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TARP γ-2 and γ-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area
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| Title: | TARP γ-2 and γ-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area |
| Authors: | Yamasaki, Miwako Browse this author →KAKEN DB | | Fukaya, Masahiro Browse this author →KAKEN DB | | Yamazaki, Maya Browse this author →KAKEN DB | | Azechi, Hirotsugu Browse this author | | Natsume, Rie Browse this author →KAKEN DB | | Abe, Manabu Browse this author →KAKEN DB | | Sakimura, Kenji Browse this author →KAKEN DB | | Watanabe, Masahiko Browse this author →KAKEN DB |
| Keywords: | AMPA receptor | | hippocampus | | interneuron | | perforated synapse | | pyramidal cell | | transmembrane AMPAR regulatory proteins |
| Issue Date: | 13-Apr-2016 |
| Publisher: | Society for Neuroscience |
| Journal Title: | Journal of neuroscience |
| Volume: | 36 |
| Issue: | 15 |
| Start Page: | 4296 |
| End Page: | 4312 |
| Publisher DOI: | 10.1523/JNEUROSCI.4178-15.2016 |
| PMID: | 27076426 |
| Abstract: | The number of AMPA-type glutamate receptors (AMPARs) at synapses is the major determinant of synaptic strength and varies from synapse to synapse. To clarify the underlying molecular mechanisms, the density of AMPARs, PSD-95, and transmembrane AMPAR regulatory proteins (TARPs) were compared at Schaffer collateral/commissural (SCC) synapses in the adult mouse hippocampal CA1 by quantitative immunogold electron microscopy using serial sections. We examined four types of SCC synapses: perforated and nonperforated synapses on pyramidal cells and axodendritic synapses on parvalbumin-positive (PV synapse) and pravalbumin-negative interneurons (non-PV synapse). SCC synapses were categorized into those expressing high-density (perforated and PV synapses) or low-density (nonperforated and non-PV synapses) AMPARs. Although the density of PSD-95 labeling was fairly constant, the density and composition of TARP isoforms was highly variable depending on the synapse type. Of the three TARPs expressed in hippocampal neurons, the disparity in TARP γ-2 labeling was closely related to that of AMPAR labeling. Importantly, AMPAR density was significantly reduced at perforated and PV synapses in TARP γ-2-knock-out (KO) mice, resulting in a virtual loss of AMPAR disparity among SCC synapses. In comparison, TARP γ-8 was the only TARP expressed at nonperforated synapses, where AMPAR labeling further decreased to a background level in TARP γ-8-KO mice. These results show that synaptic inclusion of TARP γ-2 potently increases AMPAR expression and transforms low-density synapses into high-density ones, whereas TARP γ-8 is essential for low-density or basal expression of AMPARs at nonperforated synapses. Therefore, these TARPs are critically involved in AMPAR density control at SCC synapses. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/63068 |
| 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: 山崎 美和子
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