Systematic Testing of a Neocortical Gamma Gain Hypothesis

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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.