Abstract
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.
Highlights
The dentate gyrus contains neural stem cells that continually generate new glutamatergic neurons, the granule cells (GCs), throughout life
In contrast to Parvalbumin-expressing interneurons (PVs)-evoked GABAA postsynaptic currents (GPSCs), NO711 (5 mM) increased the amplitude and rise time of GPSCs in both newborn and mature GCs (Figure 3D). These results show that optogenetic stimulation of neuronal nitric oxide synthase (nNOS)-expressing interneurons generate GPSCs consistent with volume transmission from neurogliaform interneurons, and that slow GPSCs in newborn GCs from both PV and nNOS interneurons are generated by a spatial-temporal [GABA] profile that differs from typical mature PV synapses
As expected for pooling from multiple release sites, the decay of GPSCs evoked by single PVs had faster kinetics than GPSCs evoked by light stimulation (Figure 6C, inset). Together these results show that single PVs can generate GPSCs in newborn GCs, but suggest that optogenetic stimulation generates GABA pooling from many active PVs
Summary
The dentate gyrus contains neural stem cells that continually generate new glutamatergic neurons, the granule cells (GCs), throughout life. Parvalbumin-expressing interneurons (PVs) are important mediators of activity-dependent regulation, since optogenetic manipulation of PVs alters stem cell quiescence and progenitor proliferation, as well as newborn GC survival and maturation (Song et al, 2012; Song et al, 2013; Alvarez et al, 2016). In light of the important role of PVs in regulating early events in the neurogenic cascade, we sought to understand the mechanisms underlying slow GABAA receptor signaling from PVs to newborn GCs. One possibility is that PVs innervate newly-generated GCs, but new synapses undergo a maturational process prior to supporting fast transmission (Song et al, 2013; Groisman et al, 2020).
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