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

前庭眼反射功能成熟的发育贡献

• 批准号: 10679875
• 负责人: Paige Leary
• 金额: $ 4.44万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679875
• 关键词: Ablation; Address; Anatomy; Animal Behavior; Animals; Automobile Driving; Behavior; Biological Assay; Birth; Birth Order; Brain; Brain Stem; Childhood; Data; Date of birth; Development; Developmental Process; Disease; Ear; Event; Eye Movements; Functional disorder; Genetic; Goals; Head; Health; Human; Image; Impaired health; Knowledge; Lesion; Link; Location; Measures; Mission; Modeling; Motor Neurons; Movement; Neurodevelopmental Disorder; Neurons; Neurosciences; Nose; Optics; Play; Population; Population Heterogeneity; Property; Protocols documentation; Public Health; Research; Role; Sensory; Shapes; System; Technology; Testing; Time; United States National Institutes of Health; Work; Zebrafish; assay development; associated symptom; developmental disease; disabling symptom; experimental study; gain of function; gaze; improved; loss of function; neural; neural circuit; neurodevelopment; neuronal circuitry; optogenetics; phenomenological models; predicting response; response; serial imaging; vestibulo-ocular reflex

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.

项目摘要 在发育过程中，动物的行为随着神经回路的完善而改善。先前的研究表明， 发育事件，如出生时间，决定了神经元在回路中的作用。但 大多数发育中的电路的复杂性和它们所支持的行为限制了我们对 电路成熟的早期事件。我提出的实验通过询问早期发育是否 形成电路成熟。定义开发和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。 由于其遗传可及性，斑马鱼幼体是电路发育的特别易处理的模型， 透明度和快速的外部发展。具体来说，驱动凝视稳定的神经元群体 随后的身体倾斜在斑马鱼幼虫中是很好的保守和数量级较小。我们实验室 利用这些优势将发育现象学与回路成熟和行为联系起来。我们 已经建立了遗传和光学手段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已经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。 这项提议的目的是确定出生日期是否同样预测了感官反应 成熟，如果出生日期预测神经元对行为的贡献。在目标1中，我将确定 前庭神经元的出生日期预测了它对不同幅度的身体倾斜的敏感性，和/或这是如何发生的。 编码成熟。在目标2中，我将研究发育和功能多样性的人群是如何发展的。 前庭神经元使用功能丧失和获得方法对行为作出贡献。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 回路功能受早期发育影响或不受影响的机制。