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

• 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
• 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

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.

项目总结/文摘