Interaural Time Difference Tuning Research Articles

Neural ITD coding with bilateral cochlear implants: effect of binaurally coherent jitter

Poor sensitivity to the interaural time difference (ITD) constrains the ability of human bilateral cochlear implant users to listen in everyday noisy acoustic environments. ITD sensitivity to periodic pulse trains degrades sharply with increasing pulse rate but can be restored at high pulse rates by jittering the interpulse intervals in a binaurally coherent manner (Laback and Majdak. Binaural jitter improves interaural time-difference sensitivity of cochlear implantees at high pulse rates. Proc Natl Acad Sci USA 105: 814-817, 2008). We investigated the neural basis of the jitter effect by recording from single inferior colliculus (IC) neurons in bilaterally implanted, anesthetized cats. Neural responses to trains of biphasic pulses were measured as a function of pulse rate, jitter, and ITD. An effect of jitter on neural responses was most prominent for pulse rates above 300 pulses/s. High-rate periodic trains evoked only an onset response in most IC neurons, but introducing jitter increased ongoing firing rates in about half of these neurons. Neurons that had sustained responses to jittered high-rate pulse trains showed ITD tuning comparable with that produced by low-rate periodic pulse trains. Thus, jitter appears to improve neural ITD sensitivity by restoring sustained firing in many IC neurons. The effect of jitter on IC responses is qualitatively consistent with human psychophysics. Action potentials tended to occur reproducibly at sparse, preferred times across repeated presentations of high-rate jittered pulse trains. Spike triggered averaging of responses to jittered pulse trains revealed that firing was triggered by very short interpulse intervals. This suggests it may be possible to restore ITD sensitivity to periodic carriers by simply inserting short interpulse intervals at select times.

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.

Effect of instantaneous frequency glides on interaural time difference processing by auditory coincidence detectors

Detecting interaural time difference (ITD) is crucial for sound localization. The temporal accuracy required to detect ITD, and how ITD is initially encoded, continue to puzzle scientists. A fundamental question is whether the monaural inputs to the binaural ITD detectors differ only in their timing, when temporal and spectral tunings are largely inseparable in the auditory pathway. Here, we investigate the spectrotemporal selectivity of the monaural inputs to ITD detector neurons of the owl. We found that these inputs are selective for instantaneous frequency glides. Modeling shows that ITD tuning depends strongly on whether the monaural inputs are spectrotemporally matched, an effect that may generalize to mammals. We compare the spectrotemporal selectivity of monaural inputs of ITD detector neurons in vivo, demonstrating that their selectivity matches. Finally, we show that this refinement can develop through spike timing-dependent plasticity. Our findings raise the unexplored issue of time-dependent frequency tuning in auditory coincidence detectors and offer a unifying perspective.

Neural Development of Binaural Tuning through Hebbian Learning Predicts Frequency-Dependent Best Delays

Birds use microsecond differences in the arrival times of the sounds at the two ears to infer the location of a sound source in the horizontal plane. These interaural time differences (ITDs) are encoded by binaural neurons which fire more when the ITD matches their "best delay." In the textbook model of sound localization, the best delays of binaural neurons reflect the differences in axonal delays of their monaural inputs, but recent observations have cast doubts on this classical view because best delays were found to depend on preferred frequency. Here, we show that these observations are in fact consistent with the notion that best delays are created by differences in axonal delays, provided ITD tuning is created during development through spike-timing-dependent plasticity: basilar membrane filtering results in correlations between inputs to binaural neurons, which impact the selection of synapses during development, leading to the observed distribution of best delays.

A developmental explanation of the dependence of binaural best delays on characteristic frequency

Both mammals and birds use interaural time difference (ITD) as a cue to determine the horizontal position of a sound source in space. In the barn owl brainstem, neurons of the Nucleus Laminaris (NL) have firing curves which vary with the acoustic stimulus ITD. Each NL neuron is tuned to a certain ITD in that their response is maximal for a certain ITD, i.e., they respond preferably when the stimuli from the two ears have a certain delay, called best delay (BD) of that neuron. Recently, it has been shown that the distribution of BDs along the tonotopical axis depends on the best frequency (BF) of their corresponding neurons. In particular, BDs rarely exceed 1/(2BF), an approximate constraint called the pi-limit. The origin of this BF-dependent distribution of BDs is still a matter of debate. In this work, we use a modeling approach to test whether the pi-limit could emerge from activity-driven plasticity, in particular Spike-Timing Dependent Plasticity (STDP). Using a standard peripheral model and physiologically plausible spiking neuron models, we first feed binaural acoustic noise with ITDs in the physiological range of the barn owl (smaller than 250 µs) to NL neurons undergoing STDP and analyze the distribution of the resulting BDs. We show that STDP selects the inputs based on their synaptic delays and that the resulting BD distribution mainly falls between plus or minus half the characteristic period of the corresponding neurons. We then use uncorrelated binaural white noises and show that the ITD selectivity and the dependence of binaural best delays on characteristic frequency also emerges after a simulated developmental period. We finally check that our conclusions also hold in more realistic settings, by feeding the model with real forest recordings. In conclusion, our results suggest that the frequency-dependence of BDs may simply be a by-product of the way ITD tuning develops in binaural neurons. It does not impair the ability of these neurons to represent the azimuth of sound sources, because BDs that differ by an integer number of characteristic periods are mostly redundant. Perhaps more interestingly, it also provides a complete representation of ITDs which is functional in any acoustical environment, even if the head of the animal continues to grow after the critical development period. This suggests that the distribution of BDs does not simply mirror the statistics of binaural sounds during development, but instead provides a robust representation of changing environments.

Tonotopic gradients in neural interaural time difference processing: A modeling study of the medial superior olive.

The interaural time difference (ITD) is the primary cue for sound localization; yet many basic questions about the biophysical mechanisms remain. In the mammalian auditory system, neurons in the medial superior olive (MSO) are tuned to ITD as well as frequency. In this study, the effects of key parameters in MSO models, such as the membrane time constants and the number and strength of synaptic inputs on ITD sensitivity to pure tones, were explored with particular attention to the best-frequency dependence of these parameters. Results show that ITD tuning is dependent on neuron membrane characteristics (i.e., the shape and time constant of the membrane response), on the strength of individual synaptic inputs, and on stimulus properties such as frequency and intensity. Models with slow response times and weak synaptic inputs show good ITD sensitivity for low-frequency tones, whereas models with fast response times and strong synaptic inputs exhibit good ITD tuning for high-frequency tones. This dependence of ITD sensitivity on membrane properties in the model suggests that parameters important for ITD tuning depend on the best frequency of the neurons, in contrast to the view that the binaural mechanism is homogeneous along the tonotopic axis.

Spike-Based Population Coding of Interaural Time Difference (ITD).

Event Abstract Back to Event Spike-Based Population Coding of Interaural Time Difference (ITD). Adrien Jouary1, 2* and Sophie Deneve1, 2 1 Ecole Normal Supérieure, Département d’Etudes Cognitives, France 2 Ecole Normal Supérieure, Inserm U960, France The interaural time difference (ITD), the difference arrival time of a sound between two ears is the primary auditory cue used by both mammals and birds to localize the source of low-frequency sounds. The minimal ITDs that barn owls or human can perceive (<10s) is two order of magnitude smaller than the duration of an action potential. It represents thus a great challenge in temporal processing. In birds, ITDs are first encoded in neurons of the nucleus laminaris (NL), thought to compute a cross-correlation of inputs from the two ears. However, while initially time-locked to the stimulus and frequency-selective, this information is eventually translated into a representation of object position in the Inferior Colliculus (IC). The neural mechanisms involved in extracting ITDs have been extensively studied, but how these responses are translated into reliable spatial positions remains unclear. To investigate this issue, we implemented a 3 layer neural network, modeling NL, ICX and IC respectively, and acting as an ideal observer. Inputs to the network are band pass-filtered signals mimicking inputs from auditory nerve fibers. Each layer, from model NL cells to ICX to inferior colliculus, performs an optimal Bayesian inference of object position based on information from the layer below. Integrate and fire dynamics and lateral inhibitory connections insure that the posterior probability distribution is optimally encoded in the output spike trains. The network output is a spiking probabilistic population code for position that can be optimally combined with information from other sources, i.e. visual cues in IC. This model reproduces a very large set of experimental results, including cross-correlation in NL, spike trains initially time locked and later asynchronous and Poisson-like, shapes, distribution and variability of ITD tuning curves in the different areas. Moreover, our approach explains how an invariant position can be extracted from different auditory signals (pure tone, noise, clicks…) corresponding to different ITD tuning curves. Each spike is associated with an invariant kernel imposed by the network connections, and decoding corresponds to a sum of these kernels. However, neural responses themselves are strongly stimulus dependent since different types of sounds are variously informative, corresponding to different probability distributions. Keywords: computational neuroscience Conference: Bernstein Conference on Computational Neuroscience, Berlin, Germany, 27 Sep - 1 Oct, 2010. Presentation Type: Presentation Topic: Bernstein Conference on Computational Neuroscience Citation: Jouary A and Deneve S (2010). Spike-Based Population Coding of Interaural Time Difference (ITD).. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference on Computational Neuroscience. doi: 10.3389/conf.fncom.2010.51.00007 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Sep 2010; Published Online: 22 Sep 2010. * Correspondence: Dr. Adrien Jouary, Ecole Normal Supérieure, Département d’Etudes Cognitives, Paris, France, adrien.jouary@ens-cachan.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Adrien Jouary Sophie Deneve Google Adrien Jouary Sophie Deneve Google Scholar Adrien Jouary Sophie Deneve PubMed Adrien Jouary Sophie Deneve Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Sound-Intensity-Dependent Compensation for the Small Interaural Time Difference Cue for Sound Source Localization

Interaural time difference (ITD) is a major cue for sound source localization. However, animals with small heads experience small ITDs, making ITD detection difficult, particularly for low-frequency sound. Here, we describe a sound-intensity-dependent mechanism for compensating for the small ITD cues in the coincidence detector neurons in the nucleus laminaris (NL) of the chicken aged from 3 to 29 d after hatching. The hypothesized compensation mechanisms were confirmed by simulation. In vivo single-unit recordings revealed an improved contrast of ITD tuning in low-best-frequency (<1 kHz) NL neurons by suppressing the firing activity at the worst ITD, whereas the firing rate was increased with increasing sound intensity at the best ITD. In contrast, level-dependent suppression was so weak in the middle- and high-best-frequency (> or =1 kHz) NL neurons that loud sounds led to increases in firing rate at both the best and the worst ITDs. The suppression of firing activity at the worst ITD in the low-best-frequency neurons required the activation of the superior olivary nucleus (SON) and was eliminated by electrolytic lesions of the SON. The frequency-dependent suppression reflected the dense projection from the SON to the low-frequency region of NL. Thus, the small ITD cues available in low-frequency sounds were partly compensated for by a sound-intensity-dependent inhibition from the SON.

Variability Reduction in Interaural Time Difference Tuning in the Barn Owl

The interaural time difference (ITD) is the primary auditory cue used by the barn owl for localization in the horizontal direction. ITD is initially computed by circuits consisting of axonal delay lines from one of the cochlear nuclei and coincidence detector neurons in the nucleus laminaris (NL). NL projects directly to the anterior part of the dorsal lateral lemniscal nucleus (LLDa), and this area projects to the core of the central nucleus of the inferior colliculus (ICcc) in the midbrain. To show the selectivity of an NL neuron for ITD requires averaging of responses over several stimulus presentations for each ITD. In contrast, ICcc neurons detect their preferred ITD in a single burst of stimulus. We recorded extracellularly the responses of LLDa neurons to ITD in anesthetized barn owls and show that this ability is already present in LLDa, raising the possibility that ICcc inherits its noise reduction property from LLDa.

Modeling the precedence effect in inferior colliculus neurons using converging excitatory and inhibitory inputs

Responses of a population model of low‐frequency inferior colliculus (IC) neurons to a pair of broadband clicks were evaluated. IC inputs came from Hodgkin‐Huxley models of medial superior olive (MSO) and cochlear nucleus bushy cells driven by a stochastic auditory nerve model. Each IC cell received converging inputs that were excitatory from ipsilateral MSO and inhibitory from contralateral MSO. Convergence of multiple excitatory, ipsilateral MSO inputs with similar interaural time difference (ITD) tuning improved ITD sensitivity and reduced the influence of MSO onset responses caused by monaural, rather than binaural, coincidences. Inhibition that lasted over several milliseconds suppressed IC responses to the lagging click. The effect of the inhibition depended on the ITD tuning of the excitation and inhibition converging on a given IC neuron. With appropriate convergence, the IC population showed no response to the lagging click at short delays, and responded to the lagging click but did not encode its ITD at intermediate delays. Only at longer inter‐click delays did IC responses show sensitivity to the lagging click ITD, consistent with the perceptual phenomenon of the precedence effect. [Work supported by NSF and NIH].

Synaptic depression may underly ITD stimulus adaptation in the inferior colliculus

Event Abstract Back to Event Synaptic depression may underly ITD stimulus adaptation in the inferior colliculus Phillipp Hehrmann1*, Julia Maier2, Nicol Harper3, David McAlpine3 and Maneesh Sahani1 1 University College London, Gatsby Computational Neuroscience Unit, United Kingdom 2 Carl von Ossietzky Universität Oldenburg, Germany 3 University College London, United Kingdom Adaptation of sensory neurons to the statistics of their respectivestimulus domain has been observed across many sensory systems and stimulus modalities. Here, we investigate mechanisms of neuronal adaptation to statistical distributions of interaural time differences (ITDs), an important binaural cue for the azimuthal localisation of a sound source. We propose a simple model of midbrain ITD processing that captures the essential features of adaptation that were observed in the inferior colliculus (IC) of anaesthetised guinea pigs. A key feature of our model is synaptic depression at the synapses of statically ITD-tuned neurons in the medial superior olive (MSO) projecting to the IC. The depression and recovery time constants were chosen to match earlier data measuring the time course of IC rate responses to pure tone stimuli with interaural phase differences (IPD) that switched between the best and worst IPD of a neuron. Our model replicates characteristic gain changes and shifts of both ITD tuning curves and Fisher Information curves in the IC when the mean of the stimulus distribution is changed. Also in agreement with experimental data, the model is insensitive to changes in stimulus variance. Hence, we propose that synaptic depression provides a simple candidate mechanism for the observed adaptive effects. Conference: Bernstein Symposium 2008, Munich, Germany, 8 Oct - 10 Oct, 2008. Presentation Type: Poster Presentation Topic: All Abstracts Citation: Hehrmann P, Maier J, Harper N, McAlpine D and Sahani M (2008). Synaptic depression may underly ITD stimulus adaptation in the inferior colliculus. Front. Comput. Neurosci. Conference Abstract: Bernstein Symposium 2008. doi: 10.3389/conf.neuro.10.2008.01.059 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Nov 2008; Published Online: 16 Nov 2008. * Correspondence: Phillipp Hehrmann, University College London, Gatsby Computational Neuroscience Unit, London, United Kingdom, phehrmann@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Phillipp Hehrmann Julia Maier Nicol Harper David McAlpine Maneesh Sahani Google Phillipp Hehrmann Julia Maier Nicol Harper David McAlpine Maneesh Sahani Google Scholar Phillipp Hehrmann Julia Maier Nicol Harper David McAlpine Maneesh Sahani PubMed Phillipp Hehrmann Julia Maier Nicol Harper David McAlpine Maneesh Sahani Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Sensitivity to Interaural Time Differences in the Inferior Colliculus with Bilateral Cochlear Implants

Bilateral cochlear implantation attempts to increase performance over a monaural prosthesis by harnessing the binaural processing of the auditory system. Although many bilaterally implanted human subjects discriminate interaural time differences (ITDs), a major cue for sound localization and signal detection in noise, their performance is typically poorer than that of normal-hearing listeners. We developed an animal model of bilateral cochlear implantation to study neural ITD sensitivity for trains of electric current pulses delivered via bilaterally implanted intracochlear electrodes. We found that a majority of single units in the inferior colliculus of acutely deafened, anesthetized cats are sensitive to ITD and that electric ITD tuning is as sharp as found for acoustic stimulation with broadband noise in normal-hearing animals. However, the sharpness and shape of ITD tuning often depended strongly on stimulus intensity; some neurons had dynamic ranges of ITD sensitivity as low as 1 dB. We also found that neural ITD sensitivity was best at pulse rates below 100 Hz and decreased with increasing pulse rate. This rate limitation parallels behavioral ITD discrimination in bilaterally implanted individuals. The sharp neural ITD sensitivity found with electric stimulation at the appropriate intensity is encouraging for the prospect of restoring the functional benefits of binaural hearing in bilaterally implanted human subjects and suggests that neural plasticity resulting from previous deafness and deprivation of binaural experience may play a role in the poor ITD discrimination with current bilateral implants.

Changes in interaural time sensitivity with interaural level differences in the inferior colliculus

We measured interaural time difference (ITD) sensitivity of 72 cells in the inferior colliculus of the anaesthetised guinea pig as a function of frequency and interaural level difference (ILD). For many units there was a “null” frequency, where varying the ILD made no difference to the position of the peak of the ITD sensitivity. This null frequency was not necessarily at the characteristic frequency (CF): it occurred at CF in less than a third of the neurons for which we had sufficient data (14/50). Equally often, the null occurred below (15/50) and less often, above CF (8/50). The remaining (13/50) neurons showed clear phase changes, but these were erratic or parallel and no null could be attributed. In 33 of the 37 neurons with an identifiable null frequency, the peak ITD moved towards the recording side with increasing ILD, for frequencies above the null, and away for frequencies below the null. The changes in ITD sensitivity expressed as phase were maximally about 0.2–0.3 cycles. Many of the changes in response phase with ILD are in the same direction and magnitude as changes in the phase locking with sound level in auditory nerve fibres. Thus, these changes in phase sensitivity at the basilar membrane and auditory nerve are maintained through to ITD tuning in the IC. This is consistent with a coincidence detection mechanism. However, some of the more complex phenomena which we observe are consistent with convergence at the IC.

Noise Reduction of Coincidence Detector Output by the Inferior Colliculus of the Barn Owl

A recurring theme in theoretical work is that integration over populations of similarly tuned neurons can reduce neural noise. However, there are relatively few demonstrations of an explicit noise reduction mechanism in a neural network. Here we demonstrate that the brainstem of the barn owl includes a stage of processing apparently devoted to increasing the signal-to-noise ratio in the encoding of the interaural time difference (ITD), one of two primary binaural cues used to compute the position of a sound source in space. In the barn owl, the ITD is processed in a dedicated neural pathway that terminates at the core of the inferior colliculus (ICcc). The actual locus of the computation of the ITD is before ICcc in the nucleus laminaris (NL), and ICcc receives no inputs carrying information that did not originate in NL. Unlike in NL, the rate-ITD functions of ICcc neurons require as little as a single stimulus presentation per ITD to show coherent ITD tuning. ICcc neurons also displayed a greater dynamic range with a maximal difference in ITD response rates approximately double that seen in NL. These results indicate that ICcc neurons perform a computation functionally analogous to averaging across a population of similarly tuned NL neurons.

Sensitivity to Interaural Time Differences in the Dorsal Nucleus of the Lateral Lemniscus of the Unanesthetized Rabbit: Comparison With Other Structures

Interaural time differences, a cue for azimuthal sound location, are first encoded in the superior olivary complex (SOC), and this information is then conveyed to the dorsal nucleus of the lateral lemniscus (DNLL) and inferior colliculus (IC). The DNLL provides a strong inhibitory input to the IC and may serve to transform the coding of interaural time differences (ITDs) in the IC. Consistent with the projections from the SOC, the DNLL and IC had similar distributions of peak- and trough-type neurons, characteristic delays, and best ITDs. The ITD tuning widths of DNLL neurons were intermediate between those of the SOC and IC. Further sharpening is seen in the auditory thalamus, indicating that sharpening mechanisms are not restricted to the midbrain. The proportion of neurons that phase-locked to the tones delivered to each ear progressively decreased from the SOC to the auditory thalamus. The degree of phase-locking for a large majority of DNLL neurons was too weak to support their involvement in processing monaural inputs to generate a sensitivity to ITDs. The response rates of DNLL neurons were on average approximately 60% greater than in the IC or SOC, indicating that the inhibitory input provided to the IC by the DNLL is robust.

GABAergic Inhibition Controls Neural Gain in Inferior Colliculus Neurons Sensitive to Interaural Time Differences

We investigated the role of GABAergic inhibition on the responses of inferior colliculus (IC) neurons sensitive to interaural time differences (ITDs) in anesthetized guinea pigs. Responses to static and dynamic ITDs were obtained before, during, and after recovery from ionotophoretic application of GABA, or antagonists to the GABA(A) receptor gabazine and bicuculline. For most neurons, a linear relationship was observed between discharge rates evoked by a particular ITD during drug application and control discharge rates. Blocking GABAergic inhibition, or adding exogenous GABA, scaled IC discharge rates in a multiplicative (divisive) and/or additive (subtractive) manner. When the influence of iontophoresed GABA antagonists or exogenous GABA on discharge rates was accounted for, GABAergic inhibition was found to have no effect on the ITD tuning properties of IC neurons. The tuning sharpness of ITD functions, the ITD that evoked 50% response magnitude, and the relative symmetry of ITD functions around their peak response were unaffected by blockade of inhibition or addition of tonic inhibition. However, the ability of neurons to discriminate between ITDs by virtue of differences in their discharge rate was altered by blocking or adding GABA. We propose that inhibition in the IC is involved in the control of the neural gain of the output of IC neurons rather than the regulation of ITD tuning. This gain control appears to arise from a combination of additive and multiplicative processes, and may involve mechanisms such as shunting inhibition or changes in the efficacy of inhibitory and excitatory inputs.

Development of Sound Localization Mechanisms in the Mongolian Gerbil Is Shaped by Early Acoustic Experience

Sound localization is one of the most important tasks performed by the auditory system. Differences in the arrival time of sound at the two ears are the main cue to localize low-frequency sound in the azimuth. In the mammalian brain, such interaural time differences (ITDs) are encoded in the auditory brain stem; first by the medial superior olive (MSO) and then transferred to higher centers, such as the dorsal nucleus of the lateral lemniscus (DNLL), a brain stem nucleus that gets a direct input from the MSO. Here we demonstrate for the first time that ITD sensitivity in gerbils undergoes a developmental maturation after hearing onset. We further show that this development can be disrupted by altering the animal's acoustic experience during a critical period. In animals that had been exposed to omnidirectional white noise during a restricted time period right after hearing onset, ITD tuning did not develop normally. Instead, it was similar to that of juvenile animals 3 days after hearing onset, with the ITD functions not adjusted to the physiological range. Animals that had been exposed to omnidirectional noise as adults did not show equivalent abnormal ITD tuning. The development presented here is in contrast to that of the development of neuronal representation of ITDs in the midbrain of barn owls and interaural intensity differences in ferrets, where the representations are adjusted by an interaction of auditory and visual inputs. The development of ITD tuning presented here most likely depends on normal acoustic experience and may be related to the maturation of inhibitory inputs to the ITD detector itself.

Role of GABAergic Inhibition in the Coding of Interaural Time Differences of Low-Frequency Sounds in the Inferior Colliculus

A major cue for the localization of sound in space is the interaural time difference (ITD). We examined the role of inhibition in the shaping of ITD responses in the inferior colliculus (IC) by iontophoretically ejecting gamma-aminobutyric acid (GABA) antagonists and GABA itself using a multibarrel pipette. The GABA antagonists block inhibition, whereas the applied GABA provides a constant level of inhibition. The effects on ITD responses were evaluated before, during and after the application of the drugs. If GABA-mediated inhibition is involved in shaping ITD tuning in IC neurons, then applying additional amounts of this inhibitory transmitter should alter ITD tuning. Indeed, for almost all neurons tested, applying GABA reduced the firing rate and consequently sharpened ITD tuning. Conversely, blocking GABA-mediated inhibition increased the activity of IC neurons, often reduced the signal-to-noise ratio and often broadened ITD tuning. Blocking GABA could also alter the shape of the ITD function and shift its peak suggesting that the role of inhibition is multifaceted. These effects indicate that GABAergic inhibition at the level of the IC is important for ITD coding.

A physiologically based model of interaural time difference discrimination.

Interaural time difference (ITD) is a cue to the location of sounds containing low frequencies and is represented in the inferior colliculus (IC) by cells that respond maximally at a particular best delay (BD). Previous studies have demonstrated that single ITD-sensitive cells contain sufficient information in their discharge patterns to account for ITD acuity on the midline (ITD = 0). If ITD discrimination were based on the activity of the most sensitive cell available ("lower envelope hypothesis"), then ITD acuity should be relatively constant as a function of ITD. In response to broadband noise, however, the ITD acuity of human listeners degrades as ITD increases. To account for these results, we hypothesize that pooling of information across neurons is an essential component of ITD discrimination. This report describes a neural pooling model of ITD discrimination based on the response properties of ITD-sensitive cells in the IC of anesthetized cats. Rate versus ITD curves were fit with a cross-correlation model of ITD sensitivity, and the parameters were used to constrain a population model of ITD discrimination. The model accurately predicts ITD acuity as a function of ITD for broadband noise stimuli when responses are pooled across best frequency (BF). Furthermore, ITD tuning based solely on a system of internal delays is not sufficient to predict ITD acuity in response to 500 Hz tones, suggesting that acuity is likely refined by additional mechanisms. The physiological data confirms evidence from the guinea pig that BD varies systematically with BF, generalizing the observation across species.

Subthreshold outward currents enhance temporal integration in auditory neurons.

Many auditory neurons possess low-threshold potassium currents ( I(KLT)) that enhance their responsiveness to rapid and coincident inputs. We present recordings from gerbil medial superior olivary (MSO) neurons in vitro and modeling results that illustrate how I(KLT) improves the detection of brief signals, of weak signals in noise, and of the coincidence of signals (as needed for sound localization). We quantify the enhancing effect of I(KLT) on temporal processing with several measures: signal-to-noise ratio (SNR), reverse correlation or spike-triggered averaging of input currents, and interaural time difference (ITD) tuning curves. To characterize how I(KLT), which activates below spike threshold, influences a neuron's voltage rise toward threshold, i.e., how it filters the inputs, we focus first on the response to weak and noisy signals. Cells and models were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the "noise"), together with a larger but still subthreshold postsynaptic conductance, EPSG (the "signal"). Reduction of I(KLT) decreased the SNR, mainly due to an increase in spontaneous firing (more "false positive"). The spike-triggered reverse correlation indicated that I(KLT) shortened the integration time for spike generation. I(KLT) also heightened the model's timing selectivity for coincidence detection of simulated binaural inputs. Further, ITD tuning is shifted in favor of a slope code rather than a place code by precise and rapid inhibition onto MSO cells (Brand et al. 2002). In several ways, low-threshold outward currents are seen to shape integration of weak and strong signals in auditory neurons.