Dentate gyrus network regulation by somatostatin- and parvalbumin-expressing interneurons differentially impacts...

GABAergic interneurons regulate circuit dynamics of memory-processing brain structures. However, the role of the dentate gyrus (DG) and its predominant interneuron subtypes - somatostatin-expressing (SST+) and parvalbumin-expressing (PV+) - in different stages of memory processing is unknown. We tested how the chemogenetic manipulation of DG SST+ and PV+ interneurons in mice influences encoding, consolidation, and retrieval of hippocampus-dependent object-location memory (OLM). The activation of DG SST+ interneurons impairs OLM encoding and retrieval, dramatically suppresses DG granule cell activity, and (during encoding) suppresses downstream CA1 network activity. Granule cell inhibition predicts OLM deficits in individual mice. In striking contrast, PV+ interneuron activation selectively disrupts encoding, but not retrieval, of OLM, and minimally impacts DG or downstream hippocampal activity. Thus, the regulation of the DG network by SST+ and PV+ interneurons differentially contributes to the various stages of spatial memory processing, suggesting that distinct network mechanisms are engaged in the hippocampus during each processing stage.