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.

项目总结/摘要 皮质区域之间的一致性已经涉及认知功能，包括注意力和 工作记忆连贯性可以动态地改变信息通过大脑的路径， 提供认知所需的灵活性。事实上，连贯性的中断与神经系统的 精神分裂症和自闭症谱系障碍。 目前还没有系统的，在体内，皮层间的连贯性如何产生的研究。在这里我们将测试 假设区域间皮层伽马（30-80 Hz）相干性发生时，在一个源的本地振荡 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将影响其与传入振荡的相干性：“弱”局部伽马 振荡将很容易夹带，导致两个区域之间的相干性，而“强”振荡 抵抗外部输入，使得相干性困难（除非输入在相位和频率上匹配）。 检验这一假设需要在体内控制局部振荡的因果关系，这是摩尔 实验室最近开发了利用光遗传学。将光遗传学与多区域记录相结合， 让我们能够发现区域间振荡的规律。我们将光遗传学诱导局部 在源区域（初级躯体感觉皮层，SI）中的伽马振荡，并测量它们与 次级躯体感觉皮层（secondary somatosensory cortex，SII）我们将通过操纵 目标中持续的伽马振荡有三种方式在目标1中，我们将通过光遗传学诱导γ 目标中的振荡，参数地改变功率和相位，以确定它们对 连贯性胆碱能激动剂诱导新皮层γ振荡，乙酰胆碱可能是其基础。 注意力的区域间一致性。因此，在目标2中，我们将在 通过增加局部胆碱能张力并测量其对连贯性的影响来实现目标。啮齿动物、猴子和 人类数据将伽马振荡与注意力联系起来。因此，在目标3中，我们将测试注意力对 光遗传学诱导局部γ的能力，以及其对建立区域之间的相干性的影响。 这些目标将直接检验关于地区间协调机制的一个重要假设。在 此外，这个建议将使我能够学习光遗传学，电生理学和行为技术， 在克里斯托弗摩尔博士的指导下，我未来的职业目标是把我以前的联合收割机 灵长类动物在老鼠身上的实验。我将在灵长类动物身上使用电生理学， 执行复杂的行为，以产生关于认知的神经机制的假设。这些 提出的神经机制，然后可以解剖使用强大的方法在小鼠。