Head-related transfer functions of rabbits within the front horizontal plane.

The head-related transfer function (HRTF) describes the direction-dependent acoustic filtering by the head that occurs between a source signal in free-field space and the signal at the tympanic membrane. HRTFs contain information on sound source location via interaural differences of their magnitude or phase spectra and via the shapes of their magnitude spectra. The present study characterized HRTFs for source locations in the front horizontal plane for nine rabbits, which are a species commonly used in studies of the central auditory system. HRTF magnitude spectra shared several features across individuals, including a broad spectral peak at 2.6kHz that increased gain by 12 to 23dB depending on source azimuth; and a notch at 7.6kHz and peak at 9.8kHz visible for most azimuths. Overall, frequencies above 4kHz were amplified for sources ipsilateral to the ear and progressively attenuated for frontal and contralateral azimuths. The slope of the magnitude spectrum between 3 and 5kHz was found to be an unambiguous monaural cue for source azimuths ipsilateral to the ear. Average interaural level difference (ILD) between 5 and 16kHz varied monotonically with azimuth over ±31dB despite a relatively small head size. Interaural time differences (ITDs) at 0.5kHz and 1.5kHz also varied monotonically with azimuth over ±358 µs and ±260 µs, respectively. Remeasurement of HRTFs after pinna removal revealed that the large pinnae of rabbits were responsible for all spectral peaks and notches in magnitude spectra and were the main contribution to high-frequency ILDs (5-16kHz), whereas the rest of the head was the main contribution to ITDs and low-frequency ILDs (0.2-1.5kHz). Lastly, inter-individual differences in magnitude spectra were found to be small enough that deviations of individual HRTFs from an average HRTF were comparable in size to measurement error. Therefore, the average HRTF may be acceptable for use in neural or behavioral studies of rabbits implementing virtual acoustic space when measurement of individualized HRTFs is not possible.

Head-related transfer functions of rabbits within the front horizontal plane.

The head-related transfer function (HRTF) is the direction-dependent acoustic filtering by the head that occurs between a source signal in free-field space and the signal at the tympanic membrane. HRTFs contain information on sound source location via interaural differences of their magnitude or phase spectra and via the shapes of their magnitude spectra. The present study characterized HRTFs for source locations in the front horizontal plane for nine rabbits, which are a species commonly used in studies of the central auditory system. HRTF magnitude spectra shared several features across individuals, including a broad spectral peak at 2.6 kHz that increased gain by 12 to 23 dB depending on source azimuth; and a notch at 7.6 kHz and peak at 9.8 kHz visible for most azimuths. Overall, frequencies above 4 kHz were amplified for sources ipsilateral to the ear and progressively attenuated for frontal and contralateral azimuths. The slope of the magnitude spectrum between 3 and 5 kHz was found to be an unambiguous monaural cue for source azimuths ipsilateral to the ear. Average interaural level difference (ILD) between 5 and 16 kHz varied monotonically with azimuth over ±31 dB despite a relatively small head size. Interaural time differences (ITDs) at 0.5 kHz and 1.5 kHz also varied monotonically with azimuth over ±358 µs and ±260 µs, respectively. Remeasurement of HRTFs after pinna removal revealed that the large pinnae of rabbits were responsible for all spectral peaks and notches in magnitude spectra and were the main contribution to high-frequency ILDs, whereas the rest of the head was the main contribution to ITDs and low-frequency ILDs. Lastly, inter-individual differences in magnitude spectra were found to be small enough that deviations of individual HRTFs from an average HRTF were comparable in size to measurement error. Therefore, the average HRTF may be acceptable for use in neural or behavioral studies of rabbits implementing virtual acoustic space when measurement of individualized HRTFs is not possible.

Specific loss of neural sensitivity to interaural time difference of unmodulated noise stimuli following noise-induced hearing loss.

Sensorineural hearing loss (SNHL) causes an overall deficit in binaural hearing, including the abilities to localize sound sources, discriminate interaural time and level differences (ITDs and ILDs, respectively), and utilize binaural cues to aid signal detection and comprehension in noisy environments. Few studies have examined the effect of SNHL on binaural coding in the central auditory system, and those that have focused on age-related hearing loss. We induced hearing loss in male and female Dutch-belted rabbits via noise overexposure and compared unanesthetized single-unit responses of their inferior colliculi [hearing loss (HL) neurons] with those of unexposed rabbits. Sound-level thresholds of HL neurons to diotic noise were elevated by 75 dB, on average. Sensitivity of firing rates of HL neurons to the azimuth of a broadband noise stimulus was reduced, on average, but was confounded by differences in sound level with respect to detection threshold between groups. We independently manipulated ITD and ILD in virtual acoustic space and found directional sensitivity in binaurally sensitive HL neurons was entirely due to ILD sensitivity and no different than that for unexposed rabbits. However, ITD sensitivity was completely absent in binaurally sensitive HL neurons for noise stimuli both in virtual acoustic space and with ITDs extending to ±3 ms. HL neurons also had weaker spike-timing precision and slightly increased spontaneous rates. Overall, ILD sensitivity was uncompromised, whereas ITD sensitivity was completely lost, implying a specific inability to use information in the timing or correlation of acoustic noise waveforms between the two ears following severe SNHL.NEW & NOTEWORTHY Sensorineural hearing loss compromises perceptual abilities that arise from hearing with two ears, yet its effects on binaural aspects of neural responses are largely unknown. We found that, following severe hearing loss because of acoustic trauma, auditory midbrain neurons specifically lost the ability to encode time differences between the arrival of a broadband noise stimulus to the two ears, whereas the encoding of sound level differences between the two ears remained uncompromised.

Stimulus-frequency-dependent dominance of sound localization cues across the cochleotopic map of the inferior colliculus.

The horizontal direction of a sound source (i.e., azimuth) is perceptually determined in a frequency-dependent manner: low- and high-frequency sounds are localized via differences in the arrival time and intensity of the sound at the two ears, respectively, called interaural time and level differences (ITDs and ILDs). In the central auditory system, these binaural cues to direction are thought to be separately encoded by neurons tuned to low and high characteristic frequencies (CFs). However, at high sound levels a neuron often responds to frequencies far from its CF, raising the possibility that individual neurons may encode the azimuths of both low- and high-frequency sounds using both binaural cues. We tested this possibility by measuring auditory-driven single-unit responses in the central nucleus of the inferior colliculus (ICC) of unanesthetized female Dutch Belted rabbits with a multitetrode drive. At 70 dB SPL, ICC neurons across the cochleotopic map transmitted information in their firing rates about the direction of both low- and high-frequency noise stimuli. We independently manipulated ITD and ILD cues in virtual acoustic space and found that sensitivity to ITD and ILD, respectively, shaped the directional sensitivity of ICC neurons to low (<1.5 kHz)- and high (>3 kHz)-pass stimuli, regardless of the neuron's CF. We also found evidence that high-CF neurons transmit information about both the fine-structure and envelope ITD of low-frequency sound. Our results indicate that at conversational sound levels the majority of the cochleotopic map is engaged in transmitting directional information, even for sources with narrowband spectra.NEW & NOTEWORTHY A "division of labor" has previously been assumed in which the directions of low- and high-frequency sound sources are thought to be encoded by neurons preferentially sensitive to low and high frequencies, respectively. Contrary to this, we found that auditory midbrain neurons encode the directions of both low- and high-frequency sounds regardless of their preferred frequencies. Neural responses were shaped by different sound localization cues depending on the stimulus spectrum-even within the same neuron.

Paired measurements of cochlear function and hair cell count in Dutch-belted rabbits with noise-induced hearing loss.

The effects of noise-induced hearing loss have yet to be studied for the Dutch-belted strain of rabbits, which is the only strain that has been used in studies of the central auditory system. We measured auditory brainstem responses (ABRs), 2f1-f2 distortion product otoacoustic emissions (DPOAEs), and counts of cochlear inner and outer hair cells (IHCs and OHCs, respectively) from confocal images of Myo7a-stained cochlear whole-mounts in unexposed and noise-overexposed, Dutch-belted, male and female rabbits in order to characterize cochlear function and structure under normal-hearing and hearing-loss conditions. Using an octave-band noise exposure centered at 750 Hz presented under isoflurane anesthesia, we found that a sound level of 133 dB SPL for 60 min was minimally sufficient to produce permanent ABR threshold shifts. Overexposure durations of 60 and 90 min caused median click-evoked ABR threshold shifts of 10 and 50 dB, respectively. Susceptibility to overexposure was highly variable across ears, but less variable across test frequencies within the same ear. ABR and DPOAE threshold shifts were smaller, on average, and more variable in male than female ears. Similarly, post-exposure survival of OHCs was higher, on average, and more variable in male than female ears. We paired post-exposure ABR and DPOAE threshold shift data with hair cell count data measured in the same ear at the same frequency and cochlear frequency location. ABR and DPOAE threshold shifts exhibited critical values of 46 and 18 dB, respectively, below which the majority of OHCs and IHCs survived and above which OHCs were wiped out while IHC survival was variable. Our data may be of use to researchers who wish to use Dutch-belted rabbits as a model for the effects of noise-induced hearing loss on the central auditory system.

Neural population encoding and decoding of sound source location across sound level in the rabbit inferior colliculus.

At lower levels of sensory processing, the representation of a stimulus feature in the response of a neural population can vary in complex ways across different stimulus intensities, potentially changing the amount of feature-relevant information in the response. How higher-level neural circuits could implement feature decoding computations that compensate for these intensity-dependent variations remains unclear. Here we focused on neurons in the inferior colliculus (IC) of unanesthetized rabbits, whose firing rates are sensitive to both the azimuthal position of a sound source and its sound level. We found that the azimuth tuning curves of an IC neuron at different sound levels tend to be linear transformations of each other. These transformations could either increase or decrease the mutual information between source azimuth and spike count with increasing level for individual neurons, yet population azimuthal information remained constant across the absolute sound levels tested (35, 50, and 65 dB SPL), as inferred from the performance of a maximum-likelihood neural population decoder. We harnessed evidence of level-dependent linear transformations to reduce the number of free parameters in the creation of an accurate cross-level population decoder of azimuth. Interestingly, this decoder predicts monotonic azimuth tuning curves, broadly sensitive to contralateral azimuths, in neurons at higher levels in the auditory pathway.

Decoding sound source location and separation using neural population activity patterns.

The strategies by which the central nervous system decodes the properties of sensory stimuli, such as sound source location, from the responses of a population of neurons are a matter of debate. We show, using the average firing rates of neurons in the inferior colliculus (IC) of awake rabbits, that prevailing decoding models of sound localization (summed population activity and the population vector) fail to localize sources accurately due to heterogeneity in azimuth tuning across the population. In contrast, a maximum-likelihood decoder operating on the pattern of activity across the population of neurons in one IC accurately localized sound sources in the contralateral hemifield, consistent with lesion studies, and did so with a precision consistent with rabbit psychophysical performance. The pattern decoder also predicts behavior in response to incongruent localization cues consistent with the long-standing "duplex" theory of sound localization. We further show that the pattern decoder accurately distinguishes two concurrent, spatially separated sources from a single source, consistent with human behavior. Decoder detection of small amounts of source separation directly in front is due to neural sensitivity to the interaural decorrelation of sound, at both low and high frequencies. The distinct patterns of IC activity between single and separated sound sources thereby provide a neural correlate for the ability to segregate and localize sources in everyday, multisource environments.

Neural correlates of the perception of sound source separation.

As two sound sources become spatially separated in the horizontal plane, the binaural cues used for sound localization become distorted from their values for each sound in isolation. Because firing rates of most neurons in the inferior colliculus (IC) are sensitive to these binaural cues, we hypothesized that these neurons would be sensitive to source separation. We examined changes in the target azimuth tuning functions of IC neurons in unanesthetized rabbits caused by the concurrent presentation of an interferer at a fixed spatial location. Both target and interferer were broadband noise bursts, uncorrelated with each other. Signal detection analysis of firing rates of individual IC neurons shows that responses are correlated with psychophysical performance on segregation of spatially separated sources. The analysis also highlights the role of neural sensitivity to interaural time differences of cochlea-induced envelopes in performing this task. Psychophysical performance on source segregation was also compared to the performance of two contrasting ­maximum-likelihood classifiers operating on the firing rates of the population of IC ­neurons. The "population-pattern" classifier had access to the firing rates of every neuron in the population, while the "two-channel" classifier operated on the summed firing rates from each side of the brain. Unlike the two-channel classifier, the ­population-pattern classifier could segregate the sources accurately, suggesting that some of the information contained in the heterogeneity of azimuth tuning functions across IC neurons is used to segregate sources.

Neural encoding of sound source location in the presence of a concurrent, spatially separated source.

In the presence of multiple, spatially separated sound sources, the binaural cues used for sound localization in the horizontal plane become distorted from the cues from each sound in isolation, yet localization in everyday multisource acoustic environments remains robust. We examined changes in the azimuth tuning functions of inferior colliculus (IC) neurons in unanesthetized rabbits to a target broadband noise when a concurrent broadband noise interferer was presented at different locations in virtual acoustic space. The presence of an interferer generally degraded sensitivity to target azimuth and distorted the shape of the tuning function, yet most neurons remained significantly sensitive to target azimuth and maintained tuning function shapes somewhat similar to those for the target alone. Using binaural cue manipulations in virtual acoustic space, we found that single-source tuning functions of neurons with high best frequencies (BFs) were primarily determined by interaural level differences (ILDs) or monaural level, with a small influence of interaural time differences (ITDs) in some neurons. However, with a centrally located interferer, the tuning functions of most high-BF neurons were strongly influenced by ITDs as well as ILDs. Model-based analysis showed that the shapes of these tuning functions were in part produced by decorrelation of the left and right cochlea-induced envelopes that occurs with source separation. The strong influence of ITD on the tuning functions of high-BF neurons poses a challenge to the "duplex theory" of sound localization and suggests that ITD may be important for localizing high-frequency sounds in multisource environments.

Frequency-dependent interaural delays in the medial superior olive: implications for interaural cochlear delays.

Neurons in the medial superior olive (MSO) are tuned to the interaural time difference (ITD) of sound arriving at the two ears. MSO neurons evoke a strongest response at their best delay (BD), at which the internal delay between bilateral inputs to MSO matches the external ITD. We performed extracellular recordings in the superior olivary complex of the anesthetized gerbil and found a majority of single units localized to the MSO to exhibit BDs that shifted with tone frequency. The relation of best interaural phase difference to tone frequency revealed nonlinearities in some MSO units and others with linear relations with characteristic phase between 0.4 and 0.6 cycles. The latter is usually associated with the interaction of ipsilateral excitation and contralateral inhibition, as in the lateral superior olive, yet all MSO units exhibited evidence of bilateral excitation. Interaural cochlear delays and phase-locked contralateral inhibition are two mechanisms of internal delay that have been suggested to create frequency-dependent delays. Best interaural phase-frequency relations were compared with a cross-correlation model of MSO that incorporated interaural cochlear delays and an additional frequency-independent delay component. The model with interaural cochlear delay fit phase-frequency relations exhibiting frequency-dependent delays with precision. Another model of MSO incorporating inhibition based on realistic biophysical parameters could not reproduce observed frequency-dependent delays.

Subthreshold K+ channel dynamics interact with stimulus spectrum to influence temporal coding in an auditory brain stem model.

Neurons in the auditory brain stem encode signals with exceptional temporal precision. A low-threshold potassium current, IKLT, present in many auditory brain stem structures and thought to enhance temporal encoding, facilitates spike selection of rapid input current transients through an associated dynamic gate. Whether the dynamic nature of IKLT interacts with the timescales in spectrally rich input to influence spike encoding remains unclear. We examine the general influence of IKLT on spike encoding of stochastic stimuli using a pattern classification analysis between spike responses from a ventral cochlear nucleus (VCN) model containing IKLT, and the same model with the IKLT dynamics removed. The influence of IKLT on spike encoding depended on the spectral content of the current stimulus such that maximal IKLT influence occurred for stimuli with power concentrated at frequencies low enough (<500 Hz) to allow IKLT activation. Further, broadband stimuli significantly decreased the influence of IKLT on spike encoding, suggesting that broadband stimuli are not well suited for investigating the influence of some dynamic membrane nonlinearities. Finally, pattern classification on spike responses was performed for physiologically realistic conductance stimuli created from various sounds filtered through an auditory nerve (AN) model. Regardless of the sound, the synaptic input arriving at VCN had similar low-pass power spectra, which led to a large influence of IKLT on spike encoding, suggesting that the subthreshold dynamics of IKLT plays a significant role in shaping the response of real auditory brain stem neurons.