Dopamine D2 Receptors modulate hippocampal theta rhythm through somatostatin interneurons

Abstract Spatiomolecular mapping of hippocampal dopamine receptor D2 (D2R) neurons revealed that in addition to hilar mossy cells, hippocampal SST-INs and, to a lesser extent, PV-INs expressed D2R. However, while the role of D2R signaling onto mossy cells has been characterized, the consequence of D2R activation onto hippocampal SST-INs and PV-INs is unknown. By combining pharmacological approaches and patch-clamp recordings in organotypic hippocampal slices from control or mice lacking Drd2 selectively in SST-INs and PV-INs, we found that D2R activation increase excitability in SST-INs while it decreases in PV-INs. These D2R-mediated changes rely on distinct intracellular pathways, involving the non-canonical β- arrestin-dependent pathway in SST-INs and the G protein-dependent pathway in PV-INs. Finally, our study also unveiled that D2R activation modulates theta oscillations through SST- INs D2R signaling.