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.

摘要 我们的大脑具有非凡的能力，能够在不变量中产生精确、一致的运动 环境，并根据不断变化的环境动态调整行为。我们几乎所有的日常行为，比如 就像开车或骑自行车一样，这种灵活的多任务处理是必要的。失去了灵活调整的能力 行为是戏剧性的，令人虚弱，强迫症(OCD)等障碍就是明证。 或严重形式的自闭症谱系障碍(ASD)。虽然相当多的研究已经研究了大脑是如何 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 对于运动控制的灵活性，目前还不清楚。在这个项目中，我开发了一个行为模型来研究 在小鼠身上灵活地产生多种不同的伸展运动。之前大量的工作已经完成 描述了神经控制伸展运动的特征为准确理解 灵活性的神经控制。我使用这个模型来研究灵活移动的分布式控制 初级运动皮质(M1)、基底节(BG)和小脑(CB)。而M1-BG和M1-CB网络 以前都是单独研究的，但这三个区域如何相互作用在很大程度上还没有被探索。I杠杆(1) M1、BG和CB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)多区域递归神经网络模型；(4)强迫症小鼠模型 和自闭症，表现出行为上的僵化，以揭示大脑分布的基本原则 运动网络控制着运动控制的灵活性，并阐明了这些机制如何在 大脑紊乱。