The Role of Motor Cortex Output Circuits in Stroke Recovery

项目摘要 中风是成人残疾的主要原因之一。中风后的恢复改善 患者的长期生活质量，但潜在的电路机制尚不清楚。 以前的研究表明，恢复取决于未受损的大脑区域，但精确的 对侧损伤半球在恢复中的作用一直存在争议：有人声称， 促进复苏，而另一些人则认为它阻碍了复苏。缺乏一个 共识可能是由于缺乏电路级分析。过去的研究认为， 对侧半球作为一个单一的功能单位，尽管它由多组 神经元投射到不同的大脑区域。目前的提议将检验以下假设： 皮质脊髓神经元和胼胝体神经元在对侧半球有不同的 在功能恢复中的作用。在目标1中，我们将纵向监测皮质的活动， 脊髓神经元和胼胝体神经元的功能恢复。我们预测皮质脊髓 神经元在恢复后将显示出增加的活性，而胼胝体神经元则不会。在 目的2：观察刺激皮质脊髓神经元和胼胝体神经元的效应。我们 预测皮质脊髓神经元的激活将促进恢复， 胼胝体神经元则不会。目前的建议将阐明对侧半球的作用， 在神经回路的水平上，这将促进我们对恢复的机械理解 中风

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.