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.

项目摘要和摘要 动作是行为的基本组成部分，它在整个发展过程中被确立和提炼成 成人期。在一生中，我们的行动能力容易受到神经紊乱和损伤的影响 这可能会对人类健康构成重大、有时甚至是致命的风险。这项建议旨在澄清 控制运动建立、维持和适应的潜在分子机制 疾病中的行为及其干扰。利用先进的技术，包括遗传学、成像、神经学 追踪和电路操作，我将研究清醒、行为正常的动物的运动调节。我的博士前 博士后研究培训将为我成为一名独立调查员提供坚实的基础 具备知识和专业知识，以揭示健康中运动调节的基本原则 和疾病。我的博士前研究重点是引导神经形成的发育途径 能够产生有节奏的运动的电路。我选择了模型生物线虫作为我的 博士前研究由于其优势，包括定义明确的开发时间进程，收集 强大的遗传工具，完全分解的连接体，以及一系列可供研究的自然行为。 目标1(F99期)的研究将阐明C。 优雅女装。我假设单独的Wnt通路在编程神经回路中具有特定的作用 幼年和成年动物的运动和步态转换。我的博士前研究将介绍技术和 对运动调节研究的智力创新，提供了对遗传学的关键见解 节奏性运动在不同发育阶段建立和成熟所必需的程序 各阶段。在目标2(K00阶段)，我将确定一个博士后项目，重点是研究哺乳动物的神经回路 马达控制。K00阶段的研究培训将使我在运动的鼠标模型方面获得专业知识 监管和功能失调。我将与我的监督委员会和赞助商合作，确定博士后实验室 有一个支持我进入独立研究的环境。在完成这些目标后，我 我将获得过渡到独立科学家角色的技能和知识，我将在那里进行 马达电路开发和调节的基础研究，揭示马达紊乱的过程和 潜在的治疗方法。