Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

Jing Han 1 Philip Kesner Mathilde Metna-Laurent Tingting Duan Lin Xu 2 Francois Georges 3 Muriel Koehl 4 Djoher Nora Abrous 5 Juan Mendizabal-Zubiaga Pedro Grandes Qingsong Liu 6 Guang Bai 7 Wei Wang Lize Xiong 8 Wei Ren 9 Giovanni Marsicano 5 Xia Zhang 10
1 IRENAV - Institut de Recherche de l'Ecole Navale (EA 3634)
2 Key Laboratory of Animal Models and Human Disease Mechanisms
3 IINS - Interdisciplinary Institute for Neuroscience
4 MAP - Modèles et simulation pour l'architecture, l'urbanisme et le paysage
5 Physiopathologie du système nerveux central - Institut François Magendie
6 U1007 - Homéostasie cellulaire et cancer - Reprogrammation des réponses biologiques et thérapies alternatives
7 ONERA - The French Aerospace Lab [Châtillon]
8 Laboratory of Learning and Memory
9 Shanghai Key Laboratory of Trustworthy Computing
10 IDAEA - Institute of Environmental Assessment and Water Research
Abstract : Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo.
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https://hal.archives-ouvertes.fr/hal-01160047
Contributeur : Francois Georges <>
Soumis le : jeudi 4 juin 2015 - 12:48:30
Dernière modification le : mercredi 7 août 2019 - 11:46:02

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CNRS | INSA-STRASBOURG | UNIV-PARIS5 | USPC | MAP | SITE-ALSACE | ONERA | INSA-GROUPE

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Jing Han, Philip Kesner, Mathilde Metna-Laurent, Tingting Duan, Lin Xu, et al.. Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.. Cell, Elsevier, 2012, 148 (5), pp.1039-50. ⟨10.1016/j.cell.2012.01.037⟩. ⟨hal-01160047⟩

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