Abstract
Fast-spiking parvalbumin-expressing interneurons (PVIs) and granule cells (GCs) of the dentate gyrus receive layer-specific dendritic inhibition. Its impact on PVI and GC excitability is, however, unknown. By applying whole-cell recordings, GABA uncaging and single-cell-modeling, we show that proximal dendritic inhibition in PVIs is less efficient in lowering perforant path-mediated subthreshold depolarization than distal inhibition but both are highly efficient in silencing PVIs. These inhibitory effects can be explained by proximal shunting and distal strong hyperpolarizing inhibition. In contrast, GC proximal but not distal inhibition is the primary regulator of their excitability and recruitment. In GCs inhibition is hyperpolarizing along the entire somato-dendritic axis with similar strength. Thus, dendritic inhibition differentially controls input-output transformations in PVIs and GCs. Dendritic inhibition in PVIs is suited to balance PVI discharges in dependence on global network activity thereby providing strong and tuned perisomatic inhibition that contributes to the sparse representation of information in GC assemblies.
Highlights
Fast-spiking parvalbumin-expressing interneurons (PVIs) and granule cells (GCs) of the dentate gyrus receive layer-specific dendritic inhibition
In this study we asked: how does location, amplitude and timing of dendritic inhibition control excitatory input strength and action potential generation in PVIs compared to GCs in the dentate gyrus? By combining experimental and computational approaches, we show that in PVIs, off-path distal inhibition is more efficient than on-path proximal inhibition in controlling the amplitude of subthreshold excitatory postsynaptic signals (EPSPs) and capable of silencing PVIs
To evaluate effects of dendritic filtering on the measured GGABA, we studied the propagation of inhibitory signals from their induction site to the soma using morphologically detailed computational models of PVIs and GCs21–23,54,55
Summary
Cell type-dependent on- and off-path inhibitory efficiency. The Opposite somato-dendritic EGABA gradients in PVIs and GCs. effect of dendritic inhibition on excitatory signals was examined What factors may underlie the different dendritic inhibitory. PVI models closely reproduced experimentally observed attenuations of dendritically evoked uncIPSCs under conditions of a linearly increasing somato-dendritic gradient of GGABA from 14 nS at the soma to ≥46 nS at distal dendrites (Fig. 5d, in vitro black vs model red and orange) This effect could not be reproduced by only changing the gradient of the somatodendritic Rm (Supplementary Fig. 7) or the axial resistance (Ra; Methods), supporting our conclusion that GGABA gradually increases along apical dendrites of PVIs, while it remains uniform at the somato-dendritic axis of GCs. EGABA and GGABA shape efficiency of dendritic inhibition. GC models equipped with a linear in vitrobased EGABA gradient (Fig. 6b) or a constant EGABA of −80 mV reproduced the experimentally obtained monotonic decline in inhibitory efficiency along the somato-dendritic axis of GCs (Fig. 6d, gray, blue and black, respectively), while deviations to more positive EGABA values (−60 or −70 mV) resulted in different IE spatial profiles (Fig. 6d, red and green vs black). The slower time course of synaptic signals in GCs supports input integration and the high efficiency of proximal inhibition
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