Gothard, G.; Mahfooz, K.; Newey, S. E.; Tinelli, S.; Buchan, M. J.; Burman, R. J.; Akerman, C. J.

The degree to which cortical neurons share inhibitory synaptic input determines their co-activity within a network. However, the principles by which inhibition is shared between neurons are not known. Here we combine in utero labeling with in vivo two-photon targeted patch-clamp recordings in mature cortex to reveal that a layer 2/3 (L2/3) pyramidal neuron's local inhibitory input reflects the embryonic progenitor type from which the neuron is born. In contrast to neighboring neurons, pyramidal neurons derived from intermediate progenitors receive synaptic inhibition that is weakly coupled to local network activity. The underlying mechanisms do not depend upon the amount of inhibitory input received from different interneuron subclasses. Rather, progenitor type defines how much inhibitory input a neuron shares with its neighbors, which is reflected in how individual interneurons target pyramidal neurons according to progenitor type. These findings reveal new significance for progenitor diversity and identify ontogenetic origins of fine-scale inhibitory cortical subnetworks.