Cellular Mechanisms of Binaural Hearing Neurons in an Avian Interaural Level Difference Circuit

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Project Summary Humans and animals rely on sound localization to communicate and survive in complex acoustic environments. The auditory periphery (cochlea), however, does not encode the location of sound. Instead, the central auditory system computes horizontal sound location by encoding binaural cues such as interaural time and level difference (ITD and ILD). Despite the valuable insight that comparative work of ITD coding between mammals and birds has produced for understanding human auditory processing, there is a gap in knowledge for the cellular mechanisms of ILD coding in birds, limiting our understanding of the range of possible coding strategies and circuitry development for sound localization. Because sound localization ability is diminished in humans with hearing impairments and those with cochlear implants, identifying new mechanisms for ILD coding may inspire new technologies and approaches to restore sound localization ability. Avian models have been essential for developing the principles of sound localization coding and have produced a strong framework for understanding human auditory processing. In birds, the first central auditory nucleus encoding ILD is the posterior portion of the dorsal nucleus of the lateral lemniscus (LLDp; formerly VLVp, nucleus ventralis lemnisci lateralis pars posterior). Previous in vivo and histological studies have shown that LLDp neurons receive excitatory inputs from the contralateral cochlear nucleus, as well as inhibitory inputs from the other LLD. However, little is known about the specialized physiological and morphological properties of LLDp neurons that enable them to encode ILD. To determine the cellular mechanisms underlying ILD coding in the avian ILD circuitry, in vitro slice electrophysiology will be used to record from individual neurons in the chicken LLDp. The proposed work will test three hypothetical models to determine whether the LLDp encodes ILD through the use of (A) interneurons, (B) one principal cell population, or (C) two principal cell populations, and determine the specializations needed to support the circuit. Aim 1 will determine the intrinsic neuronal properties of LLDp neurons, such as action potential firing patterns will establish the criteria for identifying cell types for the next two aims. Aim 2 will characterize the synaptic properties of excitatory and inhibitory transmission in the LLDp and establish a working cellular model for ILD coding in birds. Aim 3 will identify individual cell morphology, neurotransmitter utilization, and projections between the two LLDs to determine how the anatomy of the LLDp relates to its physiology. The results are expected to establish a working cellular model for avian ILD coding, provide foundational interpretations for avian in vivo physiological and behavioral research, and advance our understanding of the cellular mechanisms underlying synaptic inhibition in auditory processing.