VIP-to-SST cell circuit motif shows differential short-term plasticity across sensory areas of mouse cortex

Inhibition of GABAergic interneurons has been found to critically fine-tune the excitation-inhibition balance of the cortex. Inhibition is mediated by many connectivity motifs formed by GABAergic neurons. One such motif is the inhibition of somatostatin (SST)-expressing neurons by vasoactive intestinal polypeptide (VIP)-expressing neurons. We studied the synaptic properties of layer (L) 2/3 VIP cells onto L4 SST cells in somatosensory (S1) and visual (V1) cortices of mice of either sex using paired whole-cell patch clamp recordings, followed by morphological reconstructions. We identified strong differences in the morphological features of L4 SST cells, wherein cells in S1 fell into the non-Martinotti cell (nMC) subclass, while in V1 presented with Martinotti cell (MC)-like features. Around 40-45% of tested SST cells were inhibited by VIP cells in both cortices. While unitary connectivity properties of the VIP-to-nMC and VIP-to-MC motif were comparable, we observed stark differences in short-term plasticity. During high-frequency stimulation of both motifs, some connections showed short-term facilitation while others showed a stable response, with a fraction of VIP-to-nMC connections showing short-term depression. We thus provide evidence that VIP cells target morphological subclasses of SST cells differentially, forming cell-type specific inhibitory motifs. Significance statement Inhibitory circuits are involved in a wide variety of cortical computations. In particular, the inhibition of somatostatin-expressing (SST) neurons by vasoactive intestinal polypeptide- expressing (VIP) neurons has been well-documented in L2/3 of sensory cortices. It was recently identified that L4 SST neurons of S1 and V1 exhibit two different morphological subtypes, namely, non-Martinotti (nMC) cells in S1 and Martinotti (MC) cells in V1. We show that L2/3 VIP neurons inhibit both SST subtypes in L4 with similar dynamics. However, we also find that under high frequency stimulations, the VIP-to-nMC motif exhibits strong short-term depression, but this was not observed in VIP-to-MC motifs. Therefore, we identified morphologically distinct, inhibitory cell-type specific motifs in sensory cortices of mouse.