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

迷走神经刺激 (VNS) 通过时间精确的胆碱能神经调节增强运动学习

基本信息

批准号：
10454813
负责人：
Spencer Bowles
金额：
$ 2.18万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10454813
关键词：
3-Dimensional Acetylcholine Address Annual Reports Behavioral Calcium Case Study Cell Nucleus Chronic Data Devices Dissection Economic Burden Electric Stimulation Foundations Goals Human Image Implant Implanted Electrodes Interneurons Investigation Knowledge Learning Lesion Long-Term Effects Maps Mediating Motor Motor Cortex Mus Nervous System Trauma Neurons Patients Phase Phase III Clinical Trials Physical Rehabilitation Play Protocols documentation Quality of life Rehabilitation therapy Reporting Role Sensory Signal Transduction Stroke System Techniques Testing Therapeutic Therapeutic Uses Work basal forebrain cell type cholinergic cholinergic neuron clinically relevant cortex mapping deep learning algorithm effective therapy extracellular improved in vivo in vivo imaging insight kinematics motor learning motor recovery motor rehabilitation neurological rehabilitation neuromechanism neurophysiology neuroregulation novel strategies optogenetics prevent relating to nervous system stroke patient stroke rehabilitation stroke therapy therapeutically effective tool vagus nerve stimulation

项目摘要

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.

项目概要/摘要神经损伤，包括中风和创伤性脑损伤，在美国非常普遍，有数百万病例每年都有报告，并且常常导致持久的虚弱。最近的研究发现，迷走神经刺激（VNS）涉及用植入电极对迷走神经进行电刺激，可能会通过增强可塑性的机制促进神经损伤的运动康复。然而，人们对 VNS 驱动的可塑性和运动学习的机制知之甚少。之前的报道有研究表明，运动皮层神经活动在运动学习过程中发生改变，并且胆碱能系统受损可以阻止运动学习和 VNS 增强的皮质图可塑性。但是 VNS 如何调节运动电路，胆碱能信号在介导 VNS 效应中的作用仍然缺乏研究。这项工作的目的是了解 VNS 增强可塑性和运动学习的神经机制。为了解决这个问题知识差距，我建议通过 VNS 和光遗传学来操纵熟练的触及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 范围量化 VNS 和胆碱能操作对熟练达到的行为影响的轨迹。我也建议长期植入体内光极阵列来记录从 BF 到确定 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质，以确定 VNS 是否激活皮质抑制微电路。