Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Année : 2012

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

Résumé

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.

Dates et versions

hal-01160047 , version 1 (04-06-2015)

Identifiants

Citer

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, 2012, 148 (5), pp.1039-50. ⟨10.1016/j.cell.2012.01.037⟩. ⟨hal-01160047⟩
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