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

• Published in: The FASEB journal Vol. 34; no. 5; pp. 6965 - 6983
• Main 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
• Format: Journal Article
• Language: English
• Published: United States 01.05.2020
• Subjects: Animals; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - metabolism; Cells, Cultured; dendritic spine; Dendritic Spines - metabolism; Dendritic Spines - ultrastructure; electron microscopy; In Vitro Techniques; Long-Term Potentiation - physiology; Male; MAP Kinase Signaling System; MAP2; Mice, Inbred C57BL; Microscopy, Immunoelectron; Microtubule-Associated Proteins - antagonists & inhibitors; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Neuronal Plasticity - physiology; Protein Transport; Pyramidal Cells - metabolism; Pyramidal Cells - ultrastructure; Rats; Receptors, AMPA - metabolism; RNA Interference; RNA, Small Interfering - genetics; synaptic plasticity; electron microscopy; dendritic spine; synaptic plasticity; MAP2
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201902122RR

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.