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.

项目摘要 出生后，动物行为随着神经回路的成熟而成熟。而大多数神经的复杂性 电路及其相关的行为意味着两者通常被单独考虑，这些现象 是无情的链接。揭示电路改进的机制如何限制行为改善是如何的 了解健康和患病状态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，在产后根据进化而发展 跨脊椎动物的保守原理。维护和纠正姿势的前庭脊髓脊髓电路 经验发展的精致，但尚不清楚观察到的功能和形态变化如何 转化为改进的姿势控制。幼虫斑马鱼中的姿势反射电路是理想的模型 研究细胞发育机制如何实例化行为改善。很简单 脊椎动物，斑马鱼具有与哺乳动物相似的前庭脊髓反射回路。但是， 斑马鱼电路由较少的神经元组成。我们实验室的努力已经建立了遗传和 光学手段，以跨性细胞分辨率在跨性细胞分辨率的情况下测量和操纵神经活动 发展。此外，我们的实验室定义了姿势行为如何随着幼虫斑马鱼的年龄改善。 我们已经开发了一个控制理论框架，以了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，我确定了一小部分前庭脊髓神经元是姿势的联系 幼虫鱼的发育。该研究建议的目标是双重的：（1）利用斑马鱼 前庭脊髓脊髓回路阐明了使用体内纵向的电路发育的细胞机制 成像，（2）模拟发展神经回路如何允许同时改善行为。在AIM 1中，我 将确定单个前庭脊髓神经元中的感觉反应如何在纵向上变化 发展。在AIM 2中，我将确定前庭脊髓神经元的下游连通性如何改变 在开发过程中在解剖学和功能上。在AIM 3中，我将采用一种计算方法来关联 整个开发过程中前庭脊髓活动的编码和解码能力以改善姿势 行为。通过拟议的工作，我将在细胞处定义感觉运动电路发育的标志 将它们与他们的行为后果联系起来。完成后，这项工作将定义神经电路 发展带来行为改善。