The Role of Motor Cortex Output Circuits in Stroke Recovery

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Project Summary Stroke is one of the leading causes of adult disability. The recovery following stroke improves the patients’ long-term quality of life, but the underlying circuit mechanisms are not clear. Previous work has shown that recovery depends on undamaged brain areas, but the precise roles of the contralesional hemisphere in the recovery has been controversial: some claim that it facilitates the recovery, whereas others propose that it hampers the recovery. The lack of a consensus could be due to the lack of circuit-level analysis. The past studies treated contralesional hemisphere as a single functional unit, despite that it consists of multiple groups of neurons that project to distinct brain areas. Current proposal will test the hypothesis that cortico-spinal neurons and callosal neurons in the contralesional hemisphere have different roles in the functional recovery. In Aim 1, we will monitor longitudinally the activity of cortico- spinal neurons and callosal neurons during functional recovery. We predict that cortico-spinal neurons will show increased activity following the recovery, whereas callosal neurons do not. In Aim 2, we will examine the effect of stimulating cortico-spinal neurons and callosal neurons. We predict that activation of cortico-spinal neurons will facilitate the recovery but activation of callosal neurons will not. The current proposal will unravel the role of contralesional hemisphere at the level of neural circuits, which will advance our mechanistic understanding of recovery from stroke.