Cellular and Neural Network Mechanism of Transcranial Electric Stimulation

经颅电刺激的细胞和神经网络机制

基本信息

批准号：
10338804
负责人：
DOMINIQUE M DURAND
金额：
$ 116.25万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
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：
2021-09-22 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10338804
关键词：
Affect Animals BRAIN initiative Behavior Biology Biophysics Brain Brain region Clinical Trials Cognition Coupling Development Disease Electric Stimulation Electrodes Electrophysiology (science)Epilepsy Extracellular Space Goals Hippocampus (Brain)Image Imaging Techniques In Vitro Laboratories Link Measures Mediating Methods Microdialysis Modality Neurons Osmolar Concentration Play Protocols documentation Reporting Research Role Seizures Sleep Slice Speed Synaptic Transmission Techniques Technology Testing Therapeutic Transgenic Mice base behavioral study clinical application cognitive performance electric field experimental study extracellular improved in vivo insight motor disorder neural network neural recruitment neural stimulation neuromechanism neuroregulation novel optogenetics recruit relating to nervous system response success voltage

项目摘要

Unveiling mechanisms of neural stimulation technologies is an important goal of the Brain Initiative (RFA-NS-20-006). Transcranial electric stimulation (TES) is a non-invasive neuromodulation technique to provide wide-range effects on seizure control, behaviors, and cognition by generating weak electric fields in the brain. It is still an open question of how these weak electric fields can interact effectively with neural activity, and the mechanism of action of TES is still unknown. Our laboratory has recently found that ephaptic coupling (non-synaptic neural coupling by electric fields) plays a significant role in neural recruitment and could possibly explain the TES-induced effects. We propose to test the hypothesis that ephaptic coupling is the mechanism of action of TES. With the combination of in-vitro novel voltage imaging techniques and optogenetic stimulation in the transgenic mice and in-vivo electrophysiological experiments, we will study the links between the ephaptic coupling and three known TES-induced effects in the following independent specific aims: 1) Investigate the role of ephaptic coupling in TES-induced propagation speed modulation of interictal spikes. 2) Determine the role of ephaptic coupling in TES-induced seizure suppression. 3) Study the role of ephaptic coupling in TES-induced effects on neural oscillations. This proposal, if successful, will provide a novel insight into TES-induced effects, reveal the mechanism of action of TES, and open the door to the development of improved TES protocols with improved efficiency for this non-synaptic therapeutic modality.

揭示神经刺激技术的机制是大脑计划 (RFA-NS-20-006) 的一个重要目标。经颅电刺激 (TES) 是一种非侵入性神经调节技术，通过在大脑中产生微弱电场，对癫痫控制、行为和认知产生广泛的影响。这些弱电场如何与神经活动有效相互作用仍然是一个悬而未决的问题，TES 的作用机制仍然未知。我们的实验室最近发现突触耦合（电场的非突触神经耦合）在神经募集中发挥着重要作用，并且可能解释 TES 引起的效应。我们建议检验触觉耦合是 TES 作用机制的假设。通过结合体外新型电压成像技术和转基因小鼠的光遗传学刺激以及体内电生理实验，我们将在以下独立的具体目标中研究触觉耦合与三种已知的 TES 诱导效应之间的联系：1）研究触觉耦合在 TES 诱导的发作间期尖峰传播速度调节中的作用。 2) 确定触觉耦合在 TES 诱导的癫痫发作抑制中的作用。 3) 研究触觉耦合在 TES 诱导的神经振荡效应中的作用。该提案如果成功，将为 TES 诱导的效应提供新的见解，揭示 TES 的作用机制，并为开发改进的 TES 方案打开大门，提高这种非突触治疗方式的效率。