title: 'Silent' priming of translation-dependent LTP by ß-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors.
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.
authors.affiliation: Department of Physiology, University of Alberta School of Medicine, Edmonton, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Tenorio
authors.forename: Steven A
authors.initials: SA
authors.lastname: Connor
authors.forename: Diane
authors.initials: D
authors.lastname: Guévremont
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
authors.forename: Joanna
authors.initials: J
authors.lastname: Williams
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: O'Dell
authors.forename: Peter V
authors.initials: PV
authors.lastname: Nguyen
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001703:Biophysics; D002227:Carbazoles / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques / Q000379:methods; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011758:Pyrroles; D018091:Receptors, AMPA; D011943:Receptors, Adrenergic, beta; D012694:Serine; C057416:KT 5720; D011433:Propranolol; D007545:Isoproterenol; C104722:glutamate receptor ionotropic, AMPA 2