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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Molecular and Morphological Configuration for 2-Arachidonoylglycerol-Mediated Retrograde Signaling at Mossy Cell-Granule Cell Synapses in the Dentate Gyrus
| Title: | Molecular and Morphological Configuration for 2-Arachidonoylglycerol-Mediated Retrograde Signaling at Mossy Cell-Granule Cell Synapses in the Dentate Gyrus |
| Authors: | Uchigashima, Motokazu Browse this author | | Yamazaki, Maya Browse this author | | Yamasaki, Miwako Browse this author | | Tanimura, Asami Browse this author | | Sakimura, Kenji Browse this author | | Kano, Masanobu Browse this author | | Watanabe, Masahiko Browse this author →KAKEN DB |
| Issue Date: | 25-May-2011 |
| Publisher: | Society for Neuroscience |
| Journal Title: | The Journal of Neuroscience |
| Volume: | 31 |
| Issue: | 21 |
| Start Page: | 7700 |
| End Page: | 7714 |
| Publisher DOI: | 10.1523/JNEUROSCI.5665-10.2011 |
| PMID: | 21613483 |
| Abstract: | 2-Arachidonoylglycerol (2-AG) is the endocannabinoid that mediates retrograde suppression of neurotransmission in the brain. In the present study, we investigated the 2-AG signaling system at mossy cell (MC)-granule cell (GC) synapses in the mouse dentate gyrus, an excitatory recurrent circuit where endocannabinoids are thought to suppress epileptogenesis. First, we showed by electrophysiology that 2-AG produced by diacylglycerol lipase α(DGLα) mediated both depolarization-induced suppression of excitation and its enhancement by group I metabotropic glutamate receptor activation at MC-GC synapses, as they were abolished in DGLα-knock-out mice. Immunohistochemistry revealed that DGLα was enriched in the neck portion of GC spines forming synapses with MC terminals, whereas cannabinoid CB1 receptors accumulated in the terminal portion of MC axons. On the other hand, the major 2-AG-degrading enzyme, monoacylglycerol lipase (MGL), was absent at MC-GC synapses but was expressed in astrocytes and some inhibitory terminals. Serial electron microscopy clarified that a given GC spine was innervated by a single MC terminal and also contacted nonsynaptically by other MC terminals making synapses with other GC spines in the neighborhood. MGL-expressing elements, however, poorly covered GC spines, amounting to 17% of the total surface of GC spines by astrocytes and 4% by inhibitory terminals. Our findings provide a basis for 2-AG-mediated retrograde suppression of MC-GC synaptic transmission and also suggest that 2-AG released from activated GC spines is readily accessible to nearby MC-GC synapses by escaping from enzymatic degradation. This molecular-anatomical configuration will contribute to adjust network activity in the dentate gyrus after enhanced excitation. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/47503 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 渡邉 雅彦
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