Systematic Testing of a Neocortical Gamma Gain Hypothesis

新皮质伽玛增益假说的系统测试

• 批准号: 8657000
• 负责人: Christopher Allen Deister
• 金额: $ 5.51万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8657000
• 关键词: Animals; Area; Attention; Behavioral; Brain; Cells; Code; Cognitive; Communication; Data; Detection; Disease; Electrodes; Goals; Head; Image; Link; Motor Cortex; Mus; Neocortex; Neurons; Neurosciences; Preparation; Role; Running; Schizophrenia; Sensory; Shapes; Signal Transduction; Slice; Somatosensory Cortex; Testing; Time; autism spectrum disorder; awake; barrel cortex; base; extracellular; improved; neocortical; neuronal cell body; optogenetics; public health relevance; sensory stimulus; theories; two-photon

DESCRIPTION (provided by applicant): Rhythmic brain activity has been a focus of neuroscience for more than a century. Gamma rhythms are fast rhythms (30-80 Hz) seen throughout the brain, including in the neocortex. Gamma has been implicated in a number of disorders, particularly schizophrenia, but recent links to autism spectrum disorder have been made. Gamma has been implicated in a variety of normal neocortical functions, such as allocation of attention, sensory detection and facilitating intracortical communication. Leading theoretical proposals for how gamma influences these correlated phenomena have relied on controversial timing-based arguments. Recent data supports an alternative hypothesis, that gamma facilitates cortico-cortical communication by selectively increasing the excitability of layer V neurons (a specific class of cortico-cortical neurons) locally. I will systematically test his recent hypothesis in four complementary ways. First, I will characterize the impact of endogenous and evoked gamma on layer V cell activity in primary somatosensory cortex (SI) of awake mice (gamma's impact on intra-area gain). Second, I will determine if the particular layer V cells that project to motor cortex (MI) are modulated by gamma (gamma's impact on inter-areal gain). Third, I will determine if SI gamma facilitates activity of neurons in MI that receive inputs from SI. Fourth, I will study the behavioral impact of evoked SI gamma on a sensory detection task that involves SI to MI communication, and try to mimic the effects of SI gamma by direct layer V cell depolarization (gamma's impact on behavioral gain). These results will improve our understanding of basic neocortical communication, but should also serve as an important direct test of gamma's hypothesized actions in the brain.

描述（由申请人提供）：一个多世纪以来，节律性大脑活动一直是神经科学的焦点。伽玛节律是整个大脑（包括新皮质）中可见的快节律（30-80 Hz）。伽玛与许多疾病有关，特别是精神分裂症，但最近也发现它与自闭症谱系障碍有关。伽玛与多种正常的新皮质功能有关，例如注意力分配、感觉检测和促进皮质内交流。关于伽马如何影响这些相关现象的主要理论建议依赖于有争议的基于时间的论点。最近的数据支持另一种假设，即伽马通过选择性地增加局部 V 层神经元（一类特定的皮质-皮质神经元）的兴奋性来促进皮质-皮质间的通信。我将以四种互补的方式系统地检验他最近的假设。首先，我将描述内源性和诱发性伽马对清醒小鼠初级体感皮层 (SI) V 层细胞活动的影响（伽马对区域内增益的影响）。其次，我将确定投射到运动皮层 (MI) 的特定 V 层细胞是否受到伽马调制（伽马对区域间增益的影响）。第三，我将确定 SI 伽玛是否促进 MI 中接收信号的神经元的活动 来自 SI 的输入。第四，我将研究诱发 SI 伽玛对涉及 SI 到 MI 通信的感觉检测任务的行为影响，并尝试通过直接 V 层细胞去极化（伽玛对行为增益的影响）来模拟 SI 伽玛的影响。这些结果将提高我们对基本新皮质通讯的理解，但也应该作为对大脑中伽玛假设作用的重要直接测试。