Controlling Interareal Gamma Coherence by Optogenetics, Pharmacology and Behavior

通过光遗传学、药理学和行为控制区域间伽玛相干性

• 批准号: 8708970
• 负责人: Timothy J. Buschman
• 金额: $ 25.02万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8708970
• 关键词: Acetylcholine; Address; Affect; Animal Model; Area; Attention; Autistic Disorder; Axon; Behavior; Behavioral; Brain; Brain Diseases; Brain region; Cholinergic Agonists; Cognition; Cognitive; Communication; Complex; Computer Simulation; Coupled; Coupling; Disease; Electrophysiology (science); Equilibrium; Foundations; Frequencies; Future; Goals; Laboratories; Learning; Link; Measures; Mental disorders; Mentors; Mentorship; Methods; Modality; Monkeys; Mus; Muscarinic Agonists; Nature; Neocortex; Nicotinic Agonists; Optics; Parietal Lobe; Pharmacology; Phase; Primates; Protocols documentation; Reticular Formation; Rodent; Schizophrenia; Short-Term Memory; Somatosensory Cortex; Source; Techniques; Testing; Training; Transgenic Mice; Work; autism spectrum disorder; base; career; cholinergic; cognitive control; cognitive function; direct application; experience; flexibility; frontal lobe; human data; in vivo; insight; interest; neuromechanism; nonhuman primate; novel; optogenetics; relating to nervous system; response; skills; somatosensory

PROJECT SUMMARY/ABSTRACT Coherence between cortical regions has been implicated in cognitive functions including attention and working memory. Coherence may act to dynamically alter the routing of information through the brain, providing the flexibility that is necessary for cognition. Indeed, disruptions in coherence are linked to neural disorders such as schizophrenia and autism spectrum disorder. There has been no systematic, in vivo, study of how inter-cortical coherence arises. Here we will test the hypothesis that inter-area cortical gamma (30-80 Hz) coherence occurs when local oscillations in a source region propagate to, and synchronize with, a target region. Computational modeling predicts that the strength of pre-existing gamma in the target will affect its coherence with an incoming oscillation: 'weak' local gamma oscillations will be easily entrained, leading to coherence between the two regions, while 'strong' oscillations resist external input, making coherence difficult (unless the input matches in phase and frequency). Testing this hypothesis requires causal in vivo control of local oscillations, a technique that the Moore laboratory has recently developed utilizing optogenetics. Coupling optogenetics with multi-area recording will allow us to discover the rules of how oscillations cohere between areas. We will optogenetically induce local gamma oscillations in a source area (primary somatosensory cortex, SI) and measure their coherence with a target area (secondary somatosensory cortex, SII). We will test our hypothesis by manipulating the strength of ongoing gamma oscillations in the target in three ways. In Aim 1, we will optogenetically induce gamma oscillations in the target, parametrically varying the power and phase, in order to determine their effect on coherence. Cholinergic agonists induce gamma oscillations in the neocortex and acetylcholine may underlie the inter-areal coherence observed in attention. Therefore, in Aim 2, we will induce gamma oscillations in the target by increasing the local cholinergic tone and measuring its impact on coherence. Rodent, monkey and human data link gamma oscillations with attention. So, in Aim 3, we will test the impact of attention on the ability to optogenetically induce local gamma, and its impact on establishing coherence between areas. These aims will directly test an important hypothesis about the mechanism of inter-areal coherence. In addition, this proposal will allow me to learn optogenetic, electrophysiological, and behavioral techniques in mice, under the mentorship of Dr. Christopher Moore. My future career goals are to combine my previous primate experience with these new techniques in mice. I will use electrophysiology in primates trained to perform complex behaviors to generate hypotheses about the neural mechanisms underlying cognition. These proposed neural mechanisms can then be dissected using the powerful methods available in mice.

项目摘要/摘要 大脑皮层之间的连贯性与认知功能有关，包括注意力和 工作记忆。一致性可以起到动态改变信息通过大脑的路由的作用， 提供认知所必需的灵活性。事实上，连贯性障碍与神经有关。 精神分裂症和自闭症谱系障碍等障碍。 目前还没有关于大脑皮层间连贯性如何产生的系统的活体研究。在这里，我们将测试 假设当源中的局部振荡时发生区域间的皮质伽马(30-80赫兹)相干性 区域传播到目标区域并与目标区域同步。计算模型预测， 目标中预先存在的伽马的影响将通过进入的振荡来影响其相干性：‘弱’局部伽马 振荡很容易缠绕在一起，导致两个区域之间的一致性，而“强烈”的振荡 抵抗外部输入，使一致性变得困难(除非输入在相位和频率上匹配)。 验证这一假说需要在体内对局部振荡进行因果控制，这是摩尔 实验室最近利用光遗传学发展起来。将光遗传学与多区域记录相结合将 使我们能够发现不同区域之间的振荡是如何相互关联的。我们将通过光遗传诱导局部 震源区(初级体感皮层，SI)中的伽马振荡，并用 靶区(次级体感皮质，SII)。我们将通过操纵的强度来检验我们的假设 目标中持续的伽马振荡有三种方式。在目标1中，我们将通过光遗传诱导伽马 目标中的振荡，参数地改变功率和相位，以便确定它们对 连贯性。胆碱能激动剂诱导新皮质伽玛振荡，乙酰胆碱可能是其基础 注意中观察到的区域间的连贯性。因此，在目标2中，我们将在 通过增加局部胆碱能音调并测量其对一致性的影响来达到靶点。啮齿动物、猴子和 人类数据将伽马振荡与注意力联系在一起。因此，在目标3中，我们将测试注意力对 光遗传诱导局部伽马的能力及其对建立地区间一致性的影响。 这些目标将直接检验关于区域间一致性机制的一个重要假说。在……里面 此外，这项提议将使我能够学习光遗传学、电生理和行为技术 老鼠，在克里斯托弗·摩尔博士的指导下。我未来的职业目标是将我以前的职业生涯 灵长类动物在老鼠身上使用这些新技术的经验。我会用电生理学来训练灵长类动物 进行复杂的行为，以产生关于认知基础的神经机制的假设。这些 所提出的神经机制随后可以使用在老鼠身上可用的强大方法来剖析。