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

项目总结 在发育过程中，随着神经回路的完善，动物的行为会得到改善。先前的研究表明，早期 发育事件，如出生时间，决定了神经元在回路中扮演的角色。然而， 大多数正在开发的电路及其所伴随的行为的复杂性限制了我们对 电路成熟的早期事件。我提出的实验解决了这一差距，通过询问早期开发 塑造电路的成熟度。界定发展与功能之间的关系是理解 大脑和行为在健康和疾病状态下是如何成熟的。 斑马鱼幼体由于其遗传可及性，是回路发育的一个特别容易驯化的模型， 透明度，以及快速的外部发展。具体地说，驱动凝视稳定的神经元群体 在幼体倾斜之后，斑马鱼保存良好，数量级较小。我们的实验室 利用这些优势将发展现象学与电路成熟和行为联系起来。我们 已经建立了基因和光学方法来纵向测量和操纵神经活动 发展。重要的是，我们实验室之前的工作揭示了前庭神经元的出生日期 影响脑干内的解剖位置和身体倾斜的首选方向。 这项提议的目标是确定生日是否同样能预测感官反应 成熟，如果出生日期预测了神经元对行为的贡献。在目标1中，我将确定一个中央 前庭神经元的出生日期预测它对不同程度的身体倾斜的敏感性，和/或如何 编码技术成熟了。在目标2中，我将研究发育和功能多样化的人口是如何 前庭神经元使用功能丧失和功能获得的方法来促进行为。我的数据将定义 早期发育在电路功能中的作用。这些实验的完成将对将军说 电路功能受早期发育影响或不受其影响的机制。

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.