‘Silent’ priming of translation-dependent LTP by β-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors
- Gustavo Tenorio1,6,
- Steven A. Connor2,6,
- Diane Guévremont3,
- Wickliffe C. Abraham4,
- Joanna Williams3,
- Thomas J. O'Dell5 and
- Peter V. Nguyen1,2,7
- 1Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta, T6G 2H7, Canada
- 2Centre for Neuroscience, University of Alberta School of Medicine, Edmonton, Alberta, T6G 2H7, Canada
- 3Department of Anatomy and Structural Biology, Brain Health and Repair Research Centre, University of Otago, Dunedin 9054, New Zealand
- 4Department of Psychology, Brain Health and Repair Research Centre, University of Otago, Dunedin 9054, New Zealand
- 5Department of Physiology, David Geffen School of Medicine, Center for the Health Sciences, University of California, Los Angeles, California 90095-1751, USA
-
↵6 These authors contributed equally to this work.
Abstract
The capacity for long-term changes in synaptic efficacy can be altered by prior synaptic activity, a process known as “metaplasticity.” Activation of receptors for modulatory neurotransmitters can trigger downstream signaling cascades that persist beyond initial receptor activation and may thus have metaplastic effects. Because activation of β-adrenergic receptors (β-ARs) strongly enhances the induction of long-term potentiation (LTP) in the hippocampal CA1 region, we examined whether activation of these receptors also had metaplastic effects on LTP induction. Our results show that activation of β-ARs induces a protein synthesis-dependent form of metaplasticity that primes the future induction of late-phase LTP by a subthreshold stimulus. β-AR activation also induced a long-lasting increase in phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 subunits at a protein kinase A (PKA) site (S845) and transiently activated extracellular signal-regulated kinase (ERK). Consistent with this, inhibitors of PKA and ERK blocked the metaplastic effects of β-AR activation. β-AR activation also induced a prolonged, translation-dependent increase in cell surface levels of GluA1 subunit-containing AMPA receptors. Our results indicate that β-ARs can modulate hippocampal synaptic plasticity by priming synapses for the future induction of late-phase LTP through up-regulation of translational processes, one consequence of which is the trafficking of AMPARs to the cell surface.
Footnotes
-
↵7 Corresponding author.
E-mail peter.nguyen{at}ualberta.ca; fax (780) 492-8915.
- Received August 5, 2010.
- Accepted September 28, 2010.
- © 2010 Cold Spring Harbor Laboratory Press