title: Beta-adrenergic receptor activation facilitates induction of a protein synthesis-dependent late phase of long-term potentiation.
abstract: Long-term potentiation (LTP) is activity-dependent enhancement of synaptic strength that can critically regulate long-term memory storage. Like memory, LTP exhibits at least two mechanistically distinct temporal phases. Early LTP (E-LTP) does not require protein synthesis, whereas the late phase of LTP (L-LTP), like long-term memory, requires protein synthesis. Hippocampal beta-adrenergic receptors can regulate expression of both E-LTP and long-term memory. Although beta-adrenergic receptor activation enhances the ability of subthreshold stimuli to induce E-LTP, it is unclear whether such activation can facilitate induction of L-LTP. Here, we use electrophysiological recording methods on mouse hippocampal slices to show that when synaptic stimulation that is subthreshold for inducing L-LTP is paired with beta-adrenergic receptor activation, the resulting LTP persists for over 6 h in area CA1. Like L-LTP induced by multiple trains of high-frequency electrical stimulation, this LTP requires protein synthesis. Unlike tetanus-induced L-LTP, however, L-LTP induced by beta-adrenergic receptor activation during subthreshold stimulation appears to involve dendritic protein synthesis but not somatic transcription. Maintenance of this LTP also requires activation of extracellular signal-regulated kinases (ERKs). Thus, beta-adrenergic receptor activation elicits a type of L-LTP that requires translation and ERK activation but not transcription. This form of L-LTP may be a cellular mechanism for facilitation of behavioral long-term memory during periods of heightened emotional arousal that engage the noradrenergic modulatory system.
authors.affiliation: Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta, Canada T6G 2H7.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Gelinas
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; D000841:Anisomycin / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000031:analogs & derivatives / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011433:Propranolol / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011500:Protein Synthesis Inhibitors; D011943:Receptors, Adrenergic, beta; D003609:Dactinomycin; C011003:isolevin; D000841:Anisomycin; D011433:Propranolol; D007545:Isoproterenol; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one