Oscillations and Resonance in Basal Ganglia Circuits

基底神经节回路中的振荡和共振

• 批准号: 9146576
• 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/9146576
• 关键词: Anatomy; Basal Ganglia; Basal Ganglia Diseases; Cell Nucleus; Characteristics; Corpus striatum structure; Discontinuous Capillary; Frequencies; Functional disorder; Knowledge; Link; Modeling; Neurodegenerative Disorders; Neurons; Output; Parkinson Disease; Periodicity; Predictive Value; Property; Signal Transduction; Substantia nigra structure; Synapses; Therapeutic; Treatment Effectiveness; base; 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一直基于电路图，该电路图勾勒出通过细胞核的电活动的流程。这些模型指导了基底神经节神经退行性疾病的治疗方法的发展，并继续对新疗法的设计和细化有用。功能模型的有效性及其在设计新处理的设计方面的预测价值与每个核中电路的准确信息紧密相关。我们对基底神经节神经元之间神经元之间的解剖连通性的了解是良好的，并且迅速改善，但是我们对电路对电活动流动的影响的理解仍处于起步阶段。在此提案中，分析了基底神经节（纹状体）主要输入核中电路的功能特征，并分析了主要输出核（底底）中的电路。这些实验使用正弦输入和正弦曲线的组合，以表征局部电路对神经元反应的影响。这些输入吸引了神经元和突触的已知共振特性，它们将揭示电路相互作用引起的其他共振。在某些实验中，输入是在电路中的细胞内或光遗传学输送到电路中的某些或所有细胞类型的，而在其他情况下，对电路的周期性输入信号是通过连续控制上游神经元的触发来传递的。这些实验将揭示在基底神经节中放大或抑制节奏活性的电路机制，包括β振荡，包括帕金森氏病的主要病理生理成分，以及在DBS期间产生的治疗性周期性信号。