Axo-dendritic overlap and laminar projection can explain interneuron connectivity to pyramidal cells.

Neocortical GABAergic interneurons have important roles in the normal and pathological states of the circuit. Recent work has revealed that somatostatin-positive (SOM) and parvalbumin-positive (PV) interneurons connect promiscuously to pyramidal cells (PCs). We investigated whether Peters' rule, that is, the spatial overlap of axons and dendrites, could explain this unspecific connectivity. We reconstructed the morphologies of P11-17 mouse SOM and PV interneurons and their PC targets, and performed Monte Carlo simulations to build maps of predicted connectivity based on Peters' rule. We then compared the predicted with the real connectivity maps, measured with 2-photon uncaging experiments, and found no statistical differences between them in the probability of connection as a function of distance and in the spatial structure of the maps. Finally, using reconstructions of connected SOM-PCs and PV-PCs, we investigated the subcellular targeting specificity, by analyzing the postsynaptic position of the contacts, and found that their spatial distributions match the distribution of postsynaptic PC surface area, in agreement with Peters' rule. Thus, the spatial profile of the connectivity maps and even the postsynaptic position of interneuron contacts could result from the mere overlap of axonal and dendritic arborizations and their laminar projections patterns.