[Detection of novel sounds. Multiple manifestations of the same phenomenon?]. / Detección de sonidos nuevos. Existen múltiples manifestaciones de un mismo fenómeno?

INTRODUCTION: Detection of novel sounds must be a basic function of the auditory system, but the underlying neuronal mechanisms are largely unknown. DEVELOPMENT: During repetitive stimulation or a monotonous auditory scene, many auditory neurons show a decrease in their response, presumably due to adaptation. However, these neurons are able to recover and respond again any time there is a change in the stimuli. This process is known as stimulus-specific adaptation (SSA), and could be the basis of the neuronal mechanism for change detection. Neurons showing SSA have been reported both in auditory cortex and subcortical regions, such as the inferior colliculus. Neurons that experience SSA at all levels could be involved in a change detection circuit, but the relationship between neurons in different areas is still unclear. SSA, as found in these neurons, shares a number of characteristics with mismatch negativity (MMN), a component of evoked potentials related to the detection of context novelty, and linked to some processes that involve memory and attention. CONCLUSIONS: The responses to changes in sounds can be observed in multiple ways, ranging from the activity of single neurons to evoked potential recordings. The phenomena observed using these different approaches appear to be manifestations of the same underlying sensory process, which would involve both cortical and subcortical auditory nuclei, and could have its basis in stimulus-specific neuronal adaptation.

Detección de sonidos nuevos. ¿Existen múltiples manifestaciones de un mismo fenómeno? / Detection of novel sounds multiple manifestations of the same phenomenon?

A pesar de que la detección de los sonidos nuevos es una tarea básica del sistema auditivo, todavía sedesconocen en gran medida los procesos neuronales subyacentes. Desarrollo. Durante una estimulación repetitiva o una escena auditiva monótona, muchas neuronas auditivas muestran una reducción de su respuesta, debido a un proceso de adaptación.Este fenómeno, conocido como adaptación específica a los estímulos –stimulus specific adaptation (SSA)–, podría constituir el mecanismo neuronal de la detección de cambios en el entorno acústico. Estudios recientes han descrito la existencia de neuronas que muestran claramente SSA tanto en áreas auditivas corticales como subcorticales (como el colículo inferior) yque podrían formar parte del circuito neuronal de detección de cambios o eventos novedosos. La SSA, como se manifiesta en dichas neuronas, comparte numerosas características con el potencial de disparidad –mismatch negativity (MMN)–, un componentede los potenciales evocados relacionado con la detección de novedad contextual y que puede vincularse a ciertos procesos de memoria y focalización de la atención. A pesar de estos hallazgos, la relación entre SSA y MMN aún no está clara. Conclusiones. Las respuestas neuronales a cambios de sonidos pueden observarse de múltiples formas, desde el registro de neuronas hasta los potenciales evocados. Estas respuestas parecen representar distintas manifestaciones de un mismo procesosensorial subyacente, que involucraría a una serie de áreas auditivas tanto corticales como subcorticales. La base neuronal de este proceso sensorial tendría su origen en alguna forma de adaptación neuronal

Detection of novel sounds must be a basic function of the auditory system, but the underlyingneuronal mechanisms are largely unknown. Development. During repetitive stimulation or a monotonous auditory scene, many auditory neurons show a decrease in their response, presumably due to adaptation. However, these neurons are able to recover and respond again any time there is a change in the stimuli. This process is known as stimulus-specific adaptation (SSA), and could be the basis of the neuronal mechanism for change detection. Neurons showing SSA have been reported bothin auditory cortex and subcortical regions, such as the inferior colliculus. Neurons that experience SSA at all levels could be involved in a change detection circuit, but the relationship between neurons in different areas is still unclear. SSA, as found in these neurons, shares a number of characteristics with mismatch negativity (MMN), a component of evoked potentials relatedto the detection of context novelty, and linked to some processes that involve memory and attention. Conclusions. The responses to changes in sounds can be observed in multiple ways, ranging from the activity of single neurons to evoked potential recordings. The phenomena observed using these different approaches appear to be manifestations of the sameunderlying sensory process, which would involve both cortical and subcortical auditory nuclei, and could have its basis in stimulus-specific neuronal adaptation

Duration selective neurons in the inferior colliculus of the rat: topographic distribution and relation of duration sensitivity to other response properties.

Many animals use duration to help them identify the source and meaning of a sound. Duration-sensitive neurons have been found in the auditory midbrain of mammals and amphibians, where their selectivity seems to correspond to the lengths of species-specific vocalizations. In this study, single neurons in the rat inferior colliculus (IC) were tested for sensitivity to sound duration. About one-half (54%) of the units sampled showed some form of duration selectivity. The majority of these (76%) were long-pass neurons that responded to sounds exceeding some duration threshold (range: 5-60 ms). Band-pass neurons, which only responded to a restricted range of durations, made up 13% of duration-sensitive neurons (best durations: 15-120 ms). Other units displayed short-pass (2%) or mixed (9%) response patterns. The majority of duration-sensitive neurons were localized outside the central nucleus of the IC, especially in the dorsal cortex, where more than one-half of the neurons sampled had long-pass selectivity for duration. Band-pass duration tuned neurons were only found outside the central nucleus. Characteristics of duration-sensitive neurons in the rat support the idea that this filtering arises through an interaction of excitatory and inhibitory inputs that converge in the IC. Band-pass neurons typically responded at sound offset, suggesting that their tuning is created through the same mechanisms that have been described in echolocating bats. The finding that the first-spike latencies of all long-pass neurons were longer than the shortest duration to which they responded supports the idea that they receive transient inhibition before, or simultaneously with, a sustained excitatory input. The ranges of selectivity in rat IC neurons are within the range of durations of rat vocalizations. These data suggest that a population of neurons in the rat IC have evolved to transmit information about behaviorally relevant sound durations using mechanisms that are common to all mammals, with an emphasis on long-pass tuning characteristics.

Relation between intrinsic connections and isofrequency contours in the inferior colliculus of the big brown bat, Eptesicus fuscus.

Information processing in the inferior colliculus depends on interactions between ascending pathways and intrinsic circuitry, both of which exist within a functional tonotopic organization. To determine how local projections of neurons in the inferior colliculus are related to tonotopy, we placed a small iontophoretic injection of biodextran amine at a physiologically characterized location in the inferior colliculus. We then used electrophysiological recording to place a grid of small deposits of Chicago Sky Blue throughout the same frequency range to specify an isofrequency contour. Using three-dimensional computer reconstructions, we analyzed patterns of transport relative to the physiologically determined isofrequency contour to quantify the extent of the intrinsic connection lamina in all three dimensions. We also performed a quantitative analysis of the numbers of cells in different regions relative to the biodextran amine injection. Biodextran amine-labeled fibers were mainly located dorsomedial to the injection site, confined within the isofrequency contour, but biodextran amine-labeled cells were mainly located ventrolateral to the injection site. When we counted numbers of labeled cells classified by morphological type, we found that both elongate and multipolar cells were labeled within the isofrequency contour. Because the dendrites of multipolar cells typically extend outside the isofrequency lamina, it is likely that they receive input from other isofrequency contours and relay it to more dorsomedial portions of their specific isofrequency contour, along with the frequency-specific projections of the elongate cells. Within a given isofrequency contour, there is a consistent organization in which intrinsic connections ascend from the ventrolateral portion to more dorsomedial points along the contour, forming a cascaded system of intrinsic feedforward connections that seem ideally suited to provide the delay lines necessary to produce several forms of selectivity for temporal patterns in inferior colliculus neurons.

Medial superior olive of the big brown bat: neuronal responses to pure tones, amplitude modulations, and pulse trains.

The structure and function of the medial superior olive (MSO) is highly variable among mammals. In species with large heads and low-frequency hearing, MSO is adapted for processing interaural time differences. In some species with small heads and high-frequency hearing, the MSO is greatly reduced in size; in others, including those echolocating bats that have been examined, the MSO is large. Moreover, the MSO of bats appears to have undergone different functional specializations depending on the type of echolocation call used. The echolocation call of the mustached bat contains a prominent CF component, and its MSO is predominantly monaural; the free-tailed bat uses pure frequency-modulated calls, and its MSO is predominantly binaural. To further explore the relation of call structure to MSO properties, we recorded extracellularly from 97 single neurons in the MSO of the big brown bat, Eptesicus fuscus, a species whose echolocation call is intermediate between that of the mustached bat and the free-tailed bat. The best frequencies of MSO neurons in the big brown bat ranged from 11 to 79 kHz, spanning most of the audible range. Half of the neurons were monaural, excited by sound at the contralateral ear, while the other half showed evidence of binaural interactions, supporting the idea that the binaural characteristics of MSO neurons in the big brown bat are midway between those of the mustached bat and the free-tailed bat. Within the population of binaural neurons, the majority were excited by sound at the contralateral ear and inhibited by sound at the ipsilateral ear; only 21% were excited by sound at either ear. Discharge patterns were characterized as transient ON (37%), primary-like (33%), or transient OFF (23%). When presented with sinusoidally amplitude modulated tones, most neurons had low-pass filter characteristics with cutoffs between 100 and 300 Hz modulation frequency. For comparison with the sinusoidally modulated sounds, we presented trains of tone pips in which the pulse duration and interstimulus interval were varied. The results of these experiments indicated that it is not the modulation frequency but rather the interstimulus interval that determines the low-pass filter characteristics of MSO neurons.

Neural measurement of sound duration: control by excitatory-inhibitory interactions in the inferior colliculus.

In the inferior colliculus (IC) of the big brown bat, a subpopulation of cells ( approximately 35%) are tuned to a narrow range of sound durations. Band-pass tuning for sound duration has not been seen at lower levels of the auditory pathway. Previous work suggests that it arises at the IC through the interaction of sound-evoked, temporally offset, excitatory and inhibitory inputs. To test this hypothesis, we recorded from duration-tuned neurons in the IC and examined duration tuning before and after iontophoretic infusion of antagonists to gamma-aminobutyric acid-A (GABA(A)) (bicuculline) or glycine (strychnine). The criterion for duration tuning was that the neuron's spike count as a function of duration had a peak value at one duration or a range of durations that was >/=2 times the lowest nonzero value at longer durations. Out of 21 units tested with bicuculline, duration tuning was eliminated in 15, broadened in two, and unaltered in four. Out of 10 units tested with strychnine, duration tuning was eliminated in four, broadened in one, and unaltered in five. For units tested with both bicuculline and strychnine, bicuculline had a greater effect on reducing or abolishing duration tuning than did strychnine. Bicuculline and strychnine both produced changes in discharge pattern. There was nearly always a shift from an offset response to an onset response, indicating that in the predrug condition, inhibition arrived simultaneously with excitation or preceded it. There was often an increase in the length of the spike train, indicating that in the predrug condition, inhibition also coincided with later parts of excitation. These findings support two hypotheses. First, duration tuning is created in the IC. Second, although the construction of duration tuning varies in some details among IC neurons, it follows three rules: 1) an excitatory and an inhibitory event are temporally linked to the onset of sound but temporally offset from one another; 2) the duration of some inhibitory event must be linked to the duration of the sound; 3) an excitatory event must be linked to the offset of sound.

Neural population coding and auditory temporal pattern analysis.

Over the 2 decades that have elapsed since Robert Erickson first published his pioneering work on across-fiber patterns in the gustatory system, the idea that information is represented by a population code has become almost universally accepted among neuroscientists. Although the concept of a population code is an implicit theoretical assumption underlying most of the work done in neuroscience today, the details of how population codes operate in specific systems remain unclear in many respects. This article reviews electrophysiological studies of the auditory system of echolocating bats that show that information about sound is initially represented across both space and time by relative amounts of activity in populations of excitatory and inhibitory neurons with different discharge patterns, different sensitivity functions, and different latencies. At the next level, each neuron in the auditory midbrain receives convergent input from a specific population of these lower brainstem neurons and acts as a "readout" of activity within this population. As a result, midbrain neurons become selectively tuned to stimulus features, for example, signal duration, to which neurons at lower levels respond indiscriminately. Intracellular recordings from auditory midbrain neurons show some of the mechanisms by which population input is processed. The known projection patterns of the midbrain "readout" neurons indicate that they, in turn, must become part of a new spatio-temporal population code that is transmitted to neurons at the thalamus, where additional forms of selectivity and patterns of output arise.

Timing in the auditory system of the bat.

Echolocating bats use audition to guide much of their behavior. As in all vertebrates, their lower brainstem contains a number of parallel auditory pathways that provide excitatory or inhibitory outputs differing in their temporal discharge patterns and latencies. These pathways converge in the auditory midbrain, where many neurons are tuned to biologically important parameters of sound, including signal duration, frequency-modulated sweep direction, and the rate of periodic frequency or amplitude modulations. This tuning to biologically relevant temporal patterns of sound is created through the interplay of the time-delayed excitatory and inhibitory inputs to midbrain neurons. Because the tuning process requires integration over a relatively long time period, the rate at which midbrain auditory neurons respond corresponds to the cadence of sounds rather than their fine structure and may provide an output that is closely matched to the rate at which motor systems operate.

Arctiid moths and bat echolocation: broad-band clicks interfere with neural responses to auditory stimuli in the nuclei of the lateral lemniscus of the big brown bat.

Clicks emitted by arctiid moths interfere with the ranging ability of echolocating bats. To identify possible neural correlates of this interference, we recorded responses of single units in the nuclei of the lateral lemniscus to combinations of a broad-band click and a test signal (pure tones or frequency-modulated sweeps). In 77% of 87 units tested, clicks interfered with neural responses to the test stimuli. The interference fell into two categories: latency ambiguity and suppression. Units showing latency ambiguity responded to both the click and the test signal. However, when the click occurred within a window of approximately 3 ms before the onset of the test signal, the latency of the response to the test signal was affected. Units that were suppressed did not respond to clicks. Nevertheless, when a click was presented immediately before or simultaneously with a test signal, the response to the test signal was eliminated. Both types of units were found throughout the lateral lemniscus except for the columnar division of the ventral nucleus, where all units tested exhibited latency ambiguity. There is a close match between the single unit data and previous studies of range difference discrimination in the presence of clicks.

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 I 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.

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

Changes in amplitude are a characteristic feature of most natural sounds, including the biosonar signals used by bats for echolocation. Previous evidence suggests that the nuclei of the lateral lemniscus play an important role in processing timing information that is essential for target range determination in echolocation. Neurons that respond to unmodulated tones with a sustained discharge are found in the dorsal nucleus (DNLL), intermediate nucleus (INLL) and multipolar cell division of the ventral nucleus (VNLLm). These neurons provide a graded response over a broad dynamic range of intensities, and would be expected to provide information about the amplitude envelope of a modulated signal. Neurons that respond only at the onset of a tone make up a small proportion of cells in DNLL, INLL and VNLLm, but are the only type found in the columnar division of the ventral nucleus (VNLLc). Onset neurons in VNLLc maintain a constant latency across a wide range of stimulus frequencies and intensities, thus providing a precise marker for when a sound begins. To determine how these different functional classes of cells respond to amplitude changes, we presented sinusoidally amplitude modulated (SAM) signals monaurally to awake, restrained bats and recorded the responses of single neurons extracellularly. There were clear differences in the ability of neurons in the different cell groups to respond to SAM. In the VNLLm, INLL and DNLL, 90% of neurons responded to SAM with a synchronous discharge. Neurons in the VNLLc responded poorly or not at all to SAM signals. This finding was unexpected given the precise onset responses of VNLLc neurons to unmodulated tones and their ability to respond synchronously to sinusoidally frequency modulated (SFM) signals. Among neurons that responded synchronously to SAM, synchronization as a function of modulation rate described either a bandpass or a lowpass function, with the majority of bandpass functions in neurons that responded to unmodulated tones with a sustained discharge. The maximal modulation rates that elicited synchronous responses were similar for the different cell groups, ranging from 320 Hz in VNLLm to 230 Hz in DNLL. The range of best modulation rates was greater for SAM than for SFM; this was also true of the range of maximal modulation rates at which synchronous discharge occurred. There was little correlation between a neuron's best modulation rate or maximal modulation rate for SAM signals and those for SFM signals, suggesting that responsiveness to amplitude and frequency modulations depends on different neural processing mechanisms.

The columnar region of the ventral nucleus of the lateral lemniscus in the big brown bat (Eptesicus fuscus): synaptic arrangements and structural correlates of feedforward inhibitory function.

Neurons of the columnar region of the ventral nucleus of the lateral lemniscus of Eptesicus fuscus respond with high-precision constant-latency responses to sound onsets and possess remarkably broad tuning. To study the synaptic basis for this specialized monaural auditory processing and to elucidate the excitatory or inhibitory nature of the input and output circuitry, we have used classical transmission electron microscopy, and postembedding immunocytochemistry for gamma aminobutyric acid (GABA) and glycine on serial semithin sections. The dominant putatively excitatory perisomatic input is provided by large calyx-like terminals that possess round synaptic vesicles and asymmetric synaptic contacts. Additionally, calyces contact the dendrites of neighboring neurons. Putatively inhibitory small boutons possess pleomorphic or flattened synaptic vesicles and symmetrical contacts and are sparsely distributed on somata and dendrites. Almost all neurons are glycine-immunoreactive. There is a moderate amount of glycine-immunoreactive puncta; GABA-immunoreactive puncta are rare. This suggests that (1) there is a fast robust excitatory synaptic input via calyx-like perisomatic endings, (2) calyx-like endings distribute frequency-specific excitatory input across isofrequency sheets by virtue of parallel synapses to somata and adjacent dendrites, and thus, dendritic integration may contribute to the broadening of frequency tuning, (3) the columnar region forms an inhibitory glycinergic feedforward relay in the ascending auditory pathway, a relay that is probably involved in creating filters for time-varying signals.

Neural tuning to sound duration in the inferior colliculus of the big brown bat, Eptesicus fuscus.

Neural tuning to different sound durations may be a useful filter for identification of certain sounds, especially those that are biologically important. The auditory midbrains of mammals and amphibians contain neurons that appear to be tuned to sound duration. In amphibians, neurons are tuned to durations of sound that are biologically important. The purpose of this study was to characterize responses of neurons in the inferior colliculus (IC) of the big brown bat, Eptesicus fuscus, to sounds of different durations. Our aims were to determine what percent of neurons are duration tuned and how best durations are correlated to durations of echolocation calls, and to examine response properties that may be relevant to the mechanism for duration tuning, such as latency and temporal firing pattern; we also examined frequency tuning and rate-level functions. We recorded from 136 single units in the central nucleus of the IC of unanesthetized bats. The stimuli were pure tones, frequency-modulated sweeps, and broadband noise. The criterion for duration tuning was an increase in spike count of > or = 50% at some durations compared with others. Of the total units sampled, 36% were tuned to stimulus duration. All of these units were located in the caudal half of the IC. Best duration for most units ranged from < 1 to 10 ms, but a few had best durations up to > or = 20 ms. This range is similar to the range of durations of echolocation calls used by Eptesicus. All duration-tuned neurons responded transiently. The minimum latency was always longer than the best duration. Duration-tuned units have best durations and best frequencies that match the temporal structure and frequency range of the echolocation calls. Thus the results raise the hypothesis that neurons in the IC of Eptesicus, and probably the auditory midbrain of other vertebrates, are tuned to biologically important sound durations. We suggest a model for duration tuning consisting of three components: 1) inhibitory input that is correlated with the onset of the stimulus and is sustained for the stimulus duration; 2) transient excitation that is correlated with the offset of the stimulus; and 3) transient excitation that is correlated with the onset of the stimulus but is delayed in time relative to the onset of inhibition. For the neuron to fire, the two excitatory events must coincide in time; noncoincident excitatory events are not sufficient.

Neural selectivity and tuning for sinusoidal frequency modulations in the inferior colliculus of the big brown bat, Eptesicus fuscus.

Most communication sounds and most echolocation sounds, including those used by the big brown bat (Eptesicus fuscus), contain frequency-modulated (FM) components, including cyclical FM. Because previous studies have shown that some neurons in the inferior colliculus (IC) of this bat respond to linear FM sweeps but not to pure tones or noise, we asked whether these or other neurons are specialized for conveying information about cyclical FM signals. In unanesthetized bats, we tested the response of 116 neurons in the IC to pure tones, noise with various bandwidths, single linear FM sweeps, sinusoidally amplitude-modulated signals, and sinusoidally frequency-modulated (SFM) signals. With the use of these stimuli, 20 neurons (17%) responded only to SFM, and 10 (9%) responded best to SFM but also responded to one other test stimulus. We refer to the total 26% of neurons that responded best to SFM as SFM-selective neurons. Fifty-nine neurons (51%) responded about equally well to SFM and other stimuli, and 27 (23%) did not respond to SFM but did respond to other stimuli. Most SFM-selective neurons responded to a limited range of modulation rates and a limited range of modulation depths. The range of modulation rates over which individual neurons responded was 5-170 Hz (n = 20). Thus SFM-selective neurons respond to low modulation rates. The depths of modulations to which the neurons responded ranged from +/-0.4 to +/-19 kHz (n = 15). Half of the SFM-selective neurons did not respond to the first cycle of SFM. This finding suggests that the mechanism for selective response to SFM involves neural delays and coincidence detectors in which the response to one part of the SFM cycle coincides in time either with the response to a later part of the SFM cycle or with the response to the first part of the next cycle. The SFM-selective neurons in the IC responded to a lower and more limited range of SFM rates than do neurons in the nuclei of the lateral lemniscus of this bat. Because the FM components of biological sounds usually have low rates of modulation, we suggest that the tuning of these neurons is related to biologically important sound parameters. The tuning could be used to detect FM in echolocation signals, modulations in high-frequency sounds that are generated by wing beats of some beetles, or social communication sounds of Eptesicus.

Whole-cell patch-clamp recording reveals subthreshold sound-evoked postsynaptic currents in the inferior colliculus of awake bats.

The inferior colliculus receives excitatory and inhibitory input from parallel auditory pathways that differ in discharge patterns, latencies, and binaural properties. Processing in the inferior colliculus may depend on the temporal sequence in which excitatory and inhibitory synaptic inputs are activated and on the resulting balance between excitation and inhibition. To explore this issue at the cellular level, we used the novel approach of whole-cell patch-clamp recording in the midbrain of awake bats (Eptesicus fuscus) to record EPSCs or IPSCs. Sound-evoked EPSCs were recorded in most neurons. These EPSCs were frequently preceded by an IPSC, followed by an IPSC, or both. These findings help explain the large latency range and transient responses that characterize inferior colliculus neurons. The EPSC was sometimes followed by long-lasting oscillatory currents, suggesting that a single brief sound sets up a pattern of altered excitability that persists far beyond the duration of the initial sound. In three binaural neurons, ipsilateral sound evoked a large IPSC that partially or totally canceled the EPSC evoked by contralateral sound. In one binaural neuron with ipsilaterally evoked IPSCs, contralaterally evoked IPSCs occurred in response to frequencies above and below the neuron's best frequency. Thus, both monaural and binaural interactions can occur at single inferior colliculus neurons. These results show that whole-cell patch-clamp recording offers a powerful means of understanding how subthreshold processes determine the responses of auditory neurons.

Distribution of GABAA, GABAB, and glycine receptors in the central auditory system of the big brown bat, Eptesicus fuscus.

Quantitative autoradiographic techniques were used to compare the distribution of GABAA, GABAB, and glycine receptors in the subcortical auditory pathway of the big brown bat, Eptesicus fuscus. For GABAA receptors, the ligand used was 35S-t-butylbicyclophosphorothionate (TBPS) for GABAB receptors, 3H-GABA was used as a ligand in the presence of isoguvacine to block binding to GABAA sites; for glycine, the ligand used was 3H-strychnine. In the subcortical auditory nuclei there appears to be at least a partial complementarity in the distribution of GABAA receptors labeled with 35S-TBPS and glycine receptors labeled with 3H-strychnine, GABAA receptors were concentrated mainly in the inferior colliculus (IC) and medial geniculate nucleus, whereas glycine receptors were concentrated mainly in nuclei below the level of the IC. Within the IC, there was a graded spatial distribution of 35S-TBPS binding; the most dense labeling was in the dorsomedial region, but very sparse labeling was observed in the ventrolateral region. There was also a graded spatial distribution of 3H-strychnine binding. The most dense labeling was in the ventral and lateral regions and the weakest labeling was in the dorsomedial region. Thus, in the IC, the distribution of 35S-TBPS was complementary to that of 3H-strychnine. GABAB receptors were distributed at a low level throughout the subcortical auditory nuclei, but were most prominent in the dorsomedial part of the IC.

A neuroethological theory of the operation of the inferior colliculus.

A general statement of the function of the inferior colliculus is lacking, even after more than three decades of electrophysiological investigation. A neuroethological theory is proposed that accounts for a large and diverse body of evidence. Although aimed at characterizing the inferior colliculus in mammals, the theory also applies generally to the auditory midbrain in vertebrates. The theory has two hypotheses: (1) Tuning processes in the inferior colliculus are related to the biological importance of sounds. (2) There is a change in timing properties at the inferior colliculus, from rapid input to slowed output; this transformation is related to the timing of specific behaviors. Expressed in neuroethological terms, at least some neurons in the inferior colliculus are tuned to sign-stimuli, and the processing of these sign stimuli triggers fixed action patterns for hunting, escape or vocal communication. The resulting temporal transformation adjusts the pace of sensory input to the pace of behavior. Evidence for the theory comes from anatomical, neurophysiological and behavioral studies and includes: (1) massive convergence of parallel auditory pathways at the inferior colliculus, (2) interaction of the inferior colliculus with motor systems, (3) tuning of auditory midbrain neurons to biologically important sounds, (4) the slow pace of neural processing at the inferior colliculus, (5) the slow pace of motor output. The theory has the following implications. Neurons in the inferior colliculus are filters for sounds that require immediate action, such as certain sounds made by prey, predators or conspecifics. Neural processing in the inferior colliculus is species specific, resulting in filtering for these kinds of sounds. Specific action patterns should be correlated with the activity of neurons in the inferior colliculus. Motor activities may modify neural processing in inferior colliculus neurons. The rate at which information is transmitted to the thalamus is regulated by the inferior colliculus.

Spatial tuning of neurons in the inferior colliculus of the big brown bat: effects of sound level, stimulus type and multiple sound sources.

We examined factors that affect spatial receptive fields of single units in the central nucleus of the inferior colliculus of Eptesicus fuscus. Pure tones, frequency- or amplitude-modulated sounds, or noise bursts were presented in the free-field, and responses were recorded extracellularly. For 58 neurons that were tested over a 30 dB range of sound levels, 7 (12%) exhibited a change of less than 10 degrees in the center point and medical border of their receptive field. For 28 neurons that were tested with more than one stimulus type, 5 (18%) exhibited a change of less than 10 degrees in the center point and medial border of their receptive field. The azimuthal response ranges of 19 neurons were measured in the presence of a continuous broadband noise presented from a second loudspeaker set at different fixed azimuthal positions. For 3 neurons driven by a contralateral stimulus only, the effect of the noise was simple masking. For 11 neurons driven by sound at either side, 8 were unaffected by the noise and 1 showed a simple masking effect. For the remaining 2, as well as for 5 neurons that were excited by contralateral sound and inhibited by ipsilateral sound, the peak of the azimuthal response range shifted toward the direction of the noise.

Origin of ascending projections to the nuclei of the lateral lemniscus in the big brown bat, Eptesicus fuscus.

The nuclei of the lateral lemniscus in the echolocating bat, Eptesicus fuscus, are large and highly differentiated. In each nucleus, different characteristic response properties predominate. To determine whether the dissimilar response properties are due in part to differential ascending input, we examined the retrograde transport from small deposits of horseradish peroxidase (HRP) or HRP conjugated with wheat germ agglutinin (WGA-HRP) in the nuclei of the lateral lemniscus. The intermediate nucleus (INLL) and the two divisions of the ventral nucleus (VNLL) receive almost exclusively monaural input from the anteroventral and posteroventral cochlear nuclei and from the medial nucleus of the trapezoid body. Lesser inputs originate in the lateral nucleus of the trapezoid body and the ventral periolivary area. Although the three monaural nuclei of the lateral lemniscus all receive input from the same set of nuclei, and from the same identified cell types in the cochlear nucleus, there is a difference in the relative proportions of input from these sources. The dorsal nucleus (DNLL) receives input mostly from binaural structures, the lateral and medial superior olives and the contralateral DNLL, with only a minor projection from the cochlear nucleus. The lateral and medial superior olives project bilaterally; the bilateral projection from the medial superior olive is unusual in that it is found in only a few mammalian species. The results show a segregated pattern of binaural projections to DNLL and monaural projections to INLL and VNLL that is consistent with the binaural response properties found in DNLL and the exclusively monaural response properties found in INLL and VNLL. The differences in response properties between monaural nuclei, however, are not due to input from different nuclei or cell types but may be influenced by differing magnitudes of the constituent ascending projections.