Vagus nerve stimulation (VNS) enhances motor learning through temporally-precise cholinergic neuromodulation

项目摘要/摘要 神经损伤，包括中风和脑外伤，在美国非常普遍，有数百万例 每年报告一次，通常会导致持久的虚弱。最近的研究发现，迷走神经 刺激(VNS)，涉及到用植入的电极电刺激迷走神经，可能会 通过增强可塑性的机制促进神经损伤后的运动康复。然而， 对VNS驱动的可塑性和运动学习不足的机制知之甚少。此前的报道称 显示在运动学习和胆碱能系统受损的过程中，运动皮质神经活动发生改变 可以防止运动学习和VNS增强的皮层MAP可塑性。但VNS如何调制马达电路， 而胆碱能信号在介导VNS效应中所起的作用还很少被研究。这项工作旨在 了解VNS增强可塑性和运动学习的神经机制。要解决这个问题 知识上的差距，我建议用VNS和光遗传学来操纵一个熟练的REACH任务的学习 胆碱能操纵。利用深度学习算法的最新进展，我将记录3D Reach 量化VNS和胆碱能操作对熟练伸展的行为影响的轨迹。我也是 建议在体内长期植入光电极阵列以记录从BF到BF的单单位神经活动 确定VNS是否直接改变BF活动。最后，我建议在马达中使用细胞型特异性钙成像。 以确定迷走神经是否激活皮层抑制微回路。

Project Summary/Abstract Neurological injuries, including those from stroke and TBI, are highly prevalent in the US with millions of cases reported annually and often result in lasting debilitation. Recent studies have found that vagus nerve stimulation (VNS), which involves electrical stimulation of the vagus nerve with an implanted electrode, may to facilitate motor rehabilitation from neurological injury through mechanisms of enhanced plasticity. However, little is known about mechanisms that underly VNS-driven plasticity and motor learning. Previous reports have shown that motor cortex neural activity is altered during motor learning and that lesion of cholinergic systems can prevent motor learning and VNS-enhanced cortical map plasticity. But how VNS modulates motor circuits, and the role cholinergic signaling plays in mediating VNS effects remains poorly studied. This work aims to understand the neural mechanism that underly VNS-enhanced plasticity and motor learning. To address this gap in knowledge, I am proposing to manipulate learning of a skilled reach task with VNS and optogenetic cholinergic manipulation. Using recent advancements in deep learning algorithms I will record 3D reach trajectory to quantify the behavioral impact VNS and cholinergic manipulation have on skilled reaching. I also propose to chronically implanted in vivo optetrode arrays to record single-unit neural activity from the BF to determine if VNS alters BF activity directly. Lastly, I propose use cell-type specific calcium imaging in the motor cortex, to determine if VNS activates cortical inhibitory microcircuits.