Specific Hippocampal Interneurons Shape Consolidation of Recognition Memory

Abstract

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 interneurons determines episodic-like memory consolidation by linking dopamine D₁ receptor (D₁R) signaling to GABAergic transmission. Mice lacking CB₁Rs in D₁-positive cells (D₁-CB₁-KO) display impairment in long-term, but not short-term, novel object recognition memory (NOR). Re-expression of CB₁Rs 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 D₁-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.