Author/Authors :
Jing Han، نويسنده , , Philip Kesner، نويسنده , , Mathilde Metna-Laurent، نويسنده , , Tingting Duan، نويسنده , , Lin Xu، نويسنده , , Francois Georges، نويسنده , , Muriel Koehl، نويسنده , , Djoher Nora Abrous، نويسنده , , Juan Mendizabal-Zubiaga، نويسنده , , Pedro Grandes، نويسنده , , Qingsong Liu، نويسنده , , Guang Bai، نويسنده , , Wei Wang، نويسنده , , Lize Xiong، نويسنده , , Wei Ren، نويسنده , , Giovanni Marsicano، نويسنده , , Xia Zhang، نويسنده ,
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 (CB1R) in brain astroglial cells but is conserved in mice lacking CB1R 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 CB1R and is associated with astroglia-dependent hippocampal LTD in vivo.
