Mechanisms Regulating Synaptic Function in the Developing Auditory System

Project: Research project

Project Details

Description

The goal of this research is to identify mechanisms that give rise to ultrafast and temporally precise auditory information processing in the brainstem, where such properties are fundamental for the encoding of behaviorally relevant communication signals. Fast synaptic transmission mediated by AMPA-type glutamate receptors play a critical role in the ability to precisely encode the timing of acoustic information. Currently, the developmental mechanisms that regulate their fast synaptic properties are not completely understood. The proposed research will address this by identifying the molecular-level mechanisms that regulate synaptic function in the developing auditory system.

It is well know that among non-auditory regions in the brain, the developmental regulation of synaptic AMPA receptor properties is dependent on activation of another glutamate-type receptor, the NMDA receptor. Despite the prevalence of NMDA receptors in the auditory system, their role during development is not known. The specific aims of this research proposal are designed to test the hypothesis that NMDA receptors regulate synaptic AMPA receptor properties during auditory system development.

Using an innovative approach to eliminate the genetic expression of NMDA receptors, the project aims to determine the time course of functional changes in AMPA receptor number and subunit composition among cochlear nucleus magnocellularis neurons in the chicken auditory brainstem. The effects of genetic manipulation on synaptic AMPA receptor number and composition will be investigated using electrophysiology approaches at multiple developmental time periods that correspond to synapse formation, hearing onset and functional maturation.

The experiments proposed for the current research project are significant for several reasons. First, the prevalence of glutamate receptors throughout the brain, and their important roles in development, neurotransmission and excitotoxicity, has implicated them as a primary target underlying pathologies of many brain disorders. Second, a better appreciation of how glutamate receptors contribute to synaptic assembly, development, and refinement – to the subsequent maturation of neural circuits – may shed light on normal auditory function. Finally, an in depth understanding of these molecular-level mechanisms may potentially provide pharmacological targets to improve disorders in which synaptic dysfunction has either a direct or causal role in pathologies of the auditory system.
StatusFinished
Effective start/end date7/1/156/30/19

Funding

  • National Institute on Deafness and Other Communication Disorders (5R03DC013841-02)

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