Cellular Mechanisms of Behavioral Development in the Vestibulospinal Circuit

前庭脊髓回路行为发展的细胞机制

• 批准号: 10331006
• 负责人: Kyla Hamling
• 金额: $ 3.85万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10331006
• 关键词: Address; Adopted; Afferent Neurons; Age; Anatomy; Animal Behavior; Animals; Axon; Bayesian Method; Behavior; Behavioral; Behavioral Mechanisms; Biological Assay; Biomechanics; Birth; Brain; Brain Stem; Calcium; Childhood; Computer Models; Data Set; Development; Disease; Equilibrium; Failure; Fishes; Functional disorder; Genetic; Goals; Health; Human; Image; Impaired health; Impairment; Individual; Knowledge; Larva; Life; Link; Mammals; Measures; Mission; Modeling; Monitor; Morphology; Movement; Musculoskeletal Equilibrium; Nervous system structure; Neurodevelopmental Disorder; Neurons; Optics; Output; Pathology; Play; Population; Postural adjustments; Posture; Property; Public Health; Reflex action; Research; Research Proposals; Resolution; Role; Rotation; Sensory; Spinal Cord; Swimming; Synapses; Testing; Time; Transgenic Organisms; Translating; United States National Institutes of Health; Vertebrates; Work; Zebrafish; associated symptom; course development; developmental disease; disabling symptom; experience; experimental study; improved; in vivo; insight; loss of function; mature animal; neural circuit; neurodevelopment; neuromechanism; optogenetics; postnatal; posture instability; relating to nervous system; response; sensorimotor system; serial imaging; symptom treatment; theories; two-photon; vestibular reflex

PROJECT SUMMARY After birth, animal behaviors mature as neural circuits refine. While the complexity of most neural circuits and their associated behaviors has meant the two are often considered separately, these phenomena are inextricably linked. Revealing how mechanisms of circuit refinement constrain behavioral improvement is critical to understanding brain development in both healthy and diseased states. Balance control is a vital sensorimotor behavior that develops postnatally according to evolutionarily conserved principles across vertebrates. The vestibulospinal circuits that maintain and correct posture also experience developmental refinement, but it is unclear how observed functional and morphological changes translate into improved posture control. The postural reflex circuit in larval zebrafish is an ideal model in which to study how cellular mechanisms of development may instantiate behavioral improvement. As simple vertebrates, zebrafish have a vestibulospinal reflex circuit that functions similarly to mammals. However, the zebrafish circuit consists of orders of magnitude fewer neurons. Our lab's efforts have established genetic and optical means to measure and manipulate neural activity non-invasively with cellular resolution across development. Furthermore, our lab has defined how postural behaviors improve with age in larval zebrafish. We have developed a control theoretic framework to understand the biomechanical underpinnings of this behavioral improvement, and to constrain the neural computations responsible for behavior. In my preliminary work, I have identified a small set of vestibulospinal neurons as a nexus of postural development in the larval fish. The goal of this research proposal is twofold: (1) to leverage the zebrafish vestibulospinal circuit to elucidate cellular mechanisms of circuit development using in vivo longitudinal imaging, and (2) to model how developing neural circuits permit concurrent behavioral improvement. In Aim 1, I will determine how sensory responses in individual vestibulospinal neurons change longitudinally across development. In Aim 2, I will identify how downstream connectivity of vestibulospinal neurons changes both anatomically and functionally during development. In Aim 3, I will adopt a computational approach to relate the encoding and decoding capacity of vestibulospinal activity across development to improvement in postural behaviors. Through the proposed work, I will define hallmarks of sensorimotor circuit development at a cellular level and relate them to their behavioral consequences. When complete, this work will define how neural circuit development gives rise to behavioral improvement.

项目概要 出生后，动物的行为随着神经回路的完善而成熟。虽然大多数神经网络的复杂性 电路及其相关行为意味着两者通常被分开考虑，这些现象 有着千丝万缕的联系。揭示电路细化机制如何限制行为改善 对于了解健康和疾病状态下的大脑发育至关重要。 平衡控制是一种重要的感觉运动行为，根据进化规律在出生后发展 脊椎动物中的保守原则。维持和纠正姿势的前庭脊髓回路也 经历发育细化，但尚不清楚如何观察到功能和形态变化 转化为改进的姿势控制。斑马鱼幼虫的姿势反射回路是一个理想的模型，其中 研究发育的细胞机制如何体现行为改善。就这么简单 与脊椎动物一样，斑马鱼也有前庭脊髓反射回路，其功能与哺乳动物相似。然而， 斑马鱼电路由数量级少的神经元组成。我们实验室的努力已经建立了遗传和 光学手段以细胞分辨率非侵入性地测量和操纵神经活动 发展。此外，我们的实验室还定义了斑马鱼幼虫的姿势行为如何随着年龄的增长而改善。 我们开发了一个控制理论框架来理解这一点的生物力学基础 行为改善，并限制负责行为的神经计算。 在我的初步工作中，我已经确定了一小部分前庭脊髓神经元作为姿势的联系 幼鱼的发育。本研究提案的目标有两个：（1）利用斑马鱼 前庭脊髓回路利用体内纵向阐明回路发育的细胞机制 成像，(2) 模拟发育中的神经回路如何同时改善行为。在目标 1 中，我 将确定单个前庭脊髓神经元的感觉反应如何纵向变化 发展。在目标 2 中，我将确定前庭脊髓神经元的下游连接如何改变两者 在发育过程中在解剖学和功能上。在目标 3 中，我将采用计算方法来关联 前庭脊髓活动的编码和解码能力，从发育到姿势改善 行为。通过拟议的工作，我将定义细胞感觉运动电路发展的标志 水平并将其与行为后果联系起来。完成后，这项工作将定义神经电路如何 发展导致行为改善。