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 _A R) and slow, metabotropic GABA _B receptors (GABA _B R), respectively. GABA _B Rs 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 _B R 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 _B Rs to drive greater inhibition in DGCs than GABA _A Rs at physiological membrane potentials. Furthermore, we show that in the adult mouse DG, postsynaptic GABA _B R 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 _B Rs, as has been shown in neocortical circuits. Together, these data reveal that GABA _B R signaling allows SSt INs to control DG activity and may constitute a key mechanism for gating spatial information flow within hippocampal circuits.
Competing Interests: The authors declare no competing financial interests.
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