Cellular diversity in the superior olivary complex underlying timing- and intensity-based sound localization - Project abstract The superior olivary complex (SOC) in the brainstem of mammals integrates information from the two ears enabling sound localization. This ability underlies selective auditory attention and is disrupted by hearing loss and in children with central auditory processing disorder (CAPD). Principal neurons of lateral superior olive (LSO PNs) are critical for these functions. The classical view of the LSO is a homogeneous block of cells that extracts ongoing interaural level differences (ILDs), however, it is increasingly implicated in encoding interaural time differences (ITDs) for broadband transients and amplitude modulations. Cellular properties are fundamental to how neurons extract and encode information. ILD/ITD processing places disparate demands on neuronal properties and there is cellular diversity in the LSO that is not well-understood. It is also critical to understand how different types of information may be organized in higher processing centers such as the inferior colliculus (IC). Our overarching hypothesis is that LSO PN cellular diversity supports both ILD and ITD coding and neurotransmitter system, intrinsic excitability, and projection pattern provide means to organize differentially extracted information in the IC. We found that LSO PNs consist of inhibitory and excitatory cell types with different projection patterns, intrinsic membrane properties, and morphology. Aim 1 will begin to address what produces these differences, how they relate to ILD/ITD extraction, and how conductive hearing loss (CHL) affects them using the mouse model. To do this we will compare LSO PN types at the level of gene expression using PatchSeq and electrophysiologically using computational modelling, ex vivo patch-clamp, and in vivo intracellular technique. Aim 2 will further probe the functional implications of our preliminary findings by examining the synaptic drive onto these cells with the goal of finding input-output relationships that support different sound localization coding strategies. These data and Aim 1 findings will be used to update computational models of LSO neurons used to test ILD/ITD functions. We will also use bilateral electrical synaptic stimulation to examine how cell types transform inputs. Signal propagation in dendrites is a critical parameter of integrative functions. Very little is known about dendritic processing in LSO neurons. Aim 3 will begin to address this gap in our knowledge and help us understand what dendritic properties facilitate diverse ILD/ITD coding strategies using dual somatic- dendritic recordings and two-photon calcium imaging. These aims are conceptually innovative in their treatment of the LSO as a diverse group with cellular properties tuned for multiple functional roles and methodologically innovative in our use of transcriptomics and computational models to target ex vivo and in vivo electrophysiological studies. This project will yield foundational insights into the cellular organization of the SOC which may be disrupted by hearing loss and contribute to poorly understood disease states such as CAPD.
