Project Summary The cortical column is a fundamental unit of processing in the cerebral cortex. Within each column are subnetworks of interconnected excitatory and inhibitory neurons, and this structure is repeated across the cortical processing hierarchy. We propose that inhibitory interneurons, through specialized circuits that can result in both inhibition and disinhibition of pyramidal neuron firing, are crucial aspects of specialized processing in cortical circuits across the processing hierarchy. To understand the roles of inhibition and disinhibition in cortical processing, the patterns interaction among cell types must be related to the functional properties of the local population. Primary auditory cortex (A1) and posterior parietal cortex (PPC) are situated at different levels of the processing hierarchy. In the proposed experiments, we will compare the functional logic of excitatory and inhibitory microcircuits in A1 and PPC, to determine the properties of local network organization that generalize and specialize across sensory and association cortex. In aim 1, we will compare the spatial and functional structure of excitatory impacts on local populations in A1 and PPC, by combining single cell optogenetic stimulation with two-photon calcium imaging in mice performing an auditory localization task. In aim 2, we will determine the spatial and functional properties of local inhibitory and disinhibitory motifs, by mapping the influence of individual inhibitory neurons on the local population. In aim 3, we will explore more natural stimulation patterns and their effects on cell-type-specific interactions. Together, these experiments will reveal the computational roles of specific cell types in local circuits, and establish the similarities and differences in the functional microcircuitry of sensory and association cortex.