TY - JOUR
T1 - MiR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression
AU - Hu, Zhonghua
AU - Yu, Danni
AU - Gu, Qin Hua
AU - Yang, Yanqin
AU - Tu, Kang
AU - Zhu, Jun
AU - Li, Zheng
N1 - Funding Information:
We thank Dr Song Jiao for help with preparation of acute hippocampal slices, Dr Heinz Arnheiter for intense discussions of this study and critical reading of the manuscript and Dr Elizabeth J. Sherman for a close reading and editing of the manuscript. This work was supported by the NIMH and the NHLBI Intramural Programs.
PY - 2014/2/18
Y1 - 2014/2/18
N2 - Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.
AB - Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.
UR - http://www.scopus.com/inward/record.url?scp=84894378475&partnerID=8YFLogxK
U2 - 10.1038/ncomms4263
DO - 10.1038/ncomms4263
M3 - Article
C2 - 24535612
AN - SCOPUS:84894378475
SN - 2041-1723
VL - 5
JO - Nature Communications
JF - Nature Communications
M1 - 3263
ER -