期刊
CELL
卷 148, 期 5, 页码 1039-1050出版社
CELL PRESS
DOI: 10.1016/j.cell.2012.01.037
关键词
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资金
- NIH [DA011322, DA024741, NS38077]
- Basque Country Government [GIC07/70-IT-432-07]
- Ministerio de Ciencia e Innovacion [SAF2009-07065]
- Red de Trastornos Adictivos, RETICS
- Instituto de Salud Carlos III
- MICINN [RD07/0001/2001]
- National Natural Science Foundation of China (NNSFC) [30725019, 81030021]
- National High Technology Research and Development Program of China (863) [2007AA02Z310]
- INSERM/Avenir
- INSERM
- European Research Council [ERC-2010-StG-260515]
- EU [HEALTH-F22008-223713]
- Fondation pour la Recherche Medicale
- Region Aquitaine
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Cheung Kong Scholar (Chang Jiang Scholar) Award
- Canadian Foundation for Innovation
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 alpha-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.
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