# Cellular properties mediating specialization of lateral superior olive principal neuron types for timing and intensity based sound localization

> **NIH NIH R21** · NORTHEAST OHIO MEDICAL UNIVERSITY · 2021 · $156,000

## Abstract

Project abstract
Principal neurons (PNs) of the lateral superior olive (LSO) in the brainstem of mammals are a key component in
the processing of binaural cues used for sound localization that underlie selective attention. They accomplish this
by comparing excitatory synaptic inputs driven by the ipsilateral ear with inhibitory inputs driven by the
contralateral ear. It is increasingly appreciated that along with their classical role of interaural intensity difference
(IID) coding, LSO PNs also encode interaural time differences (ITDs). These two functional roles, along with the
tonotopic organization of the LSO, place different demands on the cellular properties of LSO neurons. My major
hypothesis is that there is functional segregation of LSO PNs for IID and ITD coding. This functional segregation
may be defined by transmitter released, projection pattern, morphology, dendritic integration functions, or
synaptic inputs. This proposal will develop core methodologies to access these cellular features of the LSO.
Excitatory LSO PNs are biased to higher frequency regions and largely project contralaterally while inhibitory
cells are biased to lower frequencies and project Ipsilaterally. Firing response characteristics associated with
phase locking and ITD coding are biased toward lower frequency regions, potentially associating with inhibitory
PNs. I will investigate the possibility that ipsilateral projecting inhibitory PNs are better adapted for ITD coding
while contralateral projecting excitatory PNs are better adapted for IID coding. This potentially provides a means
to segregate this information in upstream centers. Critical for understanding whether inhibitory and excitatory
cells have distinct functional roles within the circuit is their relative intrinsic cellular properties. To efficiently
investigate this I will develop a transgenic mouse line that will allow me to target excitatory and inhibitory cell
types during brain slice physiology experiments. My expectation is that inhibitory/ITD coding cells would have
lower input resistances, faster membrane time constants, larger diameter and less complicated dendrites, and
phasic firing type, whereas, excitatory/IID coding will be associated with more integrative membrane properties.
These experiments will yield foundational insights into the cellular organization of the LSO. Efficacy of
propagation of action potentials and synaptic potentials in dendrites is a critical component of integrative
functions and synaptic plasticity in neurons which cannot be measured from somatic recordings alone. Recent
work has revealed dendritic properties that have adapted for ITD coding. In contrast, almost nothing is known of
the electrical properties of LSO dendrites or what aspects of dendritic physiology best support IID coding. I will
develop methodologies using multiphoton imaging to make unbiased dual dendritic/somatic patch recordings
from LSO neurons which allow for the analysis not only of local res...

## Key facts

- **NIH application ID:** 10147029
- **Project number:** 5R21DC017819-03
- **Recipient organization:** NORTHEAST OHIO MEDICAL UNIVERSITY
- **Principal Investigator:** Bradley D Winters
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $156,000
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147029

## Citation

> US National Institutes of Health, RePORTER application 10147029, Cellular properties mediating specialization of lateral superior olive principal neuron types for timing and intensity based sound localization (5R21DC017819-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147029. Licensed CC0.

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