Soma location of parvalbumin-expressing interneurons defines their contribution to feedforward and feedback inhibition

Feedforward and feedback inhibition are two elementary interrelated processes that are integrated in cortical microcircuits. Using in vitro whole-cell recordings of parvalbumin-expressing interneurons (PVIs) in the mouse dentate gyrus (DG), we provide first evidence that the soma location of PVIs defines their preference for providing feedforward or feedback inhibition to the network. PVIs with somata at the outer border of the granule cell to molecular layer (PVI_outers) are more strongly recruited by afferent entorhinal cortex inputs, providing short-latency uniform feedforward inhibition to granule cells as compared to PVIs with soma location at the inner granule cell layer to hilar border (PVI_inners). In contrast, PVI_inners are more strongly recruited by granule cells than PVI_outers due to their stronger synaptic plasticity and higher input connectivity, preferentially providing a delayed, reliable feedback inhibition to the DG network. In vivo single-unit recordings of optogenetically identified PVIs revealed that activity of both subtypes differentially relate to dentate spikes, with PVI_outers being predominantly active during the first half and PVI_inners preferentially discharging during the second half of dentate spikes. Our data-driven computational model provides an explanation on how the functional integration of both PVI subtypes in the DG network support pattern separation processes by promoting winner-takes-all mechanisms.