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 (CB(1)R)-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D(1) receptor (D(1)R) signaling to GABAergic transmission. Mice lacking CB(1)Rs in D(1)-positive cells (D(1)-CB(1)-KO) display impairment in long-term, but not short-term, novel object recognition memory (NOR). Re-expression of CB(1)Rs in hippocampal D(1)R-positive cells rescues this NOR deficit. Learning induces an enhancement of in vivo hippocampal long-term potentiation (LTP), which is absent in mutant mice. CB(1)R-mediated NOR and the associated LTP facilitation involve local control of GABAergic inhibition in a D(1)-dependent manner. This study reveals that hippocampal CB(1)R-/D(1)R-expressing interneurons control NOR memory, identifying a mechanism linking the diversity of hippocampal interneurons to specific behavioral outcomes.