SOMA-LOCATION OF PARVALBUMIN-EXPRESSING INTERNEURONS DEFINES THEIR CONTRIBUTION TO FEEDFORWARD AND FEEDBACK INHIBITION

Fast-spiking parvalbumin-expressing interneurons (PVIs) provide strong perisomatic-inhibition to granule cells (GCs) in the dentate gyrus (DG). They can be recruited by perforant path inputs onto their apical dendrites from the entorhinal cortex, delivering feedforward inhibition or by GCs onto their basal dendrites mediating feedback inhibition. The current view is that both forms of inhibition are inseparable in PVIs, and difficult to functionally discriminate in behavioral paradigms. By combining in vitro whole-cell patch-clamp recordings, in vivo single-unit recordings of optogenetically identified PVIs, and network modeling, here we provide evidence that DG PVIs can be subdivided into two functional subgroups on the basis of their soma location. PVI_outers, with somata at or above the outer granule cell layer (gcl) –molecular layer (ml) border, are preferentially recruited by perforant path inputs, providing short latency uniform feedforward inhibition to GCs. In contrast, PVI_inners, with somata at the inner gcl –hilar border, are more effectively recruited by GCs, based on stronger synaptic plasticity and higher GC input connectivity, preferentially providing delayed, reliable and dynamic feedback inhibition. In vivo recordings further revealed that activity of PVI subtypes differentially relate to dentate spikes, with PVI_outers being active during the first half and PVI_inners preferentially discharging during the second half of dentate spike events. Finally, computational analysis suggests that the temporal sequence of feedforward and feedback inhibition, provided by these two PVI subgroups, supports pattern separation processes by winner-takes-all mechanisms. Thus, partial uncoupling of both forms of inhibition may enhance PVIs dynamical range during network computations.