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bioRxiv · 10.1101/842021

Specific hippocampal interneurons shape consolidation of recognition memory

Oliveira da Cruz, J. F.·Busquets-Garcia, A.·Zhao, Z.·Varilh, M.·Lavanco, G.·Bellocchio, L.·Robin, L.·Cannich, A.·Julio-Kalajzic, F.·Drago, F.·Marsicano, G.·Soria-Gomez, E.
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Abstract

A complex array of different inhibitory interneurons tightly controls hippocampal activity, but how such diversity specifically impacts on memory processes is scantly known. We found that a small subclass of type-1 cannabinoid receptor (CB1)-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D1 receptor signaling to GABAergic transmission. Mice lacking CB1 in D1-positive cells (D1-CB1-KO) displayed impaired long-term, but not short-term, object recognition memory. Re-expression of CB1 in hippocampal, but not striatal, D1-positive cells rescued this memory impairment. Learning induced a facilitation of in vivo hippocampal long-term potentiation (LTP), which was abolished in mutant mice. Chemogenetic and pharmacological experiments revealed that both CB1-mediated memory and associated LTP facilitation involves the local control of GABAergic inhibition in a D1-dependent manner. This study reveals that CB1-/D1-expressing interneurons shape hippocampal circuits to sustain recognition memory, thereby identifying a mechanism linking the diversity of hippocampal interneurons to specific behavioral and cognitive outcomes.

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Oliveira da Cruz, J. F., Busquets-Garcia, A., Zhao, Z., Varilh, M., Lavanco, G., Bellocchio, L., Robin, L., Cannich, A., Julio-Kalajzic, F., Drago, F., Marsicano, G., Soria-Gomez, E.. 2019-11-14. Specific hippocampal interneurons shape consolidation of recognition memory. https://doi.org/10.1101/842021

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