Feedforward circuits enable modality-specific control of cortical inhibition during behavioral state transitions

Abstract

SUMMARYActive behavior strongly influences sensory information processing in primary sensory cortices. Local interneurons, especially those involved in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-positive interneurons, play a crucial role in regulating cortical function during behavior. While numerous studies have focused on the recruitment of pyramidal neurons, the intricate network mechanisms governing the behavior-state-dependent modulation of inhibitory neurons remain unclear. Using intravital two-photon calcium imaging we have studied the neuronal pathways that regulate SST- and VIP-IN activity in sensory cortices during spontaneous behaviours. We now reveal that active behavioral states associated with increased locomotor activity strongly recruit L2/3 SST-INs in primary somatosensory (S1) but not visual (V1) cortex indicating modality-specific mechanisms control activity of cortical interneurons during active states. Such a difference between V1 and S1 disappears in the presence of visual sensory drive (ambient light) suggesting a critical involvement of feedforward sensory pathways in the positive modulation of SST-INs during spontaneous behaviors. In agreement, we now unveil that inactivating the somatosensory thalamus significantly reduces the recruitment of SST-INs in S1 by locomotion. In contrast, interfering with disinhibitory circuits via chemogenetic inactivation of VIP-INs further increased the sensitivity of SST-INs to variations in behavioural states. Our work thus reveals a previous unknown role for thalamic inputs in driving SST-INs, suggesting that by integrating feedforward activity with neuromodulation, SST-INs play a central role in adapting sensory processing to behavioral states in a sensory modality-specific manner.