Acute Cannabinoids Impair Working Memory through Astroglial CB1 Receptor Modulation of Hippocampal LTD

被引：375

作者：

Han, Jing ^{[3
]}

Kesner, Philip ^{[4
,5
]}

Metna-Laurent, Mathilde ^{[1
,2
]}

Duan, Tingting ^{[6
,7
]}

Xu, Lin ^{[6
]}

Georges, Francois ^{[2
,8
]}

Koehl, Muriel ^{[1
,2
]}

Abrous, Djoher Nora ^{[1
,2
]}

Mendizabal-Zubiaga, Juan ^{[9
]}

Grandes, Pedro ^{[9
]}

Liu, Qingsong ^{[10
]}

Bai, Guang ^{[11
]}

Wang, Wei ^{[12
]}

Xiong, Lize ^{[13
]}

Ren, Wei ^{[3
]}

Marsicano, Giovanni ^{[1
,2
]}

Zhang, Xia ^{[4
,5
]}

机构：

[1] INSERM, F-33000 Bordeaux, France

[2] Univ Bordeaux, U862, F-33000 Bordeaux, France

[3] Shaanxi Normal Univ, Coll Life Sci, Xian 710062, Peoples R China

[4] Univ Ottawa, Inst Mental Hlth Res Royal, Dept Psychiat, Ottawa, ON K1Z 7K4, Canada

[5] Univ Ottawa, Inst Mental Hlth Res Royal, Dept Cellular & Mol Med, Ottawa, ON K1Z 7K4, Canada

[6] Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Peoples R China

[7] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China

[8] CNRS, Interdisciplinary Inst Neurosci, UMR 5297, F-33000 Bordeaux, France

[9] Univ Basque Country, Fac Med & Dent, Dept Neurosci, Leioa 48940, Spain

[10] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA

[11] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Program Neurosci, Baltimore, MD 21201 USA

[12] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Neurol, Wuhan 430030, Hubai, Peoples R China

[13] Fourth Mil Med Univ, Xijing Hosp, Dept Anesthesiol, Xian 710032, Peoples R China

来源：

CELL | 2012年 / 148卷 / 05期

基金：

国家高技术研究发展计划(863计划); 欧洲研究理事会; 加拿大自然科学与工程研究理事会; 加拿大健康研究院; 中国国家自然科学基金;

关键词：

LONG-TERM DEPRESSION; SYNAPTIC-TRANSMISSION; SPATIAL MEMORY; ENDOCANNABINOID SYSTEM; CA1; REGION; LOCALIZATION; POTENTIATION; PERFORMANCE; EXPRESSION; PLASTICITY;

D O I：

10.1016/j.cell.2012.01.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1039 / 1050

页数：12

共 69 条

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