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

项目概要/摘要 神经损伤，包括中风和TBI，在美国非常普遍，有数百万例 每年报告一次，经常导致持久的衰弱。最近的研究发现迷走神经 涉及用植入电极电刺激迷走神经的迷走神经刺激（VNS）可以 通过增强可塑性的机制促进神经损伤的运动康复。然而，在这方面， 对VNS驱动的可塑性和运动学习的机制知之甚少。以前的报告 表明在运动学习和胆碱能系统损伤过程中运动皮层神经活动改变 可以阻止运动学习和VNS增强的皮层地图可塑性。但迷走神经刺激系统是如何调节运动回路的， 并且胆碱能信号在介导VNS效应中所起的作用仍缺乏研究。这项工作旨在 了解VNS增强可塑性和运动学习的神经机制。为了解决这个 知识的差距，我建议用VNS和光遗传学来操纵熟练到达任务的学习 胆碱能操纵使用深度学习算法的最新进展，我将记录3D范围 轨迹来量化VNS和胆碱能操纵对熟练伸手的行为影响。我也 建议长期植入体内光电极阵列，以记录BF的单单位神经活动， 确定VNS是否直接改变BF活性。最后，我建议在运动中使用细胞类型特异性钙成像， 皮层，以确定VNS是否激活皮层抑制性微电路。

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.