Parvalbumin-expressing interneurons (PVs) in the dentate gyrus provide activity-dependent regulation of adult neurogenesis as well as maintain inhibitory control of mature neurons. In mature neurons, PVs evoke GABAA postsynaptic currents (GPSCs) with fast rise and decay phases that allow precise control of spike timing, yet synaptic currents with fast kinetics do not appear in adult-born neurons until several weeks after cell birth. Here we used mouse hippocampal slices to address how PVs signal to newborn neurons prior to the appearance of fast GPSCs. Whereas PV-evoked currents in mature neurons exhibit hallmark fast rise and decay phases, newborn neurons display slow GPSCs with characteristics of spillover signaling. We also unmasked slow spillover currents in mature neurons in the absence of fast GPSCs. Our results suggest that PVs mediate slow spillover signaling in addition to conventional fast synaptic signaling, and that spillover transmission mediates activity-dependent regulation of early events in adult neurogenesis.

At individual synapses, the number of neurotransmitter-filled vesicles released dictates the reliability and temporal fidelity of synaptic transmission. It is widely accepted that the product of each vesicle's release probability solely determines whether multiple vesicles can be released simultaneously, but here we show that this assumption does not hold at two synapses. Synapsin-dependent regulation of the readily-released pool of vesicles determines the number of vesicles released per active zone independent of a vesicle's release probability, resolving long-standing questions about the mechanisms that control the number of vesicles released at each active zone.