A comparison of the interaural time sensitivity of neurons in the inferior colliculus and thalamus of the unanesthetized rabbit.

The localization of low-frequency sounds (less than 3 kHz) along the azimuth involves comparing the ongoing difference in the time of arrival of a sound at the two ears. Information about interaural time differences (ITDs) is derived from an initial comparison performed in the superior olivary complex. However, little is known about which aspects of this information are transformed as it ascends the brainstem. To address this issue, we compared the ITD sensitivity of neurons in the inferior colliculus (IC) and auditory thalamus, successive stations in the auditory pathway. We found ITD sensitivity in the IC and thalamus to be similar in several respects. At both levels, the large majority of neurons responded maximally to ITDs within the range that a rabbit would normally encounter (+/- 300 microseconds) and preferred ipsilateral delays, delays that would be created by sounds in the contralateral sound field. The range of frequencies over which ITD sensitivity was expressed was also similar in the midbrain and thalamus. Several differences were also apparent. In comparison to IC neurons, neurons in the thalamus responded over more restricted ranges of ITD, responded at lower rates, and, in response to monaural stimulation, showed an increased influence of inhibition. Finally, a greater proportion of thalamic units had characteristic delays corresponding to intermediate discharge rates. The preservation of a bias for ipsilateral delays from IC to thalamus suggests that a representation of contralateral azimuths is present at both levels. Similarities between the two levels suggest that information about ITDs is faithfully transmitted from midbrain to thalamus. Differences in ITD sensitivity, such as the sharper tuning for ITDs, suggest that the thalamus is not a simple relay. Enhanced sensitivity to ITDs should translate to better-defined azimuthal receptive fields, and therefore may be a step toward achieving an optimal representation of azimuth within the auditory pathway.     

Transformation from a pure time delay to a mixed time and phase delay representation in the auditory forebrain pathway

Birds and mammals exploit interaural time differences (ITDs) for sound localization. Subsequent to ITD detection by brainstem neurons, ITD processing continues in parallel midbrain and forebrain pathways. In the barn owl, both ITD detection and processing in the midbrain are specialized to extract ITDs independent of frequency, which amounts to a pure time delay representation. Recent results have elucidated different mechanisms of ITD detection in mammals, which lead to a representation of small ITDs in high-frequency channels and large ITDs in low-frequency channels, resembling a phase delay representation. However, the detection mechanism does not prevent a change in ITD representation at higher processing stages. Here we analyze ITD tuning across frequency channels with pure tone and noise stimuli in neurons of the barn owl's auditory arcopallium, a nucleus at the endpoint of the forebrain pathway. To extend the analysis of ITD representation across frequency bands to a large neural population, we employed Fourier analysis for the spectral decomposition of ITD curves recorded with noise stimuli. This method was validated using physiological as well as model data. We found that low frequencies convey sensitivity to large ITDs, whereas high frequencies convey sensitivity to small ITDs. Moreover, different linear phase frequency regimes in the high-frequency and low-frequency ranges suggested an independent convergence of inputs from these frequency channels. Our results are consistent with ITD being remodeled toward a phase delay representation along the forebrain pathway. This indicates that sensory representations may undergo substantial reorganization, presumably in relation to specific behavioral output.     

A matter of time: internal delays in binaural processing

As an animal navigates its surroundings, the sounds reaching its two ears change in waveform similarity (interaural correlation) and in time of arrival (interaural time difference, ITD). Humans are exquisitely sensitive to these binaural cues, and it is generally agreed that this sensitivity involves coincidence detectors and internal delays that compensate for external acoustic delays (ITDs). Recent data show an unexpected relationship between the tuning of a neuron to frequency and to ITD, leading to several proposals for sources of internal delay and the neural coding of interaural temporal cues. We review the alternatives, and argue that an understanding of binaural mechanisms requires consideration of sensitivity not only to ITDs, but also to interaural correlation.     

Chronic Bilateral Cochlear Implant Stimulation Partially Restores Neural Binaural Sensitivity in Neonatally-Deaf Rabbits

Cochlear implant (CI) users with a prelingual onset of hearing loss show poor sensitivity to interaural time differences (ITDs), an important cue for sound localization and speech reception in noise. Similarly, neural ITD sensitivity in the inferior colliculus (IC) of neonatally-deafened animals is degraded compared with animals deafened as adults. Here, we show that chronic bilateral CI stimulation during development can partly reverse the effect of early-onset deafness on ITD sensitivity. The prevalence of ITD sensitive neurons was restored to the level of adult-deaf (AD) rabbits in the early-deaf rabbits of both sexes that received chronic stimulation and behavioral training with wearable bilateral sound processors during development. We also found a partial improvement in neural ITD sensitivity in the early-deaf and stimulated rabbits compared with unstimulated rabbits. In contrast, chronic CI stimulation did not improve temporal coding in early-deaf rabbits. The present study is the first report showing functional restoration of ITD sensitivity with CI stimulation in single neurons and highlights the importance of auditory experience during development on the maturation of binaural circuitry.SIGNIFICANCE STATEMENT Although cochlear implants (CI) are highly successful in providing speech reception in quiet for many profoundly deaf people, CI users still face difficulty in noisy everyday environment. This is partly because of their poor sensitivity to differences in the timing of sounds arriving at the two ears [interaural time differences (ITDs)], which help to identify where the sound is coming from. This problem is especially acute in those who lost hearing early in life. Here, we present the first report that sensitivity of auditory neurons to ITDs is restored by CI stimulation during development in an animal model of neonatal deafness. These findings highlight the importance of providing early binaural auditory experience with CIs in deaf children.     

Representation of interaural time difference in the central nucleus of the barn owl's inferior colliculus

This paper investigates the role of the central nucleus of the barn owl's inferior colliculus in determination of the sound-source azimuth. The central nucleus contains many neurons that are sensitive to interaural time difference (ITD), the cue for azimuth in the barn owl. The response of these neurons varies in a cyclic manner with the ITD of a tone or noise burst. Response maxima recur at integer multiples of the period of the stimulating tone, or, if the stimulus is noise, at integer multiples of the period corresponding to the neuron's best frequency. Such neurons can signal, by means of their relative spike rate, the phase difference between the sounds reaching the left and right ears. Since an interaural phase difference corresponds to more than one ITD, these neurons represent ITD ambiguously. We call this phenomenon phase ambiguity. The central nucleus is tonotopically organized and its neurons are narrowly tuned to frequency. Neurons in an array perpendicular to isofrequency laminae form a physiological and anatomical unit; only one ITD, the array-specific ITD, activates all neurons in an array at the same relative level. We, therefore, may say that, in the central nucleus, an ITD is conserved in an array of neurons. Array-specific ITDs are mapped and encompass the entire auditory space of the barn owl. Individual space-specific neurons of the external nucleus, which receive inputs from a wide range of frequency channels (Knudsen and Konishi, 1978), are selective for a unique ITD. Space-specific neurons do not show phase ambiguity when stimulated with noise (Takahashi and Konishi, 1986). Space-specific neurons receive inputs from arrays that are selective for the same ITD. The collective response of the neurons in an array may be the basis for the absence of phase ambiguity in space-specific neurons.     

Binaural cross-correlation and auditory localization in the barn owl: a theoretical study

The barn owl is a nocturnal predator that is able to capture mice in complete darkness using only sound to localize prey. Two binaural cues are used by the barn owl to determine the spatial position of a sound source: differences in the time of arrival of sounds at the two ears for the azimuth (interaural time differences (ITDs)) and differences in their amplitude for the elevation (interaural level differences (ILDs)). Neurophysiological investigations have revealed that two different neural pathways starting from the cochlea seem to be specialized for processing ITDs and ILDs. Much evidence suggests that in the barn owl the localization of the azimuth is based on a cross-correlation-like treatment of the auditory inputs at the two ears. In particular, in the external nucleus of the inferior colliculus (ICx), where cells are activated by specific values of ITD, neural activation has been recently observed to be dependent on some measure of the level of cross-correlation between the input auditory signals. However, it has also been observed that these neurons are less sensitive to noise than predicted by direct binaural cross-correlation. The mechanisms underlying such signal-to-noise improvement are not known. In this paper, by focusing on a model of the barn owl's neural pathway to the optic tectum dedicated to the localization of the azimuth, we study the mechanisms by which the ITD tuning of ICx units is achieved. By means of analytical examinations and computer simulations, we show that strong analogies exist between the process by which the barn owl evaluates the azimuth of a sound source and the generalized cross-correlation algorithm, one of the most robust methods for the estimate of time delays.     

Auditory processing of interaural timing information: new insights.

Differences in the time-of-arrival of sounds at the two ears, or interaural temporal disparities (ITDs), constitute one of the major binaural cues that underlie our ability to localize sounds in space. In addition, ITDs contribute to our ability to detect and to discriminate sounds, such as speech, in noisy environments. For low-frequency signals, ITDs are conveyed primarily by "cycle-by-cycle" disparities present in the fine-structure of the waveform. For high-frequency signals, ITDs are conveyed by disparities within the time-varying amplitude, or envelope, of the waveform. The results of laboratory studies conducted over the past few decades indicate that ITDs within the envelopes of high-frequency are less potent than those within the fine-structure of low-frequency stimuli. This is true for both measures of sensitivity to changes in ITD and for measures of the extent of the perceived lateral displacement of sounds containing ITDs. Colburn and Esquissaud (1976) hypothesized that it is differences in the specific aspects of the waveform that are coded neurally within each monaural (single ear) channel that account for the greater potency of ITDs at low frequencies rather than any differences in the more central binaural mechanisms that serve these different frequency regions. In this review, the results of new studies are reported that employed special high-frequency "transposed" stimuli that were designed to provide the high-frequency channels of the binaural processor with envelope-based information that mimics waveform-based information normally available only in low-frequency channels. The results demonstrate that these high-frequency transposed stimuli (1) yield sensitivity to ITDs that approaches, or is equivalent to, that obtained with "conventional" low-frequency stimuli and (2) yield large extents of laterality that are similar to those measured with conventional low-frequency stimuli. These findings suggest that by providing the high-frequency channels of the binaural processor with information that mimics that normally available only at low frequencies, the potency of ITDs in the two frequency regions can be made to be similar, if not identical. These outcomes provide strong support for Colburn and Esquissaud's (1976) hypothesis. The use of high-frequency transposed stimuli, in both behavioral and physiological investigations offers the promise of new and important insights into the nature of binaural processing.     

Selectivity for interaural time difference in the owl's midbrain

The barn owl uses the interaural difference in the timing of sounds to determine the azimuth of the source. When the sound has a wide frequency band, localization is precise. When localizing tones, however, the barn owl errs in a manner that suggests that it is confused by phantom targets. We report a neural equivalent of these phenomena as they are observed in the space-specific neuron of the owl's inferior colliculus. When stimulated with a tone, the space-specific neuron discharges maximally at interaural time differences (ITDs) that differ by one period of the stimulus tone. Changing the stimulus frequency changes the period of the ITD-response functions, but 1 ITD evokes, in most neurons, a maximal response, regardless of frequency. This ITD is the characteristic delay (CD). When stimulated with noise, there is a maximal response only to ITDs at or near the CD. Thus, the space-specific neuron can unambiguously signal the CD, provided that the signal contains more than 1 frequency. The preferential response to a single ITD, which is observed with noise stimuli, was also observed when the summed waveform of the best frequency and another tone, F2, was presented. The response of the space-specific neuron to these 2-tone stimuli could not be accounted for by the summing or averaging of the ITD-response functions obtained with the best frequency or F2 alone, suggesting that nonlinear neural processes are involved.     

The role of GABAergic inhibition in processing of interaural time difference in the owl's auditory system

The barn owl uses interaural time differences (ITDs) to localize the azimuthal position of sound. ITDs are processed by an anatomically distinct pathway in the brainstem. Neuronal selectivity for ITD is generated in the nucleus laminaris (NL) and conveyed to both the anterior portion of the ventral nucleus of the lateral lemniscus (VLVa) and the central (ICc) and external (ICx) nuclei of the inferior colliculus. With tonal stimuli, neurons in all regions are found to respond maximally not only to the real ITD, but also to ITDs that differ by integer multiples of the tonal period. This phenomenon, phase ambiguity, does not occur when ICx neurons are stimulated with noise. The main aim of this study was to determine the role of GABAergic inhibition in the processing of ITDs. Selectivity for ITD is similar in the NL and VLVa and improves in the ICc and ICx. Iontophoresis of bicuculline methiodide (BMI), a selective GABAA antagonist, decreased the ITD selectivity of ICc and ICx neurons, but did not affect that of VLVa neurons. Responses of VLVa and ICc neurons to unfavorable ITDs were below the monaural response levels. BMI raised both binaural responses to unfavorable ITDs and monaural responses, though the former remained smaller than the latter. During BMI application, ICx neurons showed phase ambiguity to noise stimuli and no longer responded to a unique ITD. BMI increased the response magnitude and changed the temporal discharge patterns in the VLVa, ICc, and ICx. Iontophoretically applied GABA exerted effects opposite to those of BMI, and the effects could be antagonized with simultaneous application of BMI. These results suggest that GABAergic inhibition (1) sharpens ITD selectivity in the ICc and ICx, (2) contributes to the elimination of phase ambiguity in the ICx, and (3) controls response magnitude and temporal characteristics in the VLVa, ICc, and ICx. Through these actions, GABAergic inhibition shapes the horizontal dimension of the auditory receptive fields.     

Relative size of auditory pathways in symmetrically and asymmetrically eared owls

Owls are highly efficient predators with a specialized auditory system designed to aid in the localization of prey. One of the most unique anatomical features of the owl auditory system is the evolution of vertically asymmetrical ears in some species, which improves their ability to localize the elevational component of a sound stimulus. In the asymmetrically eared barn owl, interaural time differences (ITD) are used to localize sounds in azimuth, whereas interaural level differences (ILD) are used to localize sounds in elevation. These two features are processed independently in two separate neural pathways that converge in the external nucleus of the inferior colliculus to form an auditory map of space. Here, we present a comparison of the relative volume of 11 auditory nuclei in both the ITD and the ILD pathways of 8 species of symmetrically and asymmetrically eared owls in order to investigate evolutionary changes in the auditory pathways in relation to ear asymmetry. Overall, our results indicate that asymmetrically eared owls have much larger auditory nuclei than owls with symmetrical ears. In asymmetrically eared owls we found that both the ITD and ILD pathways are equally enlarged, and other auditory nuclei, not directly involved in binaural comparisons, are also enlarged. We suggest that the hypertrophy of auditory nuclei in asymmetrically eared owls likely reflects both an improved ability to precisely locate sounds in space and an expansion of the hearing range. Additionally, our results suggest that the hypertrophy of nuclei that compute space may have preceded that of the expansion of the hearing range and evolutionary changes in the size of the auditory system occurred independently of phylogeny.     

The organization of frequency and binaural cues in the gerbil inferior colliculus

The inferior colliculus (IC) is the common target of separate pathways that transmit different types of auditory information. Beyond tonotopy, little is known about the organization of response properties within the 3‐dimensional layout of the auditory midbrain in most species. Through study of interaural time difference (ITD) processing, the functional properties of neurons can be readily characterized and related to specific pathways. To characterize the representation of ITDs relative to the frequency and hodological organization of the IC, the properties of neurons were recorded and the sites recovered histologically. Subdivisions of the IC were identified based on cytochrome oxidase (CO) histochemistry. The results were plotted within a framework formed by an MRI atlas of the gerbil brain. The central nucleus was composed of two parts, and lateral and dorsal cortical areas were identified. The lateral part of the central nucleus had the highest CO activity in the IC and a high proportion of neurons sensitive to ITDs. The medial portion had lower CO activity and fewer ITD‐sensitive neurons. A common tonotopy with a dorsolateral to ventromedial gradient of low to high frequencies spanned the two regions. The distribution of physiological responses was in close agreement with known patterns of ascending inputs. An understanding of the 3‐dimensional organization of the IC is needed to specify how the single tonotopic representation in the IC central nucleus leads to the multiple tonotopic representations in core areas of the auditory cortex.     

Spatial selectivity and binaural responses in the inferior colliculus of the great horned owl

In this study we have investigated the processing of auditory cues for sound localization in the great horned owl (Bubo virginianus). Previous studies have shown that the barn owl, whose ears are asymmetrically oriented in the vertical plane, has a 2-dimensional, topographic representation of auditory space in the external division of the inferior colliculus (ICx). As in the barn owl, the great horned owl's ICx is anatomically distinct and projects to the optic tectum. Neurons in ICx respond over only a small range of azimuths (mean = 32 degrees), and azimuth is topographically mapped. In contrast to the barn owl, the great horned owl has bilaterally symmetrical ears and its receptive fields are not restricted in elevation. The binaural cues available for sound localization were measured both with cochlear microphonic recordings and with a microphone attached to a probe tube in the auditory canal. Interaural time disparity (ITD) varied monotonically with azimuth. Interaural intensity differences (IID) also changed with azimuth, but the largest IIDs were less than 15 dB, and the variation was not monotonic. Neither ITD nor IID varied systematically with changes in the vertical position of a sound source. We used dichotic stimulation to determine the sensitivity of ICx neurons to these binaural cues. Best ITD of ICx units was topographically mapped and strongly correlated with receptive-field azimuth. The width of ITD tuning curves, measured at 50% of the maximum response, averaged 72 microseconds. All ICx neurons responded only to binaural stimulation and had nonmonotonic IID tuning curves. Best IID was weakly, but significantly, correlated with best ITD (r = 0.39, p less than 0.05). The IID tuning curves, however, were broad (mean 50% width = 24 dB), and 67% of the units had best IIDs within 5 dB of 0 dB IID. ITD tuning was sensitive to variations in IID in the direction opposite to that expected for time-intensity trading, but the magnitude of this effect was only 1.5 microseconds/dB IID. We conclude that, in the great horned owl, the spatial selectivity of ICx neurons arises primarily from their ITD tuning. Except for the absence of elevation selectivity and the narrow range of best IIDs, ICx in the great horned owl appears to be organized much the same as in the barn owl.     

Receptive Fields of Neurons in the Owl's Auditory Brainstem Change Dynamically

Binaural neurons in the barn owl's auditory brainstem have spatial receptive fields. It is shown here that both the frequency tuning of these neurons and their tuning to interaural time difference (ITD), the prime cue for azimuthal sound localization, improves with time after stimulus onset, a process I shall term 'dynamic sharpening'. Thus, the receptive fields of these neurons also have a temporal dimension. Data were collected in four hierachically ordered nuclei concerned with the computation of ITD: the nucleus ventralis lemnisci lateralis, pars anterior (VLVa), and three subnuclei in the inferior colliculus. Dynamic sharpening in the frequency tuning curves is evident from a dynamic reduction of tuning width. When stimulated with a tone, the response of all neurons varies in a cyclic manner with ITD. The ITDs at the response peaks differ by one period of the stimulus tone. The responses with noise stimulation are similar to the responses with tonal stimulation in all but the hierarchically highest nucleus, the external nucleus of the inferior colliculus. In this nucleus are found neurons that, if stimulated with noise, respond maximally only to one ITD while the responses at the other peaks are suppressed. This sidepeak suppression is a dynamic process. Dynamic sharpening of ITD tuning is also evident from a dynamic reduction of the tuning width around each of the response peaks. The proportion of neurons showing dynamic sharpening of ITD tuning is the same in all collicular subnuclei, but is lower in VLVa. Therefore, a major component of dynamic sharpening of ITD tuning occurs at the first station of the inferior colliculus. Lateral inhibition is one of the mechanisms underlying dynamic sharpening. Part of the inhibition may be mediated by GABA (Fujita and Konishi, 1988). The function of dynamic sharpening of ITD tuning may be to increase the fine representation of auditory space in single neurons.     

Physiological Diversity Influences Detection of Stimulus Envelope and Fine Structure in Neurons of the Medial Superior Olive

The neurons of the medial superior olive (MSO) of mammals extract azimuthal information from the delays between sounds reaching the two ears [interaural time differences (ITDs)]. Traditionally, all models of sound localization have assumed that MSO neurons represent a single population of cells with specialized and homogeneous intrinsic and synaptic properties that enable the detection of synaptic coincidence on a timescale of tens to hundreds of microseconds. Here, using patch-clamp recordings from large populations of anatomically labeled neurons in brainstem slices from male and female Mongolian gerbils (Meriones unguiculatus), we show that MSO neurons are far more physiologically diverse than previously appreciated, with properties that depend regionally on cell position along the topographic map of frequency. Despite exhibiting a similar morphology, neurons in the MSO exhibit subthreshold oscillations of differing magnitudes that drive action potentials at rates between 100 and 800 Hz. These oscillations are driven primarily by voltage-gated sodium channels and are distinct from resonant properties derived from other active membrane properties. We show that graded differences in these and other physiological properties across the MSO neuron population enable the MSO to duplex the encoding of ITD information in both fast, submillisecond time-varying signals as well as in slower envelopes.SIGNIFICANCE STATEMENT Neurons in the medial superior olive (MSO) encode sound localization cues by detecting microsecond differences in the arrival times of inputs from the left and right ears, and it has been assumed that this computation is made possible by highly stereotyped structural and physiological specializations. Here we report using a large (>400) sample size in which MSO neurons show a strikingly large continuum of functional properties despite exhibiting similar morphologies. We demonstrate that subthreshold oscillations mediated by voltage-gated Na⁺ channels play a key role in conferring graded differences in firing properties. This functional diversity likely confers capabilities of processing both fast, submillisecond-scale synaptic activity (acoustic “fine structure”), and slow-rising envelope information that is found in amplitude-modulated sounds and speech patterns.     

Behavioural sensitivity to binaural spatial cues in ferrets: evidence for plasticity in the duplex theory of sound localization

For over a century, the duplex theory has guided our understanding of human sound localization in the horizontal plane. According to this theory, the auditory system uses interaural time differences (ITDs) and interaural level differences (ILDs) to localize low‐frequency and high‐frequency sounds, respectively. Whilst this theory successfully accounts for the localization of tones by humans, some species show very different behaviour. Ferrets are widely used for studying both clinical and fundamental aspects of spatial hearing, but it is not known whether the duplex theory applies to this species or, if so, to what extent the frequency range over which each binaural cue is used depends on acoustical or neurophysiological factors. To address these issues, we trained ferrets to lateralize tones presented over earphones and found that the frequency dependence of ITD and ILD sensitivity broadly paralleled that observed in humans. Compared with humans, however, the transition between ITD and ILD sensitivity was shifted toward higher frequencies. We found that the frequency dependence of ITD sensitivity in ferrets can partially be accounted for by acoustical factors, although neurophysiological mechanisms are also likely to be involved. Moreover, we show that binaural cue sensitivity can be shaped by experience, as training ferrets on a 1‐kHz ILD task resulted in significant improvements in thresholds that were specific to the trained cue and frequency. Our results provide new insights into the factors limiting the use of different sound localization cues and highlight the importance of sensory experience in shaping the underlying neural mechanisms.     

Binaural responses in the auditory midbrain of chicken (Gallus gallus)

The auditory midbrain is the location in which neurons represent binaural acoustic information necessary for sound localization. The external nucleus of the midbrain inferior colliculus (IC) of the barn owl is a classic example of an auditory space map, but it is unknown to what extent the principles underlying its formation generalize to other, less specialized animals. We characterized the spiking responses of 139 auditory neurons in the IC of the chicken (Gallus gallus) in vivo, focusing on their sensitivities to the binaural localization cues of interaural time (ITD) and level (ILD) differences. Most units were frequency‐selective, with best frequencies distributed unevenly into low‐frequency and high‐frequency (> 2 kHz) clusters. Many units showed sensitivity to either ITD (65%) or ILD (66%) and nearly half to both (47%). ITD selectivity was disproportionately more common among low‐frequency units, while ILD‐only selective units were predominantly tuned to high frequencies. ILD sensitivities were diverse, and we thus developed a decision tree defining five types. One rare type with a bell‐like ILD tuning was also selective for ITD but typically not frequency‐selective, and thus matched the characteristics of neurons in the auditory space map of the barn owl. Our results suggest that generalist birds such as the chicken show a prominent representation of ITD and ILD cues in the IC, providing complementary information for sound localization, according to the duplex theory. A broadband response type narrowly selective for both ITD and ILD may form the basis for a representation of auditory space.     

Interaural timing difference circuits in the auditory brainstem of the emu (Dromaius novaehollandiae)

In the auditory system, precise encoding of temporal information is critical for sound localization, a task with direct behavioral relevance. Interaural timing differences (ITDs) are computed using axonal delay lines and cellular coincidence detectors in nucleus laminaris (NL). We present morphological and physiological data on the timing circuits in the emu, Dromaius novaehollandiae, and compare these results with those from the barn owl (Tyto alba) and the domestic chick (Gallus gallus). Emu NL was composed of a compact monolayer of bitufted neurons whose two thick primary dendrites were oriented dorsoventrally. They showed a gradient in dendritic length along the presumed tonotopic axis. The NL and nucleus magnocellularis (NM) neurons were strongly immunoreactive for parvalbumin, a calcium-binding protein. Antibodies against synaptic vesicle protein 2 and glutamic acid decarboxlyase revealed that excitatory synapses terminated heavily on the dendritic tufts, while inhibitory terminals were distributed more uniformly. Physiological recordings from brainstem slices demonstrated contralateral delay lines from NM to NL. During whole-cell patch-clamp recordings, NM and NL neurons fired single spikes and were doubly rectifying. NL and NM neurons had input resistances of 30.0 +/- 19.9 Momega and 49.0 +/- 25.6 Momega, respectively, and membrane time constants of 12.8 +/- 3.8 ms and 3.9 +/- 0.2 ms. These results provide further support for the Jeffress model for sound localization in birds. The emu timing circuits showed the ancestral (plesiomorphic) pattern in their anatomy and physiology, while differences in dendritic structure compared to chick and owl may indicate specialization for encoding ITDs at low best frequencies.     

Topography and morphology of the inhibitory projection from superior olivary nucleus to nucleus laminaris in chickens (Gallus gallus)

The avian nucleus laminaris (NL) is involved in computation of interaural time differences (ITDs) that encode the azimuthal position of a sound source. Neurons in NL are bipolar, with dorsal and ventral dendritic arbors receiving input from separate ears. NL neurons act as coincidence detectors that respond maximally when input from each ear arrives at the two dendritic arbors simultaneously. Computational and physiological studies demonstrated that the sensitivity of NL neurons to coincident inputs is modulated by an inhibitory feedback circuit via the superior olivary nucleus (SON). To understand the mechanism of this modulation, the topography of the projection from SON to NL was mapped, and the morphology of the axon terminals of SON neurons in NL was examined in chickens (Gallus gallus). In vivo injection of AlexaFluor 568 dextran amine into SON demonstrated a coarse topographic projection from SON to NL. Retrogradely labeled neurons in NL were located within the zone of anterogradely labeled terminals, suggesting a reciprocal projection between SON to NL. In vivo extracellular physiological recording further demonstrated that this topography is consistent with tonotopic maps in SON and NL. In addition, three-dimensional reconstruction of single SON axon branches within NL revealed that individual SON neurons innervate a large area of NL and terminate on both dorsal and ventral dendritic arbors of NL neurons. The organization of the projection from SON to NL supports its proposed functions of controlling the overall activity level of NL and enhancing the specificity of frequency mapping and ITD detection.     

Responses of neurons in the inferior colliculus to binaural disparities: insights from the use of Fisher information and mutual information

The minimal change in a stimulus property that is detectable by neurons has been often quantified using the receiver operating characteristic (ROC) curve, but recent studies introduced the use of the related Fisher information (FI). Whereas ROC analysis and FI quantify the information available for discriminating between two stimuli, global aspects of the information carried by a neuron are quantified by the mutual information (MI) between stimuli and responses. FI and MI have been shown to be related to each other when FI is large. Here the responses of neurons recorded in the inferior colliculus of anesthetized guinea pigs in response to ensembles of sounds differing in their interaural time differences (ITDs) or binaural correlation (BC) were analyzed. Although the FI is not uniformly large, there are strong relationships between MI and FI. Information-theoretic measures are used to demonstrate the importance of the non-Poisson statistics of these responses. These neurons may reflect the maximization of the MI between stimuli and responses under constraints on the coded stimulus range and the range of firing rates. Remarkably, whereas the maximization of MI, in conjunction with the non-Poisson statistics of the spike trains, is enough to create neurons whose ITD discrimination capabilities are close to the behavioral limits, the same rule does not achieve single-neuron BC discrimination that is as close to behavioral performance.