Feedforward and disinhibitory circuits differentially control activity of cortical somatostatin interneurons during behavioral state transitions.

Interneurons (INs), specifically those in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-INs, are strongly modulated by the behavioral context. Yet, the mechanisms by which these INs are recruited during active states and whether their activity is consistent across sensory cortices remain unclear. We now report that in mice, locomotor activity strongly recruits SST-INs in the primary somatosensory (S1) but not the visual (V1) cortex. This diverse engagement of SST-INs cannot be explained by differences in VIP-IN function but is absent in the presence of visual input, suggesting the involvement of feedforward sensory pathways. Accordingly, inactivating the somatosensory thalamus, but not decreasing VIP-IN activity, significantly reduces the modulation of SST-INs by locomotion. Model simulations suggest that the differences in SST-INs across behavioral states can be explained by varying ratios of VIP- and thalamus-driven activity. By integrating feedforward activity with neuromodulation, SST-INs are anticipated to be crucial for adapting sensory processing to behavioral states.