Nonsynaptic GABA signaling in postnatal subventricular zone controls GFAP-expressing progenitor proliferation

In the postnatal subventricular zone (SVZ) local cues or signaling molecules released from neuroblasts limit the proliferation of glial fibrillary acidic protein (GFAP)-expressing progenitors thought to be stem cells. However, signals between SVZ cells have not been identified. We show that depolarizations of neuroblasts induce nonsynaptic SNARE-independent GABAA receptor currents in GFAP-expressing cells whose time-course depends on GABA uptake in acute mouse slices. We found that GABAA receptors are tonically activated in GFAP-expressing cells consistent with the presence of spontaneous depolarizations in neuroblasts that are sufficient to induce GABA release. These data demonstrate the existence of nonsynaptic GABAergic signaling between neuroblasts and GFAP-expressing cells. Furthermore, we show that GABAA receptor activation in GFAP-expressing cells limits their progression through the cell cycle. Thus, as GFAP-expressing cells generate neuroblasts, GABA released from neuroblasts provides a feedback mechanism to control the proliferation of GFAP-expressing progenitors by activating GABAA receptors.