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PMID: 16899729 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Grooms SY, Noh KM, Regis R, Bassell GJ, Bryan MK, Carroll RC, Zukin RS

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.

MeSH Terms
Animals Cells, Cultured Dendrites/metabolism Hippocampus/physiology Neuronal Plasticity/physiology Neurons/physiology RNA, Messenger/metabolism Rats Rats, Sprague-Dawley Receptors, AMPA/metabolism Synaptic Transmission/physiology Tissue Distribution
Chemicals
RNA, Messenger Receptors, AMPA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Grooms Sonja Y
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Noh Kyung-Min
Regis Roodland
Bassell Gary J
Bryan Monique K
Carroll Reed C
Zukin R Suzanne
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2006-08-09
Pages
8339-51
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6673809
Subset
IM
Grants
NINDS NIH HHS · NS049661 · United States
NINDS NIH HHS · NS20752 · United States
NINDS NIH HHS · NS51127 · United States
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