Oscillations and Resonance in Basal Ganglia Circuits

基底神经节回路中的振荡和共振

• 批准号: 10530701
• 负责人: Charles J Wilson
• 金额: $ 66.15万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10530701
• 关键词: Anatomy; Basal Ganglia; Basal Ganglia Diseases; Cell Nucleus; Characteristics; Corpus striatum structure; Discontinuous Capillary; Frequencies; Functional disorder; Ganglia; Knowledge; Link; Modeling; Neurodegenerative Disorders; Neurons; Output; Parkinson Disease; Periodicals; Periodicity; Prediction of Response to Therapy; Predictive Value; Property; Signal Transduction; Substantia nigra structure; Synapses; Therapeutic; Treatment Effectiveness; cell type; design; experimental study; improved; infancy; next generation; optogenetics; response; signal processing; therapy development

Models of basal ganglia function and dysfunction have long been based on a circuit diagram sketching the flow of electrical activity through the nuclei. These models have guided the development of treatments for neurodegenerative diseases of the basal ganglia, and continue to be useful for design and refinement of new treatments. The validity of the functional models and their predictive value for design of new treatments is tightly linked to accurate information on the circuitry in each of the nuclei. Our knowledge of the anatomical connectivity among neurons in basal ganglia nuclei is good and improving rapidly, but our understanding of circuit effect on the flow of electrical activity is in its infancy. In this proposal, the functional characteristics of circuits in the main input nucleus of the basal ganglia (the striatum) and that in the main output nucleus (the substantia nigra) are analyzed. The experiments use sinusoidal inputs and combinations of sinusoids over a range of frequencies to characterize the effects of local circuits on neuronal responses. These inputs engage the known resonance properties of the neurons and synapses, and they will reveal other resonances that arise from circuit interactions. In some experiments, the input is intracellularly or optogenetically delivered to some or all cell-types in the circuit, whereas in others the periodic input signal to the circuit is delivered synaptically by continuously controlling firing of upstream neurons. These experiments will reveal the circuit mechanisms that amplify or suppress rhythmic activity in the basal ganglia, including both the beta oscillations that are a principal pathophysiological component of Parkinson's disease, and the therapeutic periodic signal generated during DBS.

基底神经节功能和功能障碍的模型长期以来都是基于描绘穿过细胞核的电活动流动的电路图。这些模型指导了基底神经节神经退行性疾病治疗方法的开发，并将继续有助于新治疗方法的设计和完善。功能模型的有效性及其对新疗法设计的预测价值与每个细胞核中电路的准确信息紧密相关。我们对基底神经节核中神经元之间的解剖连接的了解很好，并且正在迅速提高，但我们对电路对电活动流动的影响的理解还处于起步阶段。在该提议中，分析了基底神经节（纹状体）的主输入核和主输出核（黑质）中的电路的功能特征。实验使用一定频率范围内的正弦输入和正弦曲线组合来表征局部电路对神经元反应的影响。这些输入涉及神经元和突触的已知共振特性，并且它们将揭示电路相互作用产生的其他共振。在一些实验中，输入通过细胞内或光遗传学传递到电路中的一些或所有细胞类型，而在其他实验中，通过连续控制上游神经元的放电，将周期性输入信号传递到突触。这些实验将揭示放大或抑制基底神经节节律活动的电路机制，包括作为帕金森病主要病理生理学组成部分的β振荡，以及 DBS 期间产生的治疗周期信号。