Cell Type and Circuit Mechanisms of Non-Invasive Brain Stimulation by Sensory Entrainment

The project will systematically investigate mechanisms of PSS by dissecting how cell types and circuit properties in the brain mediate the entrainment of neural activity and modifications of neuronal and non-neuronal cell populations. This involves systematic modeling efforts using highly detailed, bio-realistic models of mouse cortical circuits to simulate PSS effects at the level of a single cortical area (primary visual cortex) and the whole mouse cortex. Models of coupling from neuron activity to non-neuronal cells (e.g., microglia, vasculature) will also be developed. These modeling efforts will be combined with electrophysiology recordings in awake mice, accompanied by chronic and acute perturbations using chemogenetics and optogenetics. Modeling predictions regarding the roles of excitatory and inhibitory cell types in different cortical layers will be tested experimentally, and models will be refined. The project will also characterize transcriptomic and epigenetic responses to PSS in different cell types, correlating these with circuit effects.