Systematic Testing of a Neocortical Gamma Gain Hypothesis

描述（由申请人提供）：节律性脑活动已经成为神经科学的焦点超过世纪。伽马节律是在整个大脑（包括新皮层）中看到的快速节律（30-80 Hz）。伽马与许多疾病有关，特别是精神分裂症，但最近与自闭症谱系障碍有关。伽马参与了各种正常的新皮质功能，如注意力分配、感觉检测和促进皮质内通信。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γ通过选择性地增加局部V层神经元（一种特定的皮质-皮质神经元）的兴奋性来促进皮质-皮质通信。我将用四种互补的方法系统地检验他最近的假设。首先，我将描述内源性和诱发伽马对清醒小鼠初级体感皮层（SI）第V层细胞活性的影响（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（伽马对区域间增益的影响）的调制。第三，我将确定SI γ是否促进了MI中接受 来自SI的输入。第四，我将研究行为的影响，诱发SI伽马的感觉检测任务，涉及SI到MI通信，并试图模仿直接层V细胞去极化（伽马的行为增益的影响）SI伽马的影响。这些结果将提高我们对新皮层基本通讯的理解，但也应该作为伽马在大脑中假设行为的重要直接测试。

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.