Specific hippocampal interneurons shape consolidation of recognition memory

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 (CB 1 )-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D 1 receptor signaling to GABAergic transmission.Mice lacking CB 1 in D 1 -positive cells (D 1 -CB 1 -KO) displayed impaired long-term, but not short-term, object recognition memory. Re-expression of CB 1 in hippocampal, but not striatal, D 1 -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 CB 1 -mediated memory and associated LTP facilitation involves the local control of GABAergic inhibition in a D 1 -dependent manner.This study reveals that CB 1 -/D 1 -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.

Subcellular specificity of cannabinoid effects in striatonigral circuits

“…Mice that underwent behavioral experiments were fixed by transcardial perfusion of 4% PFA and their brain were processed for imaging (to detect BFLP and EGFP) and double fluorescent in-situ hybridization (see below), or for immunofluorescence as previously described(Hebert-Chatelain et al, 2016), with primary antibodies directed against CB 1 receptor (CB 1 -Go-Af450-1; 2 μg/ml; Frontier Science Co. Ltd), to detect CB 1 rescue and CB 1 deletion, or against HA-tag (#3724; Cell Signaling Technology Danvers, MA) to confirm overexpression of mt-sAC. Mice that did not fulfill histological positive criteria were excluded from the study.Double fluorescent in-situ hybridization coupled to GFP immunodetectionDouble FISH/GFP immunofluorescence experiments to measure the number of CB 1 /D 1 R vs CB 1 /D 2 R positive striatal neurons in the deletion experiments, were carried out as previously described(Oliveira da Cruz et al, 2020;Terral et al, 2019). Briefly, free-floating frozen coronal sections were cut out with a cryostat 30 (30 μm, Microm HM 500M Microm Microtech) and collected in an antifreeze solution and conserved at −20°C.…”

Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats

“…CB1Rs are mainly expressed on GABAergic neurons of the HPC [77] where they modulate synaptic plasticity and play a role in cognition [78]. Recent research using conditional knockout animals and chemogenetic approaches have dissociated discrete circuits and specific cell types expressing CB1Rs to explore underlying mechanisms involved in drugassociated memory [79][80][81]. In particular, depending on their cell-type localization, CB1Rs appear to differentially control cellular and molecular effects of cocaine, with CB1R expression in forebrain GABAergic neurons and cortical glutamatergic neurons controlling sensitivity to cocaine and associative learning, respectively [35].…”

Cannabinoid control of hippocampal functions: the where matters

“…In the dentate gyrus, exogenous cannabinoids acting on CB1 receptors present in GABAergic neurons could also result in a disruption of short-term memory [23]. In contrast, there is evidence that physiological activation of CB1 receptors in GABAergic neurons is essential for certain types of memory [20,35,36]. The inhibition produced by endocannabinoid signaling in hippocampal GABAergic neurons is necessary for complex learning processes such as incidental associations [35].…”