Functional Refinement in the Projection from Ventral Cochlear Nucleus to Lateral Superior Olive Precedes Hearing Onset in Rat

Principal neurons of the lateral superior olive (LSO) compute the interaural intensity differences necessary for localizing high-frequency sounds. To perform this computation, the LSO requires precisely tuned, converging excitatory and inhibitory inputs that are driven by the two ears and that are matched for stimulus frequency. In rodents, the inhibitory inputs, which arise from the medial nucleus of the trapezoid body (MNTB), undergo extensive functional refinement during the first postnatal week. Similar functional refinement of the ascending excitatory pathway, which arises in the anteroventral cochlear nucleus (AVCN), has been assumed but has not been well studied. Using whole-cell voltage clamp in acute brainstem slices of neonatal rats, we examined developmental changes in input strength and pre- and post-synaptic properties of the VCN-LSO pathway. A key question was whether functional refinement in one of the two major input pathways might precede and then guide refinement in the opposite pathway. We find that elimination and strengthening of VCN inputs to the LSO occurs over a similar period to that seen for the ascending inhibitory (MNTB-LSO) pathway. During this period, the fractional contribution provided by NMDA receptors (NMDARs) declines while the contribution from AMPA receptors (AMPARs) increases. In the NMDAR-mediated response, GluN2B-containing NMDARs predominate in the first postnatal week and decline sharply thereafter. Finally, the progressive decrease in paired-pulse depression between birth and hearing onset allows these synapses to follow progressively higher frequencies. Our data are consistent with a model in which the excitatory and inhibitory projections to LSO are functionally refined in parallel during the first postnatal week, and they further suggest that GluN2B-containing NMDARs may mediate early refinement in the VCN-LSO pathway

Linear coding of complex sound spectra by discharge rate by neurons of the medial nucleus of the trapezoidal body (MNTB) and thier inputs

The interaural level difference (ILD) cue to sound location is first encoded in the lateral superior olive (LSO). ILD sensitivity results because the LSO receives excitatory input from the ipsilateral cochlear nucleus and inhibitory input indirectly from the contralateral cochlear nucleus via glycinergic neurons of the ipsilateral medial nucleus of the trapezoid body (MNTB). It is hypothesized that in order for LSO neurons to encode ILDs, the sound spectra at both ears must be accurately encoded via spike rate by their afferents. This spectral-coding hypothesis has not been directly tested in MNTB, likely because MNTB neurons have been mostly described and studied recently in regards to their abilities to encode temporal aspects of sounds, not spectral. Here, we test the hypothesis that MNTB neurons and their inputs from the cochlear nucleus and auditory nerve code sound spectra via discharge rate. The Random Spectral Shape method was used to estimate how the levels of 100-ms duration spectrally stationary stimuli were weighted, both linearly and non- linearly, across a wide band of frequencies. In general, MNTB neurons and their globular bushy cell inputs, were found to be well-modeled by a linear weighting of spectra demonstrating that the pathways through the MNTB can accurately encode sound spectra including those resulting from the acoustical cues to sound location provided by head-related directional transfer functions. Together with the anatomical and biophysical specializations for timing in the MNTB-LSO complex, these mechanisms may allow ILDs to be computed for complex stimuli with rapid spectrotemporally-modulated envelopes such as speech and animal vocalizations and moving sound sources

Effects of interaural decoherence on sensitivity to interaural level differences across frequency

The interaural level difference (ILD) is a robust indicator of sound source azimuth, and human ILD sensitivity persists under conditions that degrade normally-dominant interaural time difference (ITD) cues. Nonetheless, ILD sensitivity varies somewhat with both stimulus frequency and interaural correlation (coherence). To further investigate the combined binaural perceptual influence of these variables, the present study assessed ILD sensitivity at frequencies 250-4000 Hz using stimuli of varied interaural correlation. In the first of two experiments, ILD discrimination thresholds were modestly elevated, and subjective lateralization slightly reduced, for both half-correlated and uncorrelated narrowband noise tokens relative to correlated tokens. Different from thresholds in the correlated condition, which were worst at 1000 Hz [Grantham, D.W. (1984). J. Acoust. Soc. Am. 75, 1191-1194], thresholds in the decorrelated conditions were independent of frequency. However, intrinsic envelope fluctuations in narrowband stimuli caused moment-to-moment variation of the nominal ILD, complicating interpretation of measured thresholds. Thus, a second experiment employed low-fluctuation noise tokens, revealing a clear effect of interaural decoherence per se that was strongly frequency-dependent, decreasing in magnitude from low to high frequencies. Measurements are consistent with known integration times in ILD-sensitive neurons and also suggest persistent influences of covert ITD cues in putative "ILD" tasks

Roles for Coincidence Detection in Coding Amplitude-Modulated Sounds.

Many sensory neurons encode temporal information by detecting coincident arrivals of synaptic inputs. In the mammalian auditory brainstem, binaural neurons of the medial superior olive (MSO) are known to act as coincidence detectors, whereas in the lateral superior olive (LSO) roles of coincidence detection have remained unclear. LSO neurons receive excitatory and inhibitory inputs driven by ipsilateral and contralateral acoustic stimuli, respectively, and vary their output spike rates according to interaural level differences. In addition, LSO neurons are also sensitive to binaural phase differences of low-frequency tones and envelopes of amplitude-modulated (AM) sounds. Previous physiological recordings in vivo found considerable variations in monaural AM-tuning across neurons. To investigate the underlying mechanisms of the observed temporal tuning properties of LSO and their sources of variability, we used a simple coincidence counting model and examined how specific parameters of coincidence detection affect monaural and binaural AM coding. Spike rates and phase-locking of evoked excitatory and spontaneous inhibitory inputs had only minor effects on LSO output to monaural AM inputs. In contrast, the coincidence threshold of the model neuron affected both the overall spike rates and the half-peak positions of the AM-tuning curve, whereas the width of the coincidence window merely influenced the output spike rates. The duration of the refractory period affected only the low-frequency portion of the monaural AM-tuning curve. Unlike monaural AM coding, temporal factors, such as the coincidence window and the effective duration of inhibition, played a major role in determining the trough positions of simulated binaural phase-response curves. In addition, empirically-observed level-dependence of binaural phase-coding was reproduced in the framework of our minimalistic coincidence counting model. These modeling results suggest that coincidence detection of excitatory and inhibitory synaptic inputs is essential for LSO neurons to encode both monaural and binaural AM sounds

Physiological models of the lateral superior olive.

In computational biology, modeling is a fundamental tool for formulating, analyzing and predicting complex phenomena. Most neuron models, however, are designed to reproduce certain small sets of empirical data. Hence their outcome is usually not compatible or comparable with other models or datasets, making it unclear how widely applicable such models are. In this study, we investigate these aspects of modeling, namely credibility and generalizability, with a specific focus on auditory neurons involved in the localization of sound sources. The primary cues for binaural sound localization are comprised of interaural time and level differences (ITD/ILD), which are the timing and intensity differences of the sound waves arriving at the two ears. The lateral superior olive (LSO) in the auditory brainstem is one of the locations where such acoustic information is first computed. An LSO neuron receives temporally structured excitatory and inhibitory synaptic inputs that are driven by ipsi- and contralateral sound stimuli, respectively, and changes its spike rate according to binaural acoustic differences. Here we examine seven contemporary models of LSO neurons with different levels of biophysical complexity, from predominantly functional ones ('shot-noise' models) to those with more detailed physiological components (variations of integrate-and-fire and Hodgkin-Huxley-type). These models, calibrated to reproduce known monaural and binaural characteristics of LSO, generate largely similar results to each other in simulating ITD and ILD coding. Our comparisons of physiological detail, computational efficiency, predictive performances, and further expandability of the models demonstrate (1) that the simplistic, functional LSO models are suitable for applications where low computational costs and mathematical transparency are needed, (2) that more complex models with detailed membrane potential dynamics are necessary for simulation studies where sub-neuronal nonlinear processes play important roles, and (3) that, for general purposes, intermediate models might be a reasonable compromise between simplicity and biological plausibility

The precedence effect in sound localization

In ordinary listening environments, acoustic signals reaching the ears directly from real sound sources are followed after a few milliseconds by early reflections arriving from nearby surfaces. Early reflections are spectrotemporally similar to their source signals but commonly carry spatial acoustic cues unrelated to the source location. Humans and many other animals, including nonmammalian and even invertebrate animals, are nonetheless able to effectively localize sound sources in such environments, even in the absence of disambiguating visual cues. Robust source localization despite concurrent or nearly concurrent spurious spatial acoustic information is commonly attributed to an assortment of perceptual phenomena collectively termed "the precedence effect," characterizing the perceptual dominance of spatial information carried by the first-arriving signal. Here, we highlight recent progress and changes in the understanding of the precedence effect and related phenomena

Effects of inhibition parameters on binaural phase coding.

<p><b>A-C:</b> Effects of the threshold increase δ. <b>D-F:</b> Effects of the inhibition window width Δ. <b>A,D:</b> Phase-tuning curves. <b>B,E:</b> Peak and trough rates of the phase tuning curves. <b>C,F:</b> Half-peak width and trough phase of the phase tuning curves.</p

Between-ear sound frequency disparity modulates a brain stem biomarker of binaural hearing

The auditory brain stem response (ABR) is an evoked potential that indexes a cascade of neural events elicited by sound. In the present study we evaluated the influence of sound frequency on a derived component of the ABR known as the binaural interaction component (BIC). Specifically, we evaluated the effect of acoustic interaural (between-ear) frequency mismatch on BIC amplitude. Goals were to 1) increase basic understanding of sound features that influence this long-studied auditory potential and 2) gain insight about the persistence of the BIC with interaural electrode mismatch in human users of bilateral cochlear implants, presently a limitation on the prospective utility of the BIC in audiological settings. Data were collected in an animal model that is audiometrically similar to humans, the chinchilla (Chinchilla lanigera; 6 females). Frequency disparities and amplitudes of acoustic stimuli were varied over broad ranges, and associated variation of BIC amplitude was quantified. Subsequently, responses were simulated with the use of established models of the brain stem pathway thought to underlie the BIC. Collectively, the data demonstrate that at high sound intensities (>= 85 dB SPL), the acoustically elicited BIC persisted with interaurally disparate stimulation (click frequencies >= 1.5 octaves apart). However, sharper tuning emerged at moderate sound intensities (65 dB SPL), with the largest BIC occurring for stimulus frequencies within similar to 0.8 octaves, equivalent to +/- 1 mm in cochlear place. Such responses were consistent with simulated responses of the presumed brain stem generator of the BIC, the lateral superior olive. The data suggest that leveraging focused electrical stimulation strategies could improve BIC-based bilateral cochlear implant fitting outcomes. NEW & NOTEWORTHY Traditional hearing tests evaluate each ear independently. Diagnosis and treatment of binaural hearing dysfunction remains a basic challenge for hearing clinicians. We demonstrate in an animal model that the prospective utility of a noninvasive electrophysiological signature of binaural function, the binaural interaction component (BIC), depends strongly on the intensity of auditory stimulation. Data suggest that more informative BIC measurements could be obtained with clinical protocols leveraging stimuli restricted in effective bandwidth