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，研究人员观察到在新皮层的节奏电活动，即覆盖哺乳动物大脑的神经元的外壳。尽管这些振荡的普遍性，但它们的计算含义（如果以及它们如何帮助我们移动，感知和/或思考）是激烈辩论的话题。 β振荡，15＆＃8208; 29 Hz的节奏活动在新皮层中很突出。 β的过表达是帕金森氏病的标志，缓解运动症状的治疗方法也减少了β。同样，β振荡预测了人类受试者感知感觉刺激的失败。这些发现直接暗示Beta对于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疗法至关重要。本研究将检验一个最近开发的假设，该假设解释了人脑中β的自然表达模式。该假设来自详细的生物物理准确和多＆多＆＃8208;区域计算神经模型。为了检验这一假设，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。这些数据依次将用于推进和约束模型。作为这项研究的一部分，该模型将被详细说明，包括基底神经节，丘脑和新皮层的互连元素。这些区域将是神经记录的目标，以了解其活性与麻醉和表现准备的处理感觉信息的新皮层β的相关性。通过利用光遗传学的最新创新，光脉冲以毫秒的精度和细胞型特异性打开神经元的应用来实现模型预测的因果测试。光遗传学将在真实的大脑中测试该模型预测的活性模式的充分性和必要性，以导致这种大脑节奏的表达。