CRCNS Research Proposal: Contributions of the Thalamus and Basal Ganglia to Neocortical Beta Oscillation: A Novel Computational Hypothesis

CRCNS 研究提案：丘脑和基底神经节对新皮质 Beta 振荡的贡献：一种新颖的计算假设

• 批准号: 1131850
• 负责人: Christopher Moore
• 金额: $ 83万
• 依托单位: Brown University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-11-01 至 2014-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1131850&HistoricalAwards=false
• 关键词: CRCNS; Research; Proposal; Contributions; Thalamus

For over 80 years, researchers have observed rhythmic electrical activity in the neocortex, the outer shell of neurons covering the mammalian brain. Despite the prevalence of these oscillations, their meaning for computation--if and how they help us move, perceive and/or think--is a topic of intense debate. Beta oscillations, rhythmic activity at 15‐29 Hz, are prominent in neocortex. Overexpression of beta is a hallmark of Parkinson's disease, and treatments that relieve its motor symptoms also diminish beta. Similarly, beta oscillations predict failure by human subjects to perceive sensory stimuli. These findings directly implicate beta as important for information processing and healthy brain function. Understanding the detailed origins of beta is crucial to knowing its role and to potentially guiding targeted therapies.The present study will test a recently developed hypothesis that explains the natural expression patterns of beta in the human brain. This hypothesis emerged from a detailed biophysically accurate and multi‐area computational neural model. To test this hypothesis, the proposed research will use detailed simulations of multiple brain areas to guide experimental recordings and brain stimulation. These data will in turn be used to advance and constrain the model. As part of this research, the model will be elaborated to include interconnected elements from the basal ganglia, thalamus and neocortex.These same areas will be targets for neural recording, to understand how their activity correlates with neocortical beta in anesthetized and behaving preparations processing sensory information. Causal testing of model predictions will be achieved by leveraging recent innovations in optogenetics, the application of light pulses to turn neurons on and off with millisecond precision and cell-type specificity. Optogenetics will test in a real brain the sufficiency and necessity of the activity patterns that are predicted by the model to lead to expression of this brain rhythm.

80多年来，研究人员一直在观察新皮层（覆盖哺乳动物大脑的神经元外壳）中有节奏的电活动。尽管这些振荡很普遍，但它们对计算的意义--它们是否以及如何帮助我们移动、感知和/或思考--是一个激烈争论的话题。β振荡，在15 #8208;29赫兹的节奏活动，是突出的新皮层。β过度表达是帕金森病的一个标志，缓解其运动症状的治疗也会减少β。类似地，β振荡预测人类受试者感知感官刺激的失败。这些发现直接暗示β对信息处理和健康的大脑功能很重要。了解β的详细起源对于了解其作用和潜在的指导靶向治疗至关重要。本研究将测试最近开发的一种假说，该假说解释了β在人脑中的自然表达模式。这一假设出现了一个详细的生物病理学准确和多#8208;区域计算神经模型。为了验证这一假设，拟议的研究将使用多个大脑区域的详细模拟来指导实验记录和大脑刺激。这些数据将反过来用于推进和约束模型。作为这项研究的一部分，该模型将包括来自基底神经节、丘脑和新皮层的相互关联的元素，这些相同的区域将成为神经记录的目标，以了解它们的活动如何与处理感觉信息的麻醉和行为准备中的新皮层β相关。模型预测的因果测试将通过利用光遗传学的最新创新来实现，光脉冲的应用以毫秒级的精度和细胞类型特异性打开和关闭神经元。光遗传学将在真实的大脑中测试模型预测的导致这种大脑节律表达的活动模式的充分性和必要性。