Activity bidirectionally regulates AMPA receptor mRNA abundance in dendrites of hippocampal neurons.
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.
Grooms
Sonja Y
SY
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Noh
Kyung-Min
KM
Regis
Roodland
R
Bassell
Gary J
GJ
Bryan
Monique K
MK
Carroll
Reed C
RC
Zukin
R Suzanne
RS
D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D014018:Tissue Distribution
D012333:RNA, Messenger; D018091:Receptors, AMPA