DESCRIPTION (provided by applicant): The function of the nervous system is dependent on complex interactions between networks of neurons composed of multiple neuron types. Understanding how these networks function both in health and disease is dependent on understanding the precise connectivity between specific neurons types and their functional interactions in the intact brain. It is therefore apparent that, in order to have an adequate understanding of the nervous system, it is necessary to have detailed descriptions of neuronal connectivity with the same level of precision at which these systems operate and to selectively manipulate and measure the activity of specific cell types in the context of the normal functioning network. The research proposed here is aimed at revealing the detailed connectivity and function of specific types of inhibitory cortical neurons. Intersectional genetic methods and Cre- and Flp-driver mouse lines are used to target gene expression to specific subsets of VIP positive inhibitory cortical neurons. The direct synaptic inputs and outputs of these neurons are then determined by monosynaptic rabies tracing or by optogenetic activation and whole cell recordings in brain slices. These same cell types will be optogenetically activated in vivo to assess their impact on other cells in the intact network and in the generation of sensory receptive fields. These experiments are designed to test hypotheses about the interactions between specific neural elements and their contributions to perception, cognition, and behavior.