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.
