Neural basis of movement in health and disease

健康和疾病运动的神经基础

• 批准号: 10828542
• 负责人: Cera Hassinan
• 金额: $ 4.39万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-09-14
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10828542
• 关键词: Adolescence; Adult; Animal Model; Animals; Behavior; Behavioral; Biological Models; Caenorhabditis elegans; Collection; Development; Disease; Foundations; Functional disorder; Gait; Genetic; Health; Human; Image; Individual; Investigation; Knowledge; Locomotion; Locomotor adaptation; Maintenance; Molecular; Motor; Movement; Nervous System Trauma; Neurons; Pathway interactions; Periodicity; Phase; Postdoctoral Fellow; Predisposition; Process; Regulation; Research; Research Personnel; Research Training; Risk; Role; Scientist; Shapes; Solid; Techniques; Time; Work; awake; connectome; course development; effective therapy; innovation; insight; juvenile animal; mature animal; model organism; motor control; motor disorder; mouse model; nervous system disorder; neural; neural circuit; neural network; pre-doctoral; programs; skill acquisition; supportive environment; tool

PROJECT SUMMARY AND ABSTRACT Movement is a fundamental component of behavior that is established and refined throughout development into adulthood. Over the course of a lifetime, our capacity to move is susceptible to neurological disorders and injuries that can pose significant and sometimes fatal risks to human health. This proposal aims to elucidate the underlying molecular mechanisms governing the establishment, maintenance, and adaptation of locomotor behaviors and their disruptions in disease. Utilizing advanced techniques, including genetics, imaging, neuronal tracing, and circuit manipulations, I will investigate motor regulation in awake, behaving animals. My predoctoral and postdoctoral research training will provide a solid foundation for me to become an independent investigator equipped with the knowledge and expertise to uncover essential principles governing motor regulation in health and disease. My predoctoral research focuses on developmental pathways that guide the formation of neural circuits capable of producing rhythmic locomotion. I have chosen the model organism C. elegans for my predoctoral research due to its strengths, including a well-defined time course of development, a collection of powerful genetic tools, a fully resolved connectome, and an array of naturalistic behaviors available for study. Research in Aim 1 (F99 phase) will elucidate the development and regulation of rhythmic locomotion in C. elegans. I hypothesize that individual Wnt pathways have specific roles in programming neural circuits for locomotion and gait transitions in juvenile and adult animals. My predoctoral studies will introduce technical and intellectual innovations to the investigation of locomotor regulation, providing critical insights into the genetic programs necessary for the establishment and maturation of rhythmic locomotion at various developmental stages. In Aim 2 (K00 phase), I will identify a postdoctoral program focusing on mammalian neural circuits for motor control. Research training in the K00 phase will allow me to gain expertise in mouse models of motor regulation and dysfunction. I will work with my supervisory committee and sponsor to identify postdoctoral labs with a supportive environment for my progression into independent research. Upon completion of these Aims, I will have acquired the skills and knowledge to transition into an independent scientist role, where I will conduct foundational research in motor circuit development and regulation, uncovering motor disorder processes and potential therapies.

项目概要和摘要 运动是行为的基本组成部分，是在发育过程中建立和完善的 成年期。在一生中，我们的移动能力很容易受到神经系统疾病和损伤的影响 这可能对人类健康造成重大甚至有时致命的风险。该提案旨在阐明 控制运动建立、维持和适应的潜在分子机制 行为及其对疾病的干扰。利用先进技术，包括遗传学、成像、神经元 跟踪和电路操作，我将研究清醒的、有行为的动物的运动调节。我的博士前 博士后研究训练将为我成为一名独立研究者提供坚实的基础 具备揭示健康运动调节基本原则的知识和专业知识 和疾病。我的博士前研究重点是指导神经形成的发育途径 能够产生有节奏运动的电路。我选择了模式生物秀丽隐杆线虫作为我的 博士前研究因其优势，包括明确的发展时间进程、一系列 强大的遗传工具、完全解析的连接组以及一系列可供研究的自然行为。 目标 1（F99 阶段）的研究将阐明线虫节律运动的发展和调节。 线虫。我假设各个 Wnt 通路在神经回路编程中具有特定作用 幼年和成年动物的运动和步态转变。我的博士前研究将介绍技术和 运动调节研究的智力创新，为遗传提供了重要的见解 在不同发育阶段建立和成熟有节奏的运动所必需的程序 阶段。在目标 2（K00 阶段）中，我将确定一个专注于哺乳动物神经回路的博士后项目 电机控制。 K00 阶段的研究培训将使我获得小鼠运动模型方面的专业知识 调节和功能障碍。我将与我的监督委员会和赞助商合作确定博士后实验室 为我进入独立研究提供支持性环境。完成这些目标后，我 将获得转变为独立科学家角色的技能和知识，我将在其中进行 运动回路发育和调节的基础研究，揭示运动障碍过程和 潜在的疗法。