Differential Modulation of Dopamine D2 Receptor on Somatostatin and Parvalbumin Interneurons in the CA1 Area of the Dorsal Hippocampus

Abstract

Spatiomolecular mapping of hippocampal dopamine D2 receptor neurons revealed that in addition to hilar mossy cells, hippocampal somatostatin interneurons and, to a lesser extent, parvalbumin interneurons expressed dopamine D2 receptor. However, the consequence of dopamine D2 receptor activation on hippocampal somatostatin interneurons and parvalbumin interneurons is unknown. By combining pharmacological approaches and patch-clamp recordings in organotypic hippocampal slices from control mice or mice lacking Drd2 selectively in somatostatin or parvalbumin interneurons, we found that dopamine D2 receptor activation increases excitability in somatostatin interneurons while it decreases it in parvalbumin interneurons in the CA1 area. These changes depend on voltage-gated K channels and rely on distinct intracellular pathways, involving the non-canonical β-arrestin-dependent pathway in somatostatin interneurons and the G protein-dependent pathway in parvalbumin interneurons. Finally, our study unveils that activation of dopamine D2 receptor in somatostatin interneurons modulates methacholine-induced rhythmic synaptic activity at 4–15 Hz.