Top-down modulation of sensory processing allows the animal to select inputs most relevant to current tasks. We found that the cingulate (Cg) region of mouse frontal cortex powerfully influences sensory processing in primary visual cortex (V1) through long-range projections that activate local GABAergic circuits. Optogenetic activation of Cg neurons enhanced V1 neuron responses and improved visual discrimination. Focal activation of Cg axons in V1 caused a response increase at the activation site but decrease at nearby locations (center-surround modulation). While somatostatin-positive GABAergic interneurons contributed preferentially to surround suppression, vasoactive intestinal peptide-positive interneurons were crucial for center facilitation. Long-range cortico-cortical projections thus act through local microcircuits to exert spatially specific top-down modulation of sensory processing.
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