An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling

Soren Impey, Monika Davare, Adam Lasiek, Dale Fortin, Hideaki Ando, Olga Varlamova, Karl Obrietan, Thomas R. Soderling, Richard H. Goodman, Gary A. Wayman

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

Activity-regulated gene expression is believed to play a key role in the development and refinement of neuronal circuitry. Nevertheless, the transcriptional networks that regulate synaptic plasticity remain largely uncharacterized. We show here that the CREB- and activity-regulated microRNA, miR132, is induced during periods of active synaptogenesis. Moreover, miR132 is necessary and sufficient for hippocampal spine formation. Expression of the miR132 target, p250GAP, is inversely correlated with miR132 levels and spinogenesis. Furthermore, knockdown of p250GAP increases spine formation while introduction of a p250GAP mutant unresponsive to miR132 attenuates this activity. Inhibition of miR132 decreases both mEPSC frequency and the number of GluR1-positive spines, while knockdown of p250GAP has the opposite effect. Additionally, we show that the miR132/p250GAP circuit regulates Rac1 activity and spine formation by modulating synapse-specific Kalirin7-Rac1 signaling. These data suggest that neuronal activity regulates spine formation, in part, by increasing miR132 transcription, which in turn activates a Rac1-Pak actin remodeling pathway.

Original languageEnglish (US)
Pages (from-to)146-156
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume43
Issue number1
DOIs
StatePublished - Jan 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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