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Voltage Imaging Analysis of Striatal Network Dynamics Related to Movement, Parkinson's Disease and Deep Brain Stimulation

与运动、帕金森病和深部脑刺激相关的纹状体网络动态的电压成像分析

基本信息

批准号：
10597209
负责人：
Xue Han
金额：
$ 39.6万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10597209
关键词：
Address Affect Anatomy Basal Ganglia Biological Markers Biophysics Brain Brain Diseases Cells Chronic Clinical Research Corpus striatum structure Deep Brain Stimulation Disease model Dopamine Dopamine Receptor Electric Stimulation Electrophysiology (science)Epilepsy Essential Tremor Event FDA approved Frequencies Functional disorder Future Goals Image Imaging Techniques Implanted Electrodes Individual Link Measures Membrane Mental disorders Modeling Motor Movement Mus Neurons Obsessive-Compulsive Disorder Optics Output Oxidopamine Parkinson Disease Pathologic Pathology Pathway interactions Patients Pattern Primates Resolution Structure Structure of subthalamic nucleus Synapses Therapeutic Therapeutic Effect Time Transgenic Mice alpha synuclein behavioral study design dopaminergic neuron imaging study insight millisecond motor disorder mouse model nervous system disorder neural circuit novel pre-formed fibril segregation voltage

项目摘要

Title: Voltage imaging analysis of striatal network dynamics related to movement, Parkinson’s disease and deep brain stimulation Summary Deep brain stimulation (DBS) delivers high frequency electrical current stimulation through chronically implanted electrodes. DBS has been FDA approved for managing several brain disorders, including Parkinson’s disease (PD), epilepsy, essential tremor, and obsessive compulsive disorders. However, the therapeutic mechanisms of DBS remain largely unknown. There are many intriguing hypothesis, but experimental evidence has been limited. The increasing use of DBS for PD over the past 20 years has offered a unique opportunity to record from various basal ganglia brain structures in patients, and accumulating evidence suggests that exaggerated pathological local field potential (LFP) beta oscillations (~10-30Hz) in the cortical-basal ganglia circuit are a signature of PD. Using exaggerated LFP beta oscillations recorded in STN as a target feature, a recent study showed that closed-loop DBS could be more effective in alleviating akinesia in primate PD models, highlighting the potential of using pathological beta oscillations as a biomarker for PD. PD is characterized by degeneration of SNpc dopamine neurons that project to the striatum. The fact that DBS is effective at managing motor pathologies highlights that PD involves neural circuit deficits that can be altered by electrical stimulation to achieve therapeutic effects. The central goal of this proposal is to study the neural circuit dynamics related to PD, and the therapeutic mechanisms of DBS, using a novel single cell voltage imaging technique that was recently developed in Dr. Han’s lab. Specifically, we will examine how individual striatal neurons’ subthreshold membrane voltage and spiking patterns relate to bulk striatal LFP oscillations during voluntary movement in healthy and dopamine-depleted PD conditions, and how DBS alters these interactions. Such understanding will provide important insights into the relationship between individual neurons subthreshold membrane voltage dynamics (a measure of synaptic inputs) and spiking outputs, and provide direct experimental evidence linking pathological LFP oscillations with single neuron biophysics, and how DBS affects these relationships. We believe that such insights will help establish oscillation based biomarkers for brain disorders, and facilitate future DBS designs.

标题：与帕金森病运动相关的纹状体网络动力学的电压成像分析