EI Neurons Research Articles

Mechanisms underlying azimuth selectivity in the auditory cortex of the pallid bat

This study focused on mechanisms underlying azimuth selectivity in the primary auditory cortex (A1) of pallid bats. The pallid bat listens to prey-generated noise (5–35 kHz) to localize and hunt terrestrial prey. The region of A1 tuned between 5 and 35 kHz consists of two clusters of neurons distinguished by interaural intensity difference (IID) selectivity: binaurally inhibited (EI) and peaked. The first aim of this study was to use sequential dichotic/free-field stimulation to test the hypothesis that IID is the primary cue underlying azimuth selectivity in neurons tuned in the prey-generated noise frequency band. IID selectivity and ear directionality at the neuron's characteristic frequency (CF) were used to predict azimuth selectivity functions. The predicted azimuth selectivity was compared with the actual azimuth selectivity from the same neurons. Prediction accuracy was similarly high for EI neurons and peaked neurons with low CF, whereas predictions were increasingly inaccurate with increasing CF among the peaked neurons. The second aim of this study was to compare azimuth selectivity obtained with noise and CF tones to determine the extent to which stimulus bandwidth influences azimuth selectivity in neurons with different binaural properties. The azimuth selectivity functions were similar for the two stimuli in the majority of EI neurons. A greater percentage of peaked neurons showed differences in their azimuth selectivity for noise and tones. This included neurons with multiple peaks when tested with tones and a single peak when tested with noise. Taken together, data from the two aims suggest that azimuth tuning of EI neurons is primarily dictated by IID sensitivity at CF. Peaked neurons, particularly those with high CF, may integrate IID sensitivity across frequency to generate azimuth selectivity for broadband sound. The data are consistent with those found in cat and ferret A1 in that binaurally facilitated neurons depend to a greater extent (compared to EI neurons) on spectral integration of binaural properties to generate azimuth selectivity for broadband stimuli.

Conditioned enhancement and suppression in the developing auditory midbrain.

Neural responses in the adult central auditory system to binaural stimuli can be altered by preceding acoustic events, including auditory motion. To determine whether the juvenile auditory system also exhibits this feature, we have examined interaural level difference (ILD) processing in the developing gerbil. A long binaural stimulus was followed without interruption by modulation of the level difference (virtual acoustic motion), which in turn was followed smoothly by a new steady state ILD. Auditory responses of single neurons in the inferior colliculus (IC) were assessed for sensitivity to the final steady state ILD. The response of EI neurons (excited by contralateral stimulation and inhibited ipsilaterally) was examined at postnatal (P) days 17-18, P24-25, and in adult animals. In adult animals, a sudden reduction of the inhibitory stimulus level resulted in a long-lasting (median = 4.3 s) enhanced discharge rate (conditioned enhancement). In P17-18 animals, conditioned enhancement only lasted for 1.2 s. When the inhibitory stimulus level was suddenly increased, adult neurons often displayed a conditioned suppression of discharge rate (median = 4.5 s), whereas P17-18 neurons remained suppressed for a much briefer period (median = 1.2 s). Moreover, the difference between conditioned responses and control discharge rates was three-four times greater in adult neurons compared to those recorded in P17-25 animals. Because conditioned responses are sensitive to the relative balance of contralateral excitation and ipsilateral inhibition, we examined the relationship between excitatory and inhibitory thresholds. In adult animals, excitatory thresholds were an average of 12 dB lower than inhibitory thresholds, while at P17-25 excitatory and inhibitory thresholds were roughly the same. These results indicate that computational properties of juvenile and adult IC neurons differ quantitatively, and this may reflect an imbalance between excitation and inhibition. The developmental differences described herein may limit the ability of young animals to locate a sound source with the latency and accuracy of an adult.

Responses of neurons in the inferior colliculus of the rat to interaural time and intensity differences in transient stimuli: Implications for the latency hypothesis

Although the sensitivity to interaural intensity differences (IIDs) of neurons receiving excitatory — inhibitory binaural input (EI neurons) has been examined in numerous studies, the mechanisms underlying this sensitivity remain unclear. According to the ‘latency hypothesis’, neuronal sensitivity to IIDs reflects sensitivity to differences in the timing of ipsilateral and contralateral inputs that are produced as a consequence of the effects of intensity upon latency. If the latency hypothesis is correct, a neuron's responses over any given IID range should be predicted by its responses to the interaural time differences (ITDs) that are ‘equivalent’ to the IIDs tested, in the sense that they produce the same changes in the relative timing of inputs. This prediction from the latency hypothesis was examined by determining the sensitivity of EI neurons in the inferior colliculus of anesthetized rats to IIDs and ITDs in click stimuli, under conditions that allowed ‘equivalent’ ITDs to be estimated. In approximately 10% of the 41 neurons tested, the IID-sensitivity function was a perfect or near-perfect match to the equivalent-ITD function, indicating that IID sensitivity could be entirely accounted for in terms of sensitivity to intensity-produced neural time differences, as asserted by the latency hypothesis. For the majority of neurons, however, sensitivity to equivalent ITDs accounted only partially for the characteristics of the IID-sensitivity function; other features of the function in these cases appeared to reflect the operation of an additional factor, most probably the relative magnitude of the inputs from the two ears. Although the conclusions are qualified by the fact that one of the assumptions on which the estimation of equivalent ITDs was based was probably not satisfied for some neurons, the results suggest that intensity-produced changes in both the magnitude and the timing of excitatory and inhibitory inputs shape the IID sensitivity of most EI neurons.

Binaural processing in the dorsal nucleus of the lateral lemniscus

We studied the binaural properties of 72 neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the mustache bat. There are six main findings: 1) Conventional EI neurons that were excited by stimulation of the contralateral ear and inhibited by ipsilateral stimulation, comprise the majority (80%) of binaural DNLL cells. 2) For most EI neurons the quantitative features of their interaural intensity disparity (IID) functions, maximum inhibition, dynamic range and 50% point IIDs, were largely unaffected by the absolute intensity at the contralateral ear. 3) Although the net effect of the inhibition evoked by ipsilateral stimulation was to suppress discharges evoked by contralateral stimulation, our results indicate that the inhibitory inputs can act in three different ways. The first was a time-intensity trade, where increasing the intensity at the ipsilateral ear evoked inhibitory effects with progressively shorter latencies. The second way was that the latency of inhibition did not appear to decrease with ipsilateral intensity, but rather increasing ipsilateral intensity appeared only to increase the strength of the inhibition. The third way was that the lowest effective ipsilateral intensity suppressed the first spikes evoked by the contralateral stimulus and higher ipsilateral intensities then suppressed the later discharges of the train. Each of these inhibitory patterns was seen in about a third of the cells. 4) Neurons that had more complex binaural properties, such as the facilitated EI neurons (EI/F) and neurons that were driven by sound to either ear (EE neurons), represented about 20% of the binaural population. There were two types of EE neurons; those in which there was a simple summation of discharges evoked with certain IIDs, and those in which the spike-counts to binaural stimulation at certain IIDs were greater than a summation of the monaural counts and thus were facilitated. 5) All binaural neurons were strongly inhibited with IIDs that favored the ipsilateral ear. Our findings indicate that the more complex binaural types, the facilitated EI neurons (EI/F) as well as the two types of EE neurons, may be constructed from conventional EI neurons by adding inputs from several sources that impart the more complex features to these neurons. We propose four circuits that could account for the different binaural response properties that we observed. The circuits are based on the known connections of the DNLL and the neurochemistry of those connections. Finally, we compared the binaural properties of neurons in the mustache bat DNLL with those of neurons in the mustache bat inferior colliculus and lateral superior olive. The comparative features suggest that the processing of the interaural intensity disparities undergoes at least four types of response transformations along the ascending auditory system.

GABA shapes sensitivity to interaural intensity disparities in the mustache bat's inferior colliculus: implications for encoding sound location

This study examined how GABAergic inhibition affected binaural properties of neurons in the mustache bat's inferior colliculus. Evaluations were made by documenting changes in acoustically evoked inhibition that occurred when GABAergic inputs were reversibly blocked by iontophoretic application of the GABAA antagonist bicuculline. We studied neurons sensitive to interaural intensity disparities (IIDs), since these are the principal cues animals use to localize high-frequency sounds. Neurons sensitive to these cues receive excitation from one ear and inhibition from the other ear, and are called EI neurons. Recordings focused on the EI region in the hypertrophied 60 kHz isofrequency contour, where the sensitivities of the EI cells to IIDs are systematically ordered, thereby creating a map of IID sensitivity. EI neurons were classified on the basis of their IID functions, of which there were two principal types. Seventy percent of the cells had conventional IID functions where the firing rate evoked by a fixed intensity at the contralateral (excitatory) ear remained constant with low intensities at the ipsilateral (inhibitory) ear and then declined progressively as the intensity at the ipsilateral ear increased. We refer to cells that had this type of IID function simply as EI neurons. The IID functions in the remaining 30% of the cells showed binaural facilitation and were classified as EI/f neurons. In these cells, increasing sound intensity at the ipsilateral (inhibitory) ear when the intensity at the contralateral (excitatory) ear was fixed, initially caused the firing rate to increase by at least 25% above the rate evoked by the sound at the contralateral ear alone. Additional intensity increases at the ipsilateral ear then resulted in a marked decline in response rate. We examined the effects of bicuculline on three binaural properties: (1) the degree of inhibition evoked by the ipsilateral ear (the maximum inhibition), (2) the IID at which the unit's discharge rate declined by 50% (the 50% point), and (3) binaural facilitation. There are three main findings. First, bicuculline substantially reduced or eliminated the inhibition evoked by the ipsilateral ear in about 40% of the cells. In the other 60% of the cells, bicuculline had little or no effect on the magnitude of the ipsilaterally evoked inhibition. The second finding is that in more than half of the cells in which there was little or no reduction in the magnitude of the ipsilaterally evoked inhibition, bicuculline changed the IID at which the ipsilaterally evoked inhibition caused the discharge rate to decline by 50%.(ABSTRACT TRUNCATED AT 400 WORDS)

Binaural interaction in high-frequency neurons in inferior colliculus of the cat: effects of variations in sound pressure level on sensitivity to interaural intensity differences

1. Development of models of the manner in which interaural intensity differences (IIDs), the major binaural cue for the azimuthal location of high-frequency sounds, are coded by populations of neurons requires knowledge of the extent to which the IID sensitivity of individual neurons is invariant with changes in sound pressure level (SPL) and other stimulus parameters. To examine this tissue, recordings were obtained from a large sample (n = 458) of neurons with characteristic frequency (CF) greater than 3 kHz in the central nucleus of the inferior colliculus (ICC) of anesthetized cats. The sensitivity to IIDs and the effects of changes in SPL on this sensitivity were examined in neurons receiving excitatory contralateral input and inhibitory or mixed inhibitory/facilitatory ipsilateral input (EI neurons). 2. The form of an EI neuron's IID sensitivity and the effects of changes in SPL on that sensitivity were found to be determined in part by the characteristics of the neuron's rate-intensity function for monaural contralateral stimulation, and detailed rate-intensity functions were therefore obtained for 91 neurons. Many ICC neurons have nonmonotonic rate-intensity functions, the proportion so classified depending on the criterion of nonmonotonicity employed. 3. IID sensitivity functions for CF tonal stimuli were obtained at one or more intensities for 90 neurons, using a method of generating IIDs that kept the average binaural intensity (ABI) of the stimuli at the two ears constant. In the standard ABI range in which a function was obtained for each unit, the majority of EI neurons (72%) had monotonic (sigmoidal) or near-monotonic IID sensitivity functions. The remainder had nonmonotonic (peaked) IID sensitivity functions, which were attributable either to mixed inhibitory and facilitatory ipsilateral influences or to the fact that the effects of ipsilateral stimulation were superimposed on nonmonotonic effects of changes in intensity at the excitatory ear. 4. IID sensitivity was examined at two or more ABIs (3-5 in most cases) for 40 neurons classified as having monotonic or near-monotonic functions in the standard ABI range and for 7 neurons classified as nonmonotonic. For a small proportion of neurons with monotonic IID sensitivity functions, the form of the function was relatively invariant with changes in ABI. In those monotonic neurons in which the form of the IID sensitivity function varied with changes in ABI, the most common type of variation was that the position of the sloping portion of the function shifted systematically in the direction of larger IIDs favoring the ipsilateral ear as ABI increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Binaural neurons in the mustache bat's inferior colliculus. II. Determinants of spatial responses among 60-kHz EI units.

1. The responses to closed-field and free-field sound stimuli were obtained from EI neurons in the 60-kHz isofrequency representation of the mustache bat's inferior colliculus. The goals of the study were 1) to examine how binaural interactions and the directional properties of the ear shape the spatial response of 60-kHz EI neurons and 2) to examine features of the spatial responses of these isofrequency neurons which may encode the location of a sound. 2. The free-field response of monaural neurons was used to describe directional effects of the head and external ears at 60 kHz. Monaural neurons were most sensitive to sounds originating 26 degrees into the contralateral field, with sharply reduced sensitivity in the ipsilateral field and the lateral extreme of the contralateral field. The interaural intensity difference (IID), computed by assuming that the ears had mirror-image directional sensitivities, was greatest for sounds between 26 and 52 degrees off the vertical midline, where IIDs typically ranged from 20 to 30 dB. These values agree well with previous measures of the directional sensitivity of the ear obtained from cochlear microphonic recordings. 3. The response of a monaural unit to closed-field stimulation was used to predict its response to free-field stimulation. This prediction agreed closely with the observed free-field response, indicating that the monaural unit's free-field response could be explained by the directional sensitivity of the contralateral ear and the unit's response as a function of contralateral sound intensity. 4. EI neurons differed in basic features of their binaural response properties, as described in a companion paper. To examine how these features of binaural inhibition shaped spatial responses, we obtained responses to free-field sounds among neurons whose binaural properties had been thoroughly characterized. We then compared the spatial response to a prediction based upon the directional properties of the ear and the sensitivity of the EI neurons to IIDs and intensity. The close agreement between the observed and predicted spatial responses in 11 of 12 EI units indicated that the spatial responses were determined largely by sensitivity to IIDs and intensity and by the directional properties of the ear. 5. EI neurons in our sample were most sensitive, and responded best, to sounds originating 26-39 degrees into the contralateral field. These spatial response features were independent of the binaural properties of EI neurons. Instead, they depended upon the directional properties of the ears at 60 kHz.(ABSTRACT TRUNCATED AT 400 WORDS)

Binaural neurons in the mustache bat's inferior colliculus. I. Responses of 60-kHz EI units to dichotic sound stimulation.

1. Single-unit responses to closed-field, dichotic sound stimuli were obtained from EI neurons in the mustache bat's inferior colliculus; these neurons are excited by sound to the contralateral ear and inhibited by sound to the ipsilateral ear. All units were tuned to the 60-kHz component of the bat's sonar signal. The goal of the study was to describe basic features of the sensitivity to interaural intensity differences (IIDs) and sound intensity among an isofrequency population of EI neurons. The following paper describes how these features of IID sensitivity shape the response to free-field sounds. 2. Three features of IID sensitivity were considered. The inhibitory threshold (Figs. 1 and 2) described the IID at which inhibitory effects became pronounced; it was defined as the IID at which the excitatory response to contralateral sound was suppressed by 50%. Most units (68%) were inhibited at positive IID values, for which the ipsilateral (inhibitory) sound was more intense. The maximum inhibition (Figs. 1 and 3) described the strength of ipsilateral inhibition; it was defined as the percent that each unit was inhibited below its response to monaural stimulation of the contralateral ear. The majority of units (58%) were almost totally suppressed by a sufficiently intense ipsilateral sound. The IID range (Figs. 1 and 4) described the sharpness or slope of the IID cutoff; it was defined as the IID range over which the response changed from nearly unsuppressed (80% of maximum response) to near maximum suppression (20% of maximum response). Most units (71%) had IID ranges of less than or equal to 15 dB. 3. A significant correlation between the inhibitory threshold and the maximum inhibition (Fig. 5) among the sample of EI units suggests that some common neural mechanisms underlie these features of IID sensitivity. 4. The response of EI neurons to binaural stimuli was a function of sound intensity as well as IID (Fig. 7). In part, this resulted from intensity-dependent changes in properties of binaural inhibition. For most units, basic measures of IID sensitivity changed to a limited extent as the sound intensity changed.(ABSTRACT TRUNCATED AT 400 WORDS)

Binaural response organization within a frequency-band representation of the inferior colliculus: implications for sound localization

The auditory system of the mustache bat (Pteronotus parnellii) contains a disproportionately large representation of a narrow frequency band, corresponding to the dominant, 60 kHz component of its echolocation signal. In the inferior colliculus (IC), the 60 kHz representation comprises an architectonically distinct region called the dorsoposterior division (DPD), which is accessible for detailed physiological study. We examined the topographic distribution of binaural responses within this one frequency-band representation of the inferior colliculus. We describe two primary results. First, neurons with different binaural response properties are spatially segregated into one of four binaural response-specific regions of the DPD: a large region of monaural (EO) responses; two regions containing neurons excited by sound from both ears (EE); and a region containing neurons excited by one ear and inhibited by the other (EI). Regions dominated by 60 kHz EI responses are also found in the lateral extremity of the IC, probably within the external nucleus. These results demonstrate functionally defined subdivisions in a single frequency-band representation of the IC. Moreover, they suggest that brain stem auditory projections to the DPD and/or intrinsic connections within the DPD are highly organized. Second, within the EI region of the DPD, there is a systematic shift in the sensitivity of EI multiunit responses to interaural intensity disparities (IIDs). Dorsally, EI neurons are suppressed only by relatively loud ipsilateral sounds, and there is a systematic decrease in the relative ipsilateral intensity required for suppression at more ventral recording sites. This result demonstrates that neurons sensitive to a sound localization cue are systematically organized within a frequency-band representation of the inferior colliculus. It has implications for the manner in which the location of a sound source is encoded within the primary auditory pathway.

Topographic organization of interaural-intensity-difference sensitivity in deep superior colliculus

The sensitivity to interaural intensity differences (IIDs) of acoustically responsive neurons was examined in multiple microelectrode penetrations along the rostro-caudal axis of deep superior colliculus (SC) in anesthetized cats. The most rostrally located neurons were unresponsive to monaural stimulation but were strongly excited binaurally. IID sensitivity functions for these “predominantly binaural” (PB) neurons were sharply peaked with maximum response at or near zero IID. Caudal to the PB cell area, most neurons were excited by contralateral stimulation and inhibited by ipsilateral stimulation (EI cells). All EI cells were maximally excited over a range of IIDs favoring the contralateral ear and were totally inhibited over a range favoring the ipsilateral ear. The position of the cutoff between excitatory and inhibitory regions was located near zero IID (corresponding to the median plane) for the most rostrally located EI neurons and was shifted progressively to IIDs favoring the contralateral ear (corresponding to increasing contralateral azimuths) for more caudally located EI neurons. The consequence of this topography is that IID, and hence azimuthal location, is represented by the extent of deep SC activated.