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Developmental Determination of Central Auditory Physiology by the Inner Ear

内耳中枢听觉生理学的发育决定

基本信息

批准号：
10365728
负责人：
R. Michael Burger
金额：
$ 36.73万
依托单位：
LEHIGH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10365728
关键词：
Ablation Acoustic Nerve Address Anatomy Animals Apoptotic Architecture Auditory Auditory Physiology Auditory system Basilar Papilla Biophysics Birds Brain Brain Stem Brain region Cell Nucleus Characteristics Chick Cochlea Cochlear nucleus Cues Data Dependence Development Ear Early Intervention Electrophysiology (science)Embryo Epithelial Exhibits Failure Frequencies Genetic Goals Hair Cells Health Hearing Hearing problem Human Instruction Intervention Investigation Ion Channel Knowledge Labyrinth Mammals Maps Methods Mission Modeling Molecular Morphology National Institute on Deafness and Other Communication Disorders Neuraxis Neurons Pathway interactions Pattern Peripheral Phenotype Physiology Population Process Property Research Role Sensory Signal Transduction Source Structure Synapses System Testing Therapeutic Therapeutic Intervention Time Work base bone morphogenic protein childhood hearing loss chordin cochlear development critical period deaf deafening deafness experimental study genetic manipulation hearing impairment hearing preservation innovation insight juvenile animal morphogens nerve supply neural patterning neurodevelopment neuron loss otoconia overexpression preservation relating to nervous system response sound tool

项目摘要

Project Summary: A longstanding and fundamental question of neural development in sensory pathways is: What is the role of the organization of the sensory epithelium in establishing central topographic organization? In the auditory system a direct approach to addressing this question has been elusive because it has not been possible to manipulate the input to the brain from the auditory periphery without either complete ablation of the inner ear or induction of hearing dysfunction. The proposed experiments will establish for the first time, a model of repatterned frequency representation in the chick inner ear by utilizing a new genetic manipulation in embryos. This manipulation takes advantage of the known genetic factors that establish the organization of the ear at a very early developmental stage that precedes the auditory nerve innervation of the central nervous system. By overexpressing one of these factors, bone morphogenic protein 7 (BMP7), inner ears develop almost exclusively low frequency hair cell phenotypes. In the first brain structure to receive auditory nerve input, the cochlear nucleus, neurons express a number of well characterized biophysical and morphological specializations for processing sound in specific frequencies. Frequency specific tuning is topographically mapped in both the ear and auditory brain regions, a feature known as 'tonotopy.' Thus, neural specialization occurs along an orderly tonotopic map in the cochlear nucleus. The central hypothesis of this proposal is that tonotopic refinement of specializations in the cochlear nucleus is developmentally determined by patterned input from the inner ear, and is not independently induced by local cues in the developing brain. This hypothesis is now testable using animals with tonotopically altered inner ears. The first aim of this proposal is to examine whether the BMP7 manipulation indeed induces repatterning of hair cell tuning mechanism in the inner ear. The second aim investigates the electrical input response properties of cochlear nucleus neurons in animals that have developed with tonotopically altered inner ears. Finally, the third aim will investigate the dependence of cochlear nucleus structure on normal topographic innervation from the auditory nerve. These research objectives, if successful, will provide new insights into the mechanisms that establish the functional organization of auditory structures. Revelation of these mechanisms may be informative to optimization strategies for therapeutic interventions in early deafness or hearing loss that aim to preserve normal function and capacity in auditory circuitry.

项目总结: