Somatostatin Interneurons Recruit Pre- and Postsynaptic GABA_B Receptors in the Adult Mouse Dentate Gyrus

The integration of spatial information in the mammalian dentate gyrus (DG) is critical to navigation. Indeed, DG granule cells (DGCs) rely upon finely balanced inhibitory neurotransmission in order to respond appropriately to specific spatial inputs. This inhibition arises from a heterogeneous population of local GABAergic interneurons (INs) that activate both fast, ionotropic GABA_A receptors (GABA_AR) and slow, metabotropic GABA_B receptors (GABA_BR), respectively. GABA_BRs in turn inhibit pre- and postsynaptic neuronal compartments via temporally long-lasting G-protein-dependent mechanisms. The relative contribution of each IN subtype to network level GABA_BR signal setting remains unknown. However, within the DG, the somatostatin (SSt) expressing IN subtype is considered crucial in coordinating appropriate feedback inhibition on to DGCs. Therefore, we virally delivered channelrhodopsin 2 to the DG in order to obtain control of this specific SSt IN subpopulation in male and female adult mice. Using a combination of optogenetic activation and pharmacology, we show that SSt INs strongly recruit postsynaptic GABA_BRs to drive greater inhibition in DGCs than GABA_ARs at physiological membrane potentials. Furthermore, we show that in the adult mouse DG, postsynaptic GABA_BR signaling is predominantly regulated by neuronal GABA uptake and less so by astrocytic mechanisms. Finally, we confirm that activation of SSt INs can also recruit presynaptic GABA_BRs, as has been shown in neocortical circuits. Together, these data reveal that GABA_BR signaling allows SSt INs to control DG activity and may constitute a key mechanism for gating spatial information flow within hippocampal circuits.