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- Title
Activity Bidirectionally Regulates AMPA Receptor mRNA Abundance in Dendrites of Hippocampal Neurons.
- Authors
Grooms, Sonja Y.; Kyung-Min Noh; Regis, Roodland; Bassell, Gary J.; Bryan, Monique K.; Carroll, Reed C.; Zukin, R. Suzanne
- Abstract
Activity-dependent regulation of synaptic AMPA receptor (AMPAR) number is critical toNMDAreceptor (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. Asubstantial 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.
- Subjects
PHYSIOLOGICAL adaptation; IN situ hybridization; DENDRITES; NEURONS; MESSENGER RNA; PROTEIN synthesis; DENDRITIC cells
- Publication
Journal of Neuroscience, 2006, Vol 26, Issue 32, p8339
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0472-06.2006