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Control of neural circuit function by the endocannabinoid 2-arachidonoylglycerol

開催日 2014/9/12
時間 15:00 - 17:00
会場 Room F(302)
Chairperson(s) 狩野 方伸 / Masanobu Kano (東京大学大学院医学系研究科 神経生理学分野 / Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Japan)
渡辺 雅彦 / Masahiko Watanabe (北海道大学大学院医学研究科 解剖学講座 解剖発生学分野 / Department of Anatomy, Hokkaido University Graduate School of Medicine, Japan)

Modulation of synaptic transmission by 2-arachidonoylglycerol and its metabolites

  • S2-F-2-3
  • 少作 隆子 / Takako Ohno-Shosaku:1 狩野 方伸 / Masanobu Kano:2 
  • 1:金沢大院・保健・リハビリ / Fac Health Sci, Kanazawa Univ, Kanazawa, Japan 2:東京大院・医・神経生理 / Dept Neurophysiol, Grad Sch of Med, Univ of Tokyo, Tokyo, Japan 

2-Arachidonoylglycerol (2-AG), one of the two major endocannabinoids, functions as a retrograde messenger, and modulates synaptic transmission at various excitatory and inhibitory synapses throughout the brain. 2-AG is synthesized on demand and released from postsynaptic neurons, activates presynaptic CB1 cannabinoid receptors, and suppresses transmitter release transiently or persistently. 2-AG synthesis is induced by Ca2+ elevation and/or activation of Gq/11-coupled receptors, such as group I metabotropic glutamate receptors and M1/M3 muscarinic receptors. The final step of 2-AG synthesis is catalyzed by diacylglycerol lipase α (DGLα), which converts diacylglycerol to 2-AG. Monoacylglycerol lipase facilitates termination of the retrograde signal by hydrolyzing 2-AG. Although considerable progress has been made in elucidating the mechanisms, several questions remain unsolved. In the first part of this presentation, we summarize our studies with cultured hippocampal neurons, and present our current understanding of the molecular mechanisms of 2-AG-mediated retrograde signaling. In the latter half, we report our recent study, which suggests the possibility that 2-AG has a dual action on synaptic transmission and neuronal excitability, one being inhibitory and CB1-dependent (the aforementioned action) and the other being excitatory and CB1-independent. We used cultured hippocampal neurons, and examined effects of 2-AG application on spontaneous synaptic currents under the blockade of CB1/CB2 receptors and DGL. We found that 2-AG application increased the frequency of synaptic currents. This excitatory effect of 2-AG was suppressed by inhibition of MGL, suggesting the involvement of 2-AG metabolites. This excitatory action of 2-AG is just beginning to be addressed, and further studies are needed to clarify the molecular mechanisms. A full understanding of this action may shed some valuable light on physiological roles of 2-AG signaling.

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