Cellular Mechanisms of Behavioral Development in the Vestibulospinal Circuit

项目摘要 出生后，动物的行为随着神经回路的完善而成熟。虽然大多数神经系统的复杂性 电路及其相关行为意味着两者通常被分开考虑，这些现象 是密不可分的揭示电路细化机制如何限制行为改善是一个重要的问题。 对理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，根据进化论， 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 转化为更好的姿态控制。斑马鱼幼鱼的姿势反射回路是一个理想的模型， 来研究细胞发育机制如何体现行为改善。那么简单 在脊椎动物中，斑马鱼具有前庭脊髓反射回路，其功能类似于哺乳动物。但 斑马鱼回路由数量级更少的神经元组成。我们实验室的努力已经建立了遗传和 光学手段来测量和操纵神经活动非侵入性与细胞分辨率跨越 发展此外，我们的实验室已经确定了姿势行为如何随着年龄的增长而改善。 我们已经开发了一个控制理论框架来理解这种生物力学基础 行为改善，并限制负责行为的神经计算。 在我的初步工作中，我已经确定了一小组前庭脊髓神经元作为姿势神经元的联系。 幼鱼的发育。这项研究提案的目标是双重的：（1）利用斑马鱼 前庭脊髓回路，以阐明电路发展的细胞机制，使用在体内纵向 成像，和（2）模型如何发展神经回路允许并发的行为改善。在目标1中， 将确定个体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 在发育过程中的解剖学和功能上。在目标3中，我将采用一种计算方法， 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，我将定义在一个细胞的感觉运动电路发展的标志， 并将其与行为后果联系起来。完成后，这项工作将定义神经回路 发展导致行为的改善。

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.