Specific Hippocampal Interneurons Shape Consolidation of Recognition Memory

A complex array of inhibitory interneurons tightly controls hippocampal activity, but how such diversity specifically affects memory processes is not well understood. We find that a small subclass of type 1 cannabinoid receptor (CB1R)-expressing hippocampal intemeurons determines episodic-like memory consolidation by linking dopamine D-1 receptor (D1R) signaling to GABAergic transmission. Mice lacking CB(1)Rs in D-1-positive cells (D-1-CB1-KO) display impairment in long-term, but not short-term, novel object recognition memory (NOR). Re-expression of CB(1)Rs in hippocampal D1R-positive cells rescues this NOR deficit. Learning induces an enhancement of in vivo hippocampal long-term potentiation (LTP), which is absent in mutant mice. CB1R-mediated NOR and the associated LTP facilitation involve local control of GABAergic inhibition in a D-1-dependent manner. This study reveals that hippocampal CB1R-/D1R-expressing interneurons control NOR memory, identifying a mechanism linking the diversity of hippocampal interneurons to specific behavioral outcomes.