Project Summary: GABAergic interneurons are central to the normal development and function of neocortical circuits. In particular, cells that express the peptide somatostatin (SST-INs) are thought to play critical roles in both spontaneous and sensory-evoked neuronal activity, primarily via their robust inhibition of the dendrites of excitatory pyramidal neurons. However, the functional roles of the diverse classes of SST-INs in deep cortical layers remain unknown. Furthermore, whereas the role of SST-INs in superficial cortical layers of adult animals has been well characterized, their function in the infragranular layers is unknown. Our preliminary data suggest the properties of SST-Ins vary across different cortical layers and thus may serve different roles. To further explore this observation, we propose to combine a number of methodological approaches, including optogenetic manipulations, 2-photon and viral tracing. We will test the following hypotheses: (1) SST-IN populations in superficial and deep layers of visual cortex have distinct responses and differentially regulated by behavioral state due to differences in presynaptic inputs. (2) SST-IN populations are functionally distinct across the layers and differ in their impact on sensory processing. Our results will provide an unprecedented level of insight into the function of SST-INs and their relationship to visual processing in the neocortex.