Understanding the Distributed Control of Flexible Behavior

了解灵活行为的分布式控制

• 批准号: 10640703
• 负责人: Stefan Lemke
• 金额: $ 6.95万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640703
• 关键词: Address; Angelman Syndrome; Animal Model; Animals; Area; Automobile Driving; Basal Ganglia; Behavior; Behavioral; Behavioral Model; Brain; Brain Diseases; Cerebellum; Disease; Environment; Functional disorder; Genetic Diseases; Goals; Hand; Impairment; Knockout Mice; Left; Lesion; Light; Link; Manuals; Modeling; Motor; Motor Cortex; Motor Skills; Movement; Mus; Muscle; Neural Network Simulation; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurons; Obsessive-Compulsive Disorder; Pattern; Policies; Population; Problem Solving; Production; Site; Stroke; System; Thalamic structure; Translating; UBE3A gene; Work; autism spectrum disorder; behavioral phenotyping; control theory; flexibility; imprint; insight; model design; motor control; motor deficit; mouse model; multitask; nervous system disorder; neural; neurophysiology; neuropsychiatric disorder; neuroregulation; recurrent neural network; restoration; targeted treatment; transmission process

ABSTRACT Our brains have the remarkable ability to both produce precise, consistent movements in an invariant environment and dynamically adjust behavior to a changing environment. Almost all our everyday actions, such as driving a car or riding a bike, necessitate such flexible multi-tasking. Losing the ability to flexibly adjust behavior is dramatic and debilitating, as evidenced by disorders such as obsessive-compulsive disorder (OCD) or profound forms of autism spectrum disorder (ASD). While considerable work has examined how the brain’s distributed motor network controls consistent movements in an invariant environment, the mechanisms that allow for flexibility in movement control remain unknown. In this project, I develop a behavioral model to study the flexible production of multiple distinct reaching movements in mice. The extensive previous work that has characterized the neural control of reaching movements provides a powerful framework to precisely understand the neural control of flexibility. I use this model to investigate the distributed control of flexible movements across the primary motor cortex (M1), basal ganglia (BG), and cerebellum (CB). While the M1-BG and M1-CB networks have been previously investigated in isolation, how all three regions interact is largely unexplored. I leverage (1) large-scale multi-site neurophysiology in M1, BG, and CB, (2) genetically controlled thalamic manipulations of M1-BG and M1-CB networks, (3) multi-region recurrent neural network models, and (4) mouse models of OCD and ASD that display behavioral inflexibility to uncover fundamental principles by which the brain’s distributed motor network governs flexibility in movement control and shed light on how these mechanisms dysfunction in brain disorders.

抽象的 我们的大脑具有非凡的能力，可以在不变量的情况下产生精确、一致的运动 环境并动态调整行为以适应不断变化的环境。几乎我们所有的日常行为，例如 就像开车或骑自行车一样，需要这种灵活的多任务处理。失去灵活调整的能力 强迫症 (OCD) 等疾病就证明了行为是戏剧性的、令人衰弱的 或严重形式的自闭症谱系障碍 (ASD)。虽然大量的工作已经研究了大脑如何 分布式运动网络在不变的环境中控制一致的运动，该机制允许 运动控制的灵活性仍然未知。在这个项目中，我开发了一个行为模型来研究 灵活地产生小鼠多种不同的到达动作。之前的大量工作已经 表征到达运动的神经控制提供了一个强大的框架来精确理解 灵活性的神经控制。我使用这个模型来研究跨区域灵活运动的分布式控制 初级运动皮层 (M1)、基底神经节 (BG) 和小脑 (CB)。而 M1-BG 和 M1-CB 网络 以前曾单独研究过这三个区域如何相互作用，但很大程度上尚未被探索。我杠杆（1） M1、BG 和 CB 中的大规模多部位神经生理学，(2) 基因控制的丘脑操作 M1-BG 和 M1-CB 网络，(3) 多区域循环神经网络模型，以及 (4) 强迫症小鼠模型 和自闭症谱系障碍（ASD）表现出行为僵化，以揭示大脑分布的基本原理 运动网络控制着运动控制的灵活性，并揭示了这些机制在运动过程中如何发生功能障碍。 脑部疾病。