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Microtubule-associated protein 2 mediates induction of long-term potentiation in hippocampal neurons

Title
Microtubule-associated protein 2 mediates induction of long-term potentiation in hippocampal neurons
Authors
Kim, YoonjuJang, You-NaKim, Ji-YoungKim, NariNoh, SeulgiKim, HyeyeonQueenan, Bridget N.Bellmore, RyanMun, Ji YoungPark, HyungjuRah, Jong CheolPak, Daniel T. S.Lee, Kea Joo
DGIST Authors
Kim, Yoonju; Jang, You-Na; Kim, Ji-Young; Kim, Nari; Noh, Seulgi; Kim, Hyeyeon; Queenan, Bridget N.; Bellmore, Ryan; Mun, Ji Young; Park, Hyungju; Rah, Jong Cheol; Pak, Daniel T. S.; Lee, Kea Joo
Issue Date
2020-05
Citation
FASEB Journal, 34(5), 6965-6983
Type
Article
Article Type
Article
Author Keywords
dendritic spineelectron microscopyMAP2synaptic plasticity
Keywords
DENDRITIC SPINE MORPHOLOGYAMPA RECEPTORSNMDA RECEPTORSSTRUCTURAL PLASTICITYBIDIRECTIONAL CONTROLMAP2 PHOSPHORYLATIONSIGNALING PATHWAYACTINACTIVATIONKINASE
ISSN
0892-6638
Abstract
Microtubule-associated protein (MAP) 2 has been perceived as a static cytoskeletal protein enriched in neuronal dendritic shafts. Emerging evidence indicates dynamic functions for various MAPs in activity-dependent synaptic plasticity. However, it is unclear how MAP2 is associated with synaptic plasticity mechanisms. Here, we demonstrate that specific silencing of high-molecular-weight MAP2 in vivo abolished induction of long-term potentiation (LTP) in the Schaffer collateral pathway of CA1 pyramidal neurons and in vitro blocked LTP-induced surface delivery of AMPA receptors and spine enlargement. In mature hippocampal neurons, we observed rapid translocation of a subpopulation of MAP2, present in dendritic shafts, to spines following LTP stimulation. Time-lapse confocal imaging showed that spine translocation of MAP2 was coupled with LTP-induced spine enlargement. Consistently, immunogold electron microscopy revealed that LTP stimulation of the Schaffer collateral pathway promoted MAP2 labeling in spine heads of CA1 neurons. This translocation depended on NMDA receptor activation and Ras-MAPK signaling. Furthermore, LTP stimulation led to an increase in surface-expressed AMPA receptors specifically in the neurons with MAP2 spine translocation. Altogether, this study indicates a novel role for MAP2 in LTP mechanisms and suggests that MAP2 participates in activity-dependent synaptic plasticity in mature hippocampal networks. © 2020 The Authors.
URI
http://hdl.handle.net/20.500.11750/11661
DOI
10.1096/fj.201902122RR
Publisher
Federation of American Societies for Experimental Biology
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