Understanding the Distributed Control of Flexible Behavior

点击翻译按钮获取中文摘要

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.