The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission

被引：363

作者：

Tanimura, Asami ^{[1
]}

Yamazaki, Maya ^{[3
]}

Hashimotodani, Yuki ^{[1
]}

Uchigashima, Motokazu ^{[4
]}

Kawata, Shinya ^{[1
]}

Abe, Manabu ^{[3
]}

Kita, Yoshihiro ^{[2
]}

Hashimoto, Kouichi ^{[1
,5
]}

Shimizu, Takao ^{[2
]}

Watanabe, Masahiko ^{[4
]}

Sakimura, Kenji ^{[3
]}

Kano, Masanobu ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Neurophysiol, Tokyo 1130033, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Biochem & Mol Biol, Tokyo 1130033, Japan

[3] Niigata Univ, Dept Cellular Neurobiol, Brain Res Inst, Niigata 9518585, Japan

[4] Hokkaido Univ, Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan

[5] Japan Sci & Technol Agcy, CREST, PRESTO, Kawaguchi, Saitama 3320012, Japan

来源：

NEURON | 2010年 / 65卷 / 03期

关键词：

METABOTROPIC GLUTAMATE RECEPTORS; CANNABINOID CB1 RECEPTOR; ENDOGENOUS CANNABINOIDS; PRESYNAPTIC INHIBITION; HIPPOCAMPAL SYNAPSES; GABA RELEASE; BRAIN; SYSTEM; DEPOLARIZATION; ACTIVATION;

D O I：

10.1016/j.neuron.2010.01.021

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase alpha (DGL alpha) and beta (DGL beta). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGL alpha knockout mice, whereas the retrograde suppression was intact in DGL beta knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGL alpha knockout brains, whereas the 2-AG content was normal in DGL beta knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGL alpha, but not by DGL beta, mediates retrograde suppression at central synapses.

引用

页码：320 / 327

页数：8

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