The connectivity diagram of neocortical circuits is still unknown, and there are conflicting data as to whether cortical neurons are wired specifically or not. To investigate the basic structure of cortical microcircuits, we use a two-photon photostimulation technique that enables the systematic mapping of synaptic connections with single-cell resolution. We map the inhibitory connectivity between upper layers somatostatin-positive GABAergic interneurons and pyramidal cells in mouse frontal cortex. Most, and sometimes all, inhibitory neurons are locally connected to every sampled pyramidal cell. This dense inhibitory connectivity is found at both young and mature developmental ages. Inhibitory innervation of neighboring pyramidal cells is similar, regardless of whether they are connected among themselves or not. We conclude that local inhibitory connectivity is promiscuous, does not form subnetworks, and can approach the theoretical limit of a completely connected synaptic matrix.
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