Hearing impairment is one of the most common sensory abnormalities in humans, affecting nearly 30 million people in the United States. Hearing impairments are caused by several pathogenic processes including structural and genetic defects, infections, environmental exposures and trauma. Pathogenic effects on the peripheral auditory system (ear, cochlea, and auditory nerve) are well-described, and several animal models have been created to study them. However, a dearth of animal models to study normal and disrupted embryogenesis of the central auditory system has led to an incomplete understanding of developmental processes that control central auditory neuron specification, differentiation, axonal targeting, and trophic interactions. This, in turn, has limited our understanding of pathophysiological mechanisms and their consequences on the central auditory system. The overall goal of this proposal is to understand how disruptions of brain morphogenesis affect central auditory system development, connectivity and function. We have developed new mouse models that will, for the first time, allow us to study these processes as they relate to inferior colliculus (IC) and superior olivary complex (SOC) neurons. We expect that insights gained from these models will inform us as to how disruptions of auditory neuron development can contribute to human hearing disorders.

Public Health Relevance

Hearing impairment is one of the most common sensory abnormalities in humans, affecting ~16.1% of the US population. This project addresses how developmental disruption of the central auditory system affects its overall organization, connectivity and function. Understanding the role of different components of the central auditory system will provide insight into how their loss of can cause hearing impairment and help in developing therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DC011982-03
Application #
8515989
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2011-08-15
Project End
2014-08-14
Budget Start
2013-08-15
Budget End
2014-08-14
Support Year
3
Fiscal Year
2013
Total Cost
$62,030
Indirect Cost
Name
Case Western Reserve University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Altieri, Stefanie C; Zhao, Tianna; Jalabi, Walid et al. (2014) Development of glycinergic innervation to the murine LSO and SPN in the presence and absence of the MNTB. Front Neural Circuits 8:109
Jalabi, Walid; Kopp-Scheinpflug, Cornelia; Allen, Paul D et al. (2013) Sound localization ability and glycinergic innervation of the superior olivary complex persist after genetic deletion of the medial nucleus of the trapezoid body. J Neurosci 33:15044-9