权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Peripheral vestibular hypofunction and neurosensory coding

周围前庭功能减退和神经感觉编码

基本信息

批准号：
10186081
负责人：
LARRY F HOFFMAN
金额：
$ 64.21万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10186081
关键词：
Address Afferent Neurons Ally Animal Model Animals Antibodies Apical Architecture Autoimmune Behavior Behavior Therapy Behavioral Bilateral Characteristics Code Contralateral Crista ampullaris Development Docking Dose Electrophysiology (science)Epithelial Exhibits Foundations Frequencies Functional disorder General Population Gentamicins Hair Cells Histologic Immunohistochemistry Investigation Ipsilateral Label Laboratories Labyrinth Lesion Lighting Measures Meta-Analysis Microscopy Morphology Na(+)-K(+)-Exchanging ATPase Neurobiology OTOF gene Outcome Pathologic Patients Peripheral Phase Phenotype Physiological Prevalence Production Recovery Reproducibility Research Resolution Response to stimulus physiology Salvelinus Scanning Sensory Shapes Specimen Stimulus Structure Synapses Synaptic Cleft Testing Time Transmission Electron Microscopy Tubulin Type I Hair Cell Utricle structure Vestibular Function Tests Vestibular Neuronitis Work base behavior test calyx structure insight light microscopy neurosensory ototoxin postsynaptic presynaptic public health relevance rehabilitation strategy relating to nervous system response ribbon synapse uptake vestibulo-ocular reflex

项目摘要

Project Summary The proposed research addresses critical issues of high translational importance concerning the mechanisms and outcomes of partial dysfunction of the vestibular sensory epithelia, referred to as peripheral vestibular hypofunction. The research plan utilizes chemotoxin- induced hypofunction, the foundation for which was identified through recent work from the PI’s laboratory in an animal model enabling precise intraperilymphatic dosing resulting in the production of highly reproducible lesions. This provides the basis for producing lesions of graded magnitudes within the sensory neuroepithelia, documented through histopathologic analyses. The physiologic outcome of these lesions will be evaluated through recordings of single afferent neuron electrophysiology and the vestibulo-ocular reflex, providing the bases for establishing histologic and physiologic correlates to a direct behavioral test of vestibular function. Previous work has demonstrated that the afferent neuron calyx is highly labile to pathologic compromise, and owing to its important contribution to shaping neural dynamics in untreated epithelia it is a focus for assessing pathologic damage. The present research plan will enable the direct correlate of afferent discharge dynamics to critical cellular components of the calyx, including its morphology and expression of KCNQ4 and sodium-potassium ATPase. In addition, we will examine the distribution of synaptic ribbons within hair cells of lesioned epithelia, testing whether a systematic synaptopathy also contributes to the compromised vestibular function. In summary, the present investigation provides critical insight into the histopathologic substrates of vestibular hypofunction and the alterations in sensory coding that underlies the functional compromise. At the same time, however, this investigation will reveal important cellular and physiologic metrics that are required for normal vestibular function, addressing longstanding question in vestibular neurobiology.

项目总结