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: 8027978
• 负责人: Timothy J. Buschman
• 金额: $ 8.35万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8027978
• 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; relating to nervous system; response; skills; somatosensory

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: This project will investigate how brain regions achieve coherence with one another in the gamma oscillation band. Coherence is thought to aid in the communication between brain regions, and alterations in gamma expression and in inter-areal coherence are found in several mental and brain disorders, including schizophrenia and autism. Our work may, therefore, provide insight into these maladaptive changes.

描述（申请人提供）：皮质区域之间的连贯性与包括注意力和工作记忆在内的认知功能有关。连贯性可以动态地改变通过大脑的信息路由，从而提供认知所需的灵活性。实际上，连贯性的破坏与精神分裂症和自闭症谱系障碍等神经疾病有关。 没有系统地研究皮层间相干性。在这里，我们将测试以下假设：当源区域中的局部振荡传播到目标区域并同步时，就会发生区域间皮质伽马（30-80 Hz）的连贯性。 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). 测试该假设需要因果控制局部振荡的因果，这是摩尔实验室最近利用光遗传学开发的技术。将光遗传学与多区域记录的耦合将使我们能够发现振荡如何在区域之间相处的规则。我们将在源区域（原发性体感皮层，SI）中诱导局部伽马振荡，并测量其与目标区域（二级体体皮质，SII）的相干性。我们将通过三种方式操纵目标中持续伽马振荡的强度来检验我们的假设。在AIM 1中，我们将在目标上诱导伽马振荡，参数范围改变功率和相，以确定它们对相干性的影响。胆碱能激动剂在新皮层和乙酰胆碱中诱导γ振荡可能是注意力中观察到的美术间相干性的基础。因此，在AIM 2中，我们将通过增加局部胆碱能音调并衡量其对相干性的影响来诱导靶标的γ振荡。啮齿动物，猴子和人类数据链接γ振荡引起了人们的注意。因此，在AIM 3中，我们将测试注意力对光遗传学诱导局部伽玛的能力的影响，以及其对在区域之间建立一致性的影响。 这些目的将直接检验关于美术间相干机理的重要假设。此外，该建议将使我能够在克里斯托弗·摩尔（Christopher Moore）的指导下学习小鼠的光遗传学，电生理和行为技术。我未来的职业目标是将我以前的灵长类动物体验与这些新技术相结合。我将在受过训练的灵长类动物中使用电生理学，以执行复杂的行为，以产生有关认知基础的神经机制的假设。然后可以使用小鼠可用的强大方法解剖这些提出的神经机制。 公共卫生相关性：该项目将调查大脑区域如何在伽马振荡频段中相互连贯。人们认为，连贯性有助于大脑区域之间的交流，以及在包括精神分裂症和自闭症在内的几种精神和脑部疾病中发现了伽马表达和智力间相干性的改变。因此，我们的工作可能会洞悉这些适应不良的变化。