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Developmental Contributions to the Functional Maturation of the Vestibulo-Ocular Reflex

前庭眼反射功能成熟的发育贡献

基本信息

批准号：
10679875
负责人：
Paige Leary
金额：
$ 4.44万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10679875
关键词：
Ablation Address Anatomy Animal Behavior Animals Automobile Driving Behavior Biological Assay Birth Birth Order Brain Brain Stem Childhood Data Date of birth Development Developmental Process Disease Ear Event Eye Movements Functional disorder Genetic Goals Head Health Human Image Impaired health Knowledge Lesion Link Location Measures Mission Modeling Motor Neurons Movement Neurodevelopmental Disorder Neurons Neurosciences Nose Optics Play Population Population Heterogeneity Property Protocols documentation Public Health Research Role Sensory Shapes System Technology Testing Time United States National Institutes of Health Work Zebrafish assay development associated symptom developmental disease disabling symptom experimental study gain of function gaze improved loss of function neural neural circuit neurodevelopment neuronal circuitry optogenetics phenomenological models predicting response response serial imaging vestibulo-ocular reflex

项目摘要

PROJECT SUMMARY During development, animal behaviors improve as neural circuits refine. Prior work suggests that early developmental events, such as birth timing, define the role a neuron will play in a circuit. However, the complexity of most developing circuits and the behaviors they subserve limit our understanding of the role of early events in circuit maturation. My proposed experiments address this gap by asking if early development shapes circuit maturation. Defining the relationship between development and function is key to understand the how the brain and behavior mature in healthy and diseased states. The larval zebrafish is a particularly tractable model for circuit development due to its genetic accessibility, transparency, and rapid external development. Specifically, the neuronal populations driving gaze stabilization following body tilts in the larval zebrafish are well-conserved and orders of magnitude smaller. Our lab leverages these advantages to link developmental phenomenology with circuit maturation and behavior. We have established genetic and optical means to longitudinally measure and manipulate neural activity across development. Importantly, prior work from our lab has revealed that the birthdate of vestibular neurons influences anatomical location within the brainstem and preferred direction of body tilt. The goal of this proposal is to determine if birthdate similarly predicts how sensory responses mature, and if birthdate predicts a neuron’s contribution to behavior. In Aim 1, I will determine if a central vestibular neuron’s birthdate predicts its sensitivity to body tilts of different magnitudes, and/or how this encoding matures. In Aim 2, I will examine how developmentally and functionally diverse populations of vestibular neurons contribute to behavior using loss- and gain-of-function approaches. My data will define the role of early development in circuit function. Completion of these experiments will speak to the general mechanisms by which circuit function is influenced by – or indifferent to – early development.

项目总结