Paracrine Role for Somatostatin Interneurons in the Assembly of Perisomatic Inhibitory Synapses
Jianmin Su, Danielle Basso, Shivani Iyer, Kaiwen Su, Jessica Wei, Michael A. Fox
Abstract
GABAergic interneurons represent a heterogenous group of cell types in neocortex that can be clustered based on developmental origin, morphology, physiology, and connectivity. Two abundant populations of cortical GABAergic interneurons include the low-threshold, somatostatin (SST)-expressing cells and the fast-spiking, parvalbumin (PV)-expressing cells. While SST 1 and PV 1 interneurons are both early born and migrate into the developing neocortex at similar times, SST 1 cells are incorporated into functional circuits prior to PV 1 cells. During this early period of neural development, SST 1 cells play critical roles in the assembly and maturation of other cortical circuits; however, the mechanisms underlying this process remain poorly understood. Here, using both sexes of conditional mutant mice, we discovered that SST 1 interneuron-derived Collagen XIX, a synaptogenic extracellular matrix protein, is required for the formation of GABAergic, perisomatic synapses by PV 1 cells. These results, therefore, identify a paracrine mechanism by which early-born SST 1 cells orchestrate inhibitory circuit formation in the developing neocortex.