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：
10313783
负责人：
Spencer Bowles
金额：
$ 3.43万
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 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10313783
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.

项目摘要/摘要神经损伤，包括中风和TBI的神经伤害，在美国高度普遍存在，数百万个病例每年报告，并且通常会导致持久的衰弱。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的电刺激，可能通过增强的可塑性机制从神经损伤中促进运动康复。然而，关于基础VNS驱动的可塑性和运动学习的机制知之甚少。以前的报告有表明运动皮层神经活动在运动学习过程中发生了变化和胆碱能系统的病变可以防止运动学习和VNS增强的皮质图可塑性。但是VNS如何调节电路，胆碱能信号在介导VNS效应中的作用仍然很糟糕。这项工作旨在了解潜在的VNS增强可塑性和运动学习的神经机制。解决这个问题知识差距，我建议用VN和光学遗传来操纵学习熟练的触手可及任务胆碱能的操纵。使用深度学习算法中的最新进步，我将记录3D覆盖范围量化行为影响VN和胆碱能的操纵的轨迹对熟练的到达。我也是提议长期植入体内选项阵列，以记录从BF到的单单元神经活动确定VNS是否直接改变BF活动。最后，我建议在电动机中使用细胞类型特异性钙成像皮层，确定VNS是否激活皮质抑制微电路。