![]() ![]() Apart from the classical basal spontaneous synaptic inhibition and afferent evoked feedforward and feedback inhibition, dentate granule cells (GCs) have been proposed to receive “sustained” increase in feedback synaptic inhibition following paired stimulation of perforant path (PP) inputs ( Larimer and Strowbridge, 2010). Dentate inhibition includes sustained tonic/extrasynaptic GABA currents as well as distinct phases of synaptic inhibition, which shape basal and afferent-evoked activity ( Stell et al., 2003 Ewell and Jones, 2010). The characteristically sparse dentate activity is maintained by the relatively hyperpolarized resting membrane potential and low input resistance of the projection neurons and their powerful inhibitory regulation ( Heinemann et al., 1992 Lothman et al., 1992). ![]() The hippocampal dentate gyrus is known for its uniquely sparse activity, essential for its function in pattern separation, a process of disambiguating similar inputs into distinct patterns of neural activity and memory representations ( Bekinschtein et al., 2013 GoodSmith et al., 2017). Since dentate GC activity levels during memory processing are heavily shaped by basal and feedback inhibition, the fundamental differences in basal and evoked sustained inhibition between SGCs and GCs characterized here provide a framework to reorganize current understanding of the dentate circuit processing. Notably, we demonstrate relatively lower activity-dependent increase in sustained feedback inhibitory synaptic inputs to SGCs when compared with GCs which would facilitate their persistent activity and preferential recruitment as part of memory ensembles. SIGNIFICANCE STATEMENT Our study identifies that feedback inhibitory regulation of dentate semilunar granule cells (SGCs), a sparse and functionally distinct class of projection neurons, differs from that of the classical projection neurons, GCs. The temporally selective blunting of activity-driven sustained inhibitory gating of SGCs could support their preferential and persistent recruitment during behavioral tasks. These results demonstrate that PV-INs, while contributing minimally to basal synaptic inhibition in both GCs and SGCs in slices, mediate sustained feedback inhibition selectively in SGCs. ![]() Optical suppression of PV-IN selectively reduced sustained IPSCs in SGCs but not in GCs. However, the robust increase in sustained polysynaptic IPSCs elicited by paired afferent stimulation was lower in SGCs than in simultaneously recorded GCs. Amplitude and kinetics of IPSCs evoked by perforant path (PP) activation were not different between GCs and SGCs. In studies conducted in hippocampal slices from mice, we find that although basal IPSCs are more frequent in SGCs and optical activation of PV-INs reliably elicited IPSCs in both GCs and SGCs, optical suppression of PV-INs failed to reduce IPSC frequency in either cell type. However, the contribution of PV-INs to basal and input-driven sustained synaptic inhibition in GCs and semilunar granule cells (SGCs), a sparse morphologically distinct dentate projection neuron subtype, is currently unknown. Strong inhibitory synaptic gating of dentate gyrus granule cells (GCs), attributed largely to fast-spiking parvalbumin interneurons (PV-INs), is essential to maintain sparse network activity needed for dentate dependent behaviors. ![]()
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