A dendritic substrate for temporal diversity of cortical inhibition.

In the mammalian neocortex, GABAergic interneurons (INs) inhibit cortical networks in profoundly different ways. The extent to which this depends on how different INs process excitatory signals along their dendrites is poorly understood. Here, we reveal that the functional specialization of two major populations of cortical INs is determined by the unique association of different dendritic integration modes with distinct synaptic organization motifs. We found that somatostatin (SST)-INs exhibit NMDAR-dependent dendritic integration and uniform synapse density along the dendritic tree. In contrast, dendrites of parvalbumin (PV)-INs exhibit passive synaptic integration coupled with proximally enriched synaptic distributions. Theoretical analysis shows that these two dendritic configurations result in different strategies to optimize synaptic efficacy in thin dendritic structures. Yet, the two configurations lead to distinct temporal engagement of each IN during network activity. We confirmed these predictions with in vivo recordings of IN activity in the visual cortex of awake mice, revealing a rapid and linear recruitment of PV-INs as opposed to a long-lasting integrative activation of SST-INs. Our work reveals the existence of distinct dendritic strategies that confer distinct temporal representations for the two major classes of neocortical INs and thus dynamics of inhibition.

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.