A novel concept for dynamic adjustment of auditory space.

Traditionally, the auditory system is thought to serve reliable sound localization. Stimulus-history driven feedback circuits in the early binaural pathway, however, contradict this canonical concept and raise questions about their functional significance. Here we show that stimulus-history dependent changes in absolute space perception are poorly captured by the traditional labeled-line and hemispheric-difference models of auditory space coding. We therefore developed a new decoding model incorporating recent electrophysiological findings in which sound location is initially computed in both brain hemispheres independently and combined to yield a hemispherically balanced code. This model closely captures the observed absolute localization errors caused by stimulus history, and furthermore predicts a selective dilation and compression of perceptional space. These model predictions are confirmed by improvement and degradation of spatial resolution in human listeners. Thus, dynamic perception of auditory space facilitates focal sound source segregation at the expense of absolute sound localization, questioning existing concepts of spatial hearing.

Late postnatal development of intrinsic and synaptic properties promotes fast and precise signaling in the dorsal nucleus of the lateral lemniscus.

The dorsal nucleus of the lateral lemniscus (DNLL) is an auditory brain stem structure that generates a long-lasting GABAergic output, which is important for binaural processing. Despite its importance in binaural processing, little is known about the cellular physiology and the synaptic input kinetics of DNLL neurons. To assess the relevant physiological parameters of DNLL neurons, their late postnatal developmental profile was analyzed in acute brain slices of 9- to 26-day-old Mongolian gerbils. The observed developmental changes in passive membrane and action potential (AP) properties all point toward an improvement of fast and precise signal integration in these neurons. Accordingly, synaptic glutamatergic and GABAergic current kinetics accelerate with age. The changes in intrinsic and synaptic properties contribute nearly equally to reduce the latency and jitter in AP generation and thus enhance the temporal precision of DNLL neurons. Furthermore, the size of the synaptic NMDA current is developmentally downregulated. Despite this developmental reduction, DNLL neurons display an NMDA-dependent postsynaptic amplification of AP generation, known to support high firing rates, throughout this developmental period. Taken together, our findings indicate that during late postnatal development DNLL neurons are optimized for high firing rates with high temporal precision.

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.

Structure and function of the bat superior olivary complex.

The superior olivary complex (SOC) is a mammalian auditory brainstem structure that contains several nuclei. Some of them are part of the ascending system projecting to higher auditory centers, others belong to the descending system projecting to the cochlear nuclei or the cochlea itself. The main nuclei of the ascending system, the lateral and medial superior olive (LSO, MSO), as well as the lateral and medial nuclei of the trapezoid body (LNTB, MNTB), have been traditionally associated with sound localization. Here we review the results of recent studies on the main SOC nuclei in echolocating bats. These studies suggest that some SOC structures and functions are highly conserved across mammals (e.g., the LSO, which is associated with interaural intensity difference processing), while others are phylogenetically highly variable in both form and function (e.g., the MSO, traditionally associated with interaural time difference processing). For the MSO, these variations indicate that we should broaden our view regarding what functions the MSO might participate in, since its function in echolocation seems to lie in the context of pattern recognition rather than sound localization. Furthermore, across bat species, variations in the form and physiology of the MSO can be linked to specific behavioral adaptations associated with different echolocation strategies. Finally, the comparative approach, including auditory specialists such as bats, helps us to reach a more comprehensive view of the functional anatomy of auditory structures that are still poorly understood, like the nucleus of the central acoustic tract (NCAT).

Duration tuning in the mouse auditory midbrain.

Temporal cues, including sound duration, are important for sound identification. Neurons tuned to the duration of pure tones were first discovered in the auditory system of frogs and bats and were discussed as specific adaptations in these animals. More recently duration sensitivity has also been described in the chinchilla midbrain and the cat auditory cortex, indicating that it might be a more general phenomenon than previously thought. However, it is unclear whether duration tuning in mammals is robust in face of changes of stimulus parameters other than duration. Using extracellular single-cell recordings in the mouse inferior colliculus, we found 55% of cells to be sensitive to stimulus duration showing long-pass, short-pass, or band-pass filter characteristics. For most neurons, a change in some other stimulus parameter, (e.g., intensity, frequency, binaural conditions, or using noise instead of pure tones) altered and sometimes abolished duration-tuning characteristics. Thus in many neurons duration tuning is interdependent with other stimulus parameters and, hence, might be context dependent. A small number of inferior colliculus neurons, in particular band-pass neurons, exhibited stable filter characteristics and could therefore be referred to as "duration selective." These findings support the idea that duration tuning is a general phenomenon in the mammalian auditory system.

Temporal processing in sensory systems.

The idea that sensory information is represented by the temporal firing patterns of neurons or entire networks, rather than by firing rates measured over long integration times, has recently gained increasing experimental support. A number of mechanisms that help to preserve temporal information in ascending sensory systems have been identified, and the role of inhibition in these processes has been characterized. Furthermore, it has become obvious that temporal processing and the representation of sensory events by temporal spike patterns are highly dependent upon the behavioral state of the animal or experimental subject.

Latency as a function of intensity in auditory neurons: influences of central processing.

The response latencies of sensory neurons typically shorten with increases in stimulus intensity. In the central auditory system this phenomenon should have a significant impact on a number of auditory functions that depend critically on an integration of precisely timed neural inputs. Evidence from previous studies suggests that the auditory system not only copes with the potential problems associated with intensity-dependent latency change, but that it also modifies latency change to shape the response properties of many cells for specific functions. This observation suggests that intensity-dependent latency change may undergo functional transformations along the auditory neuraxis. The goal of our study was to explore these transformations by making a direct, quantitative comparison of intensity-dependent latency change among a number of auditory centers from the lower brainstem to the thalamus. We found two main ways in which intensity-dependent latency change transformed along the neuraxis: (1) the range of latency change increased substantially and (2) one particular type of latency change, which has been suggested to be associated with sensitivity to temporally segregated stimulus components, occurred only at the highest centers tested, the midbrain and thalamus. Additional testing in the midbrain (inferior colliculus) indicated that inhibitory inputs are involved in shaping latency change. Our findings demonstrate that the central auditory system modifies intensity-dependent latency changes. We suggest that these changes may be functionally incorporated, actively enhanced, or modified to suit specific functions of the auditory system.

The function of the medial superior olive in small mammals: temporal receptive fields in auditory analysis.

Traditionally, the medial superior olive, a mammalian auditory brainstem structure, is considered to encode interaural time differences, the main cue for localizing low-frequency sounds. Detection of binaural excitatory and inhibitory inputs are considered as an underlying mechanism. Most small mammals, however, hear high frequencies well beyond 50 kHz and have small interaural distances. Therefore, they can not use interaural time differences for sound localization and yet possess a medial superior olive. Physiological studies in bats revealed that medial superior olive cells show similar interaural time difference coding as in larger mammals tuned to low-frequency hearing. Their interaural time difference sensitivity, however, is far too coarse to serve in sound localization. Thus, interaural time difference sensitivity in medial superior olive of small mammals is an epiphenomenon. We propose that the original function of the medial superior olive is a binaural cooperation causing facilitation due to binaural excitation. Lagging inhibitory inputs, however, suppress reverberations and echoes from the acoustic background. Thereby, generation of antagonistically organized temporal fields is the basic and original function of the mammalian medial superior olive. Only later in evolution with the advent of larger mammals did interaural distances, and hence interaural time differences, became large enough to be used as cues for sound localization of low-frequency stimuli.

The evolution of temporal processing in the medial superior olive, an auditory brainstem structure.

A basic concept in neuroscience is to correlate specific functions with specific neuronal structures. By discussing a specific example, an alternative concept is proposed: structures may be linked to rules of processing and these rules may serve different functions in different species or at different stages of evolution. The medial superior olive (MSO), a mammalian auditory brainstem structure, has been thought to solely process interaural time differences (ITD), the main cue for localizing low frequency sounds. Recent findings, however, indicate that this is not its only function since mammals that do not hear low frequencies and do not use ITDs for sound localization also possess a MSO. Recordings from the bat MSO indicate that it processes temporal cues in the milli- and submillisecond range, based on monaural or binaural inputs. In bats, and most likely in other small mammals, this temporal processing is related to pattern recognition and echo suppression rather than sound localization. However, the underlying mechanism, coincidence detection of several inputs, creates an epiphenomenal ITD sensitivity that is of no use for small mammals like bats or ancestral mammals. Such an epiphenomenal ITD sensitivity would have been a pre-adaptation which, when mammals grew larger during evolution and when localization of low frequency sounds became a question of survival, suddenly gained relevance. This way the MSO became involved in a new function without changing its basic rules of processing.

Interdependence of spatial and temporal coding in the auditory midbrain.

To date, most physiological studies that investigated binaural auditory processing have addressed the topic rather exclusively in the context of sound localization. However, there is strong psychophysical evidence that binaural processing serves more than only sound localization. This raises the question of how binaural processing of spatial cues interacts with cues important for feature detection. The temporal structure of a sound is one such feature important for sound recognition. As a first approach, we investigated the influence of binaural cues on temporal processing in the mammalian auditory system. Here, we present evidence that binaural cues, namely interaural intensity differences (IIDs), have profound effects on filter properties for stimulus periodicity of auditory midbrain neurons in the echolocating big brown bat, Eptesicus fuscus. Our data indicate that these effects are partially due to changes in strength and timing of binaural inhibitory inputs. We measured filter characteristics for the periodicity (modulation frequency) of sinusoidally frequency modulated sounds (SFM) under different binaural conditions. As criteria, we used 50% filter cutoff frequencies of modulation transfer functions based on discharge rate as well as synchronicity of discharge to the sound envelope. The binaural conditions were contralateral stimulation only, equal stimulation at both ears (IID = 0 dB), and more intense at the ipsilateral ear (IID = -20, -30 dB). In 32% of neurons, the range of modulation frequencies the neurons responded to changed considerably comparing monaural and binaural (IID =0) stimulation. Moreover, in approximately 50% of neurons the range of modulation frequencies was narrower when the ipsilateral ear was favored (IID = -20) compared with equal stimulation at both ears (IID = 0). In approximately 10% of the neurons synchronization differed when comparing different binaural cues. Blockade of the GABAergic or glycinergic inputs to the cells recorded from revealed that inhibitory inputs were at least partially responsible for the observed changes in SFM filtering. In 25% of the neurons, drug application abolished those changes. Experiments using electronically introduced interaural time differences showed that the strength of ipsilaterally evoked inhibition increased with increasing modulation frequencies in one third of the cells tested. Thus glycinergic and GABAergic inhibition is at least one source responsible for the observed interdependence of temporal structure of a sound and spatial cues.

Sensitivity to interaural time differences in the medial superior olive of a small mammal, the Mexican free-tailed bat.

Neurons in the medial superior olive (MSO) are thought to encode interaural time differences (ITDs), the main binaural cues used for localizing low-frequency sounds in the horizontal plane. The underlying mechanism is supposed to rely on a coincidence of excitatory inputs from the two ears that are phase-locked to either the stimulus frequency or the stimulus envelope. Extracellular recordings from MSO neurons in several mammals conform with this theory. However, there are two aspects that remain puzzling. The first concerns the role of the MSO in small mammals that have relatively poor low-frequency hearing and whose heads generate only very small ITDs. The second puzzling aspect of the scenario concerns the role of the prominent binaural inhibitory inputs to MSO neurons. We examined these two unresolved issues by recording from MSO cells in the Mexican free-tailed bat. Using sinusoidally amplitude-modulated tones, we found that the ITD sensitivities of many MSO cells in the bat were remarkably similar to those reported for larger mammals. Our data also indicate an important role for inhibition in sharpening ITD sensitivity and increasing the dynamic range of ITD functions. A simple model of ITD coding based on the timing of multiple inputs is proposed. Additionally, our data suggest that ITD coding is a by-product of a neuronal circuit that processes the temporal structure of sounds. Because of the free-tailed bat's small head size, ITD coding is most likely not the major function of the MSO in this small mammal and probably other small mammals.

GABAergic and glycinergic inhibition sharpens tuning for frequency modulations in the inferior colliculus of the big brown bat.

Discrimination of amplitude and frequency modulated sounds is an important task of auditory processing. Experiments have shown that tuning of neurons to sinusoidally frequency- and amplitude-modulated (SFM and SAM, respectively) sounds becomes successively narrower going from lower to higher auditory brain stem nuclei. In the inferior colliculus (IC), many neurons are sharply tuned to the modulation frequency of SFM sounds. The purpose of this study was to determine whether GABAergic or glycinergic inhibition is involved in shaping the tuning for the modulation frequency of SFM sounds in IC neurons of the big brown bat (Eptesicus fuscus). We recorded the response of 56 single units in the central nucleus of the IC to SFM stimuli before and during the application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline or the glycine receptor antagonist strychnine. To evaluate tuning to the modulation frequency, the normalized spike count (normalized according to the maximal response for each condition tested) was plotted versus the modulation frequency and the upper and lower 50% cutoff points were determined. Bicuculline increased the upper cutoff in 46% of the neurons by >/=25%. The lower cutoff decreased in 48% of the neurons tested. In some neurons (approximately 30%), a sharpening of the tuning by bicuculline was observed. Strychnine induced an increase of the upper cutoff in almost half of the neurons. Compared with bicuculline these changes were smaller. The lower cutoff decreased in 50% of the neurons with strychnine. The synchronization coefficient (SC) was calculated and compared for three modulation frequencies (50, 100, and 200 Hz) between predrug and drug condition. For all neurons, synchronization decreased (n = 36) or did not change (n = 26) during drug application. This was mainly an effect of the prolonged discharge in response to each cycle. Under predrug conditions, many neurons exhibited selectivity to the direction of the FM, hence they only responded once to each cycle. In a minority of neurons, direction selectivity was abolished by drug application. The main finding was that neuronal inhibition sharpens tuning to the modulation frequency in the majority of neurons. In general, changes induced by bicuculline or strychnine were comparable.

Medial superior olive in the free-tailed bat: response to pure tones and amplitude-modulated tones.

In mammals with good low-frequency hearing and a moderate to large interear distance, neurons in the medial superior olive (MSO) are sensitive to interaural time differences (ITDs). Most small mammals, however, do not hear low frequencies and do not experience significant ITDs, suggesting that their MSOs participate in functions other than ITD coding. In one bat species, the mustached bat, the MSO is a functionally monaural nucleus, acting as a low-pass filter for the rate of sinusoidally amplitude-modulated (SAM) stimuli. We investigated whether the more typical binaural MSO of the MExican free-tailed bat also acts as an SAM filter. We recorded from 60 MSO neurons with their best frequencies covering the entire audiogram of this bat. The majority revealed bilateral excitation and indirect evidence for inhibition (EI/EI; 55%). The remaining neurons exhibited reduced inputs, mostly lacking ipsilateral inputs (28% I/EI; 12% O/EI; 5% EI/O). Most neurons (64%) responded with a phasic discharge to pure tones; the remaining neurons exhibited an additional sustained component. For stimulation with pure tones, two thirds of the cells exhibited monotonic rate-level functions for ipsilateral, contralateral, or binaural stimulation. In contrast, nearly all neurons exhibited nonmonotonic rate-level functions when tested with SAM stimuli. Eighty-eight percent of the neurons responded with a phase-locked discharge to SAM stimuli at low modulation rates and exhibited low-pass filter characteristics in the modulation transfer function (MTF) for ipsilateral, contralateral, and binaural stimulation. The MTF for ipsilateral stimulation usually did not match that for contralateral stimulation. Introducing interaural intensity differences (IIDs) changed the MTF in unpredictable ways. We also found that responses to SAMs depended on the carrier frequency. In some neurons we measured the time course of the ipsilaterally and contralaterally evoked inhibition by presenting brief frequency-modulated sweeps at different ITDs. The duration and timing of inhibition could be related to the SAM cutoff for binaural stimulation. We conclude that the response of the MSO in the free-tailed bat is created by a complex interaction of inhibition and excitation. The different time constants of inputs create a low-pass filter for SAM stimuli. However, the MSO output is an integrated response to the temporal structure of a stimulus as well as its azimuthal position, i.e., IIDs. There are no in vivo results concerning filter characteristics in a "classical" MSO, but our data confirm an earlier speculation about this interdependence based on data accessed from a gerbil brain slice preparation.

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.

Neural delays shape selectivity to interaural intensity differences in the lateral superior olive.

Neurons in the lateral superior olive (LSO) respond selectively to interaural intensity differences (IIDs), one of the chief cues used to localize sounds in space. LSO cells are innervated in a characteristic pattern: they receive an excitatory input from the ipsilateral ear and an inhibitory input from the contralateral ear. Consistent with this pattern, LSO cells generally are excited by sounds that are more intense at the ipsilateral ear and inhibited by sounds that are more intense at the contralateral ear. Despite their relatively homogeneous pattern of innervation, IID selectivity varies substantially from cell to cell, such that selectivities are distributed over the range of IIDs that would be encountered in nature. For some time, researchers have speculated that the relative timing of the excitatory and inhibitory inputs to an LSO cell might shape IID selectivity. To test this hypothesis, we recorded from 50 LSO cells in the free-tailed bat while presenting stimuli that varied in interaural intensity and in interaural time of arrival. The results suggest that, for more than half of the cells, the latency of inhibition was several hundred microseconds longer than the latency of excitation. Increasing the intensity to the inhibitory ear shortened the latency of inhibition and brought the timing of the inputs from the two ears into register. Thus, a neural delay of the inhibition helped to define the IID selectivity of these cells, accounting for a significant part of the variation in selectivity among LSO cells.

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.

Anatomy and projection patterns of the superior olivary complex in the Mexican free-tailed bat, Tadarida brasiliensis mexicana.

The superior olivary complex (SOC) is the first station in the ascending auditory pathway that receives binaural projections. Two of the principal nuclei, the lateral superior olive (LSO) and the medial superior olive (MSO), are major sources of ascending projections to the inferior colliculus. Whereas almost all mammals have an LSO, it has traditionally been thought that only animals that hear low frequencies have an MSO. Recent reports, however, suggest that the medial part of the SOC in bats is highly variable and that at least some bats have a well-developed MSO. Thus, the main goal of this study was to evaluate the cytoarchitecture and connections of the principal superior olivary nuclei of the Mexican free-tailed bat, with specific attention directed at the MSO. Cell and fiber stained material revealed that the LSO and the medial nucleus of the trapezoid body (MNTB) are similar to those described for other mammals. There are two medial nuclei we refer to as dorsomedial periolivary nucleus (DMPO) and MSO. Tracer experiments exhibited that the DMPO receives bilateral projections from the cochlear nucleus, and additional projections from the ipsilateral MNTB. The DMPO sends a strong projection to the ipsilateral inferior colliculus. Positive staining for acetylcholinesterase indicates that the DMPO is a part of the olivocochlear system, as it is in other animals. The MSO in the free-tailed bat meets many of the criteria that traditionally define this nucleus. These include the presence of bipolar and multipolar principal cells, bilateral innervation from the cochlear nucleus, a strong projection from the ipsilateral MNTB, and the absence of cholinergic cells. The major difference from traditional MSO features is that it projects bilaterally to the inferior colliculus. Approximately 30% of its cells provide collateral projections to the colliculi on both sides. Functional implications of the MSO for the free-tailed bat are considered in the Discussion.