neurons. 8. Cells with no or very weak responses to pure tones or other narrowband stimuli responded well to harmonic complexes or wideband noise.(ABSTRACT TRUNCATED AT 400 WORDS)