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Cellular Mechanisms of Behavioral Development in the Vestibulospinal Circuit

前庭脊髓回路行为发展的细胞机制

基本信息

批准号：
10594990
负责人：
Kyla Hamling
金额：
$ 2.8万
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：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2023-10-21
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10594990
关键词：
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 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 Symptoms 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 neural circuit neurodevelopment neuromechanism neuronal circuitry optogenetics postnatal posture instability response sensorimotor system serial imaging theories two-photon vestibular reflex

项目摘要

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.

项目总结出生后，动物的行为随着神经回路的完善而成熟。而大多数神经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。揭示了电路优化机制如何限制行为改进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，它是在出生后根据进化过程发展起来的脊椎动物的守恒原则。维持和纠正姿势的前庭脊髓回路也经历发育完善，但尚不清楚观察到的功能和形态变化转化为更好的姿势控制。斑马鱼幼体的姿势反射回路是一种理想的模型研究发育的细胞机制如何实例化行为改善。一样简单脊椎动物斑马鱼的前庭脊髓反射回路的功能与哺乳动物相似。然而，斑马鱼环路由数量较少的神经元组成。我们实验室的努力已经确定了基因和光学手段，非侵入性地测量和操纵神经活动，细胞分辨率跨发展。此外，我们的实验室已经确定了斑马鱼幼体的姿势行为是如何随着年龄的增长而改善的。我们开发了一个控制理论框架来理解其生物力学基础。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是幼鱼的发育。这项研究提案的目的有两个：(1)利用斑马鱼用活体纵向研究前庭脊髓回路发育的细胞机制成像，以及(2)对发育中的神经回路如何允许同时改善行为进行建模。在目标1中，我将决定单个前庭脊髓神经元的感觉反应是如何纵向变化的发展。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在发育过程中从解剖和功能上讲。在目标3中，我将采用计算方法将从发育到姿势改善的前庭脊髓活动的编码和解码能力行为。通过这项拟议的工作，我将在细胞中定义感觉运动电路发展的特征并将其与其行为后果联系起来。完成后，这项工作将定义神经回路如何发展会带来行为的改善。