Specific Hippocampal Interneurons Shape Consolidation of Recognition Memory

• Published in: Cell reports (Cambridge) Vol. 32; no. 7; p. 108046
• Main Authors: Oliveira da Cruz, Jose F., Busquets-Garcia, Arnau, Zhao, Zhe, Varilh, Marjorie, Lavanco, Gianluca, Bellocchio, Luigi, Robin, Laurie, Cannich, Astrid, Julio-Kalajzić, Francisca, Lesté-Lasserre, Thierry, Maître, Marlène, Drago, Filippo, Marsicano, Giovanni, Soria-Gómez, Edgar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.08.2020; Cell Press
• Subjects: CB1 receptor; D1 receptor; dopamine; endocannabinoid system; GABA; hippocampus; interneurons; Life Sciences; long-term potentiation; novel object recognition memory; hippocampus; D1 receptor; CB1 receptor; novel object recognition memory; GABA; endocannabinoid system; dopamine; interneurons; long-term potentiation; D receptor; CB receptor
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108046

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. [Display omitted] •CB1Rs are present in hippocampal D1R-positive interneurons•CB1R/D1R-positive interneurons control the late phase of recognition memory•CB1R/D1R-positive interneurons control learning-induced facilitation of LTP Oliveira da Cruz et al. show that a specific subpopulation of hippocampal CB1 and D1 receptor-positive neurons controls late consolidation of recognition memory and associated synaptic plasticity by moderating local inhibitory GABAergic activity in the hippocampus.