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miRNAs are required for long-lasting spine remodeling associated with LTD

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NIMH

NEURO-12

Authors

  • Z Hu
  • D Yu
  • Q Gu
  • Y Yang
  • J Zhu
  • Z Li

Abstract

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 remodeling of spines. The mechanisms underlying long-lasting spine remodeling 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 found surprisingly 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 novel miRNA mediated-mechanism for and a new role of AMPA receptor exocytosis in long-lasting spine plasticity, and identify a comprehensive list of candidate “plasticity miRNAs” for LTD.

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