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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)

Unique molecular-anatomical organization of 2-AG-mediated retrograde signaling at CCK/VGluT3-expressing basket cell-pyramidal cell synapses

  • S2-F-2-2
  • 内ヶ島 基政 / Motokazu Uchigashima:1 渡辺 雅彦 / Masahiko Watanabe:1 
  • 1:北海道大院医解剖発生 / Dept Ant Hokkaido Univ Grad Sch Med, Sapporo, Japan 

Endocannabinoid 2-arachidonoyglycerol (2-AG) is produced by diacylglycerol lipase α (DGLα) in postsynaptic neurons, and acts on presynaptic cannabinoid CB1 receptor to suppress transmitter release. In general, CB1 is particularly enriched at inhibitory synapses formed by cholecystokinin (CCK)-positive basket cells than at excitatory synapses. In comparison, DGLα is highly accumulated at around excitatory synapses. Against the general scheme for reciprocal molecular allocation, we previously found a unique type of perisomatic synapses formed between CCK-positive basket cells and pyramidal cells in the basal nucleus of amygdala (BA). At this synapse, CB1 and DGLα were intensively accumulated on the apposed presynaptic and postsynaptic membranes, respectively, and 2-AG-mediated retrograde suppression was much readily induced at GABAergic synapses on BA pyramidal cells. We termed this "invaginating synapse", as the presynaptic terminal was specialized to form invagination into the soma. We further noticed that, although only 25% of CB1-expressing interneurons co-expressed vesicular glutamate transporter-3 (VGluT3), DGLα-positive perisomatic clusters on BA pyramidal cells were exclusively apposed to CB1+/CCK+/VGluT3+ terminals, but not to CB1+/CCK+/VGluT3- terminals. Interestingly, metabotroic glutamate receptor type 5 (mGluR5), a Gq/11-coupled receptor whose activation promotes 2-AG synthesis, was widely and richly distributed on BA pyramidal cells. Such a molecular configuration was also found at CB1+/CCK+/VGluT3+ synapses in the entorhinal and motor cortices. Our findings suggest that 2-AG-mediated signaling molecules are intensively arranged at CCK-positive/VGluT3-positive basket cell synapses on pyramidal cell in cortical regions, and that co-release of glutamate and CCK may potently facilitate 2-AG synthesis and thereby preferentially suppress perisomatic inhibition by CCK-positive/VGluT3-positive basket cells.

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