Activity bidirectionally regulates AMPA receptor mRNA abundance in dendrites of hippocampal neurons

Sonja Y. Grooms, Kyung Min Noh, Roodland Regis, Gary J. Bassell, Monique K. Bryan, Reed C. Carroll, R. Suzanne Zukin

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Activity-dependent regulation of synaptic AMPA receptor (AMPAR) number is critical to NMDA receptor (NMDAR)-dependent synaptic plasticity. Using quantitative high-resolution in situ hybridization, we show that mRNAs encoding the AMPA-type glutamate receptor subunits (GluRs) 1 and 2 are localized to dendrites of hippocampal neurons and are regulated by paradigms that alter synaptic efficacy. A substantial fraction of synaptic sites contain AMPAR mRNA, consistent with strategic positioning and availability for "on-site" protein synthesis. NMDAR activation depletes dendritic levels of AMPAR mRNAs. The decrease in mRNA occurs via rise in intracellular Ca2+, activation of extracellular signal-regulated kinase/mitogen-activated protein kinase signaling, and transcriptional arrest at the level of the nucleus. The decrease in mRNA is accompanied by a long-lasting reduction in synaptic AMPAR number, consistent with reduced synaptic efficacy. In contrast, group I metabotropic GluR signaling promotes microtubule-based trafficking of existing AMPAR mRNAs from the soma to dendrites. Bidirectional regulation of dendritic mRNA abundance represents a potentially powerful means to effect long-lasting changes in synaptic strength.

Original languageEnglish (US)
Pages (from-to)8339-8351
Number of pages13
JournalJournal of Neuroscience
Volume26
Issue number32
DOIs
StatePublished - Aug 9 2006

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Keywords

  • AMPA receptors
  • Dendrites
  • Messenger RNA
  • Synaptic plasticity
  • Transcription
  • mRNA trafficking

ASJC Scopus subject areas

  • Neuroscience(all)

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