title: Adenylyl cyclase-dependent form of chemical long-term potentiation triggers translational regulation at the elongation step.
abstract: The persistent maintenance of long-term potentiation requires both messenger RNA and protein synthesis. While there is mounting evidence for an active role of protein synthesis in hippocampal long-term potentiation, the nature of mechanisms underlying its regulation has not yet been established. We used a previously described chemical long-term potentiation protocol [J Neurosci 19 (1999) 2500] to address the hypothesis that signaling mechanisms, involved in long-lasting long-term potentiation, directly regulate protein synthesis. Chemical long-term potentiation is an N-methyl-D-aspartate receptor-dependent form of plasticity, which relies on both synaptic activity, in the form of spontaneous bursting induced by high concentrations of K(+) and Ca(2+), and cyclic AMP/adenylyl cyclase signaling. We found that chemical long-term potentiation in CA1 of the mouse hippocampus lasts for at least 3 hours and requires both messenger RNA and protein synthesis. However, surprisingly de novo total protein synthesis was paradoxically decreased at 1 hour after long-term potentiation induction. Consistent with the decrease in total protein synthesis in potentiated CA1, phosphorylation of eukaryotic elongation factor 2 was increased and is likely responsible for inhibition of translation at the elongation step. Increased phosphorylation of eukaryotic elongation factor 2 was dependent on coincident cyclic AMP/adenylyl cyclase activation and synaptic activity and required N-methyl-D-aspartate receptor activation. Despite the inhibition in total protein synthesis, the level of the immediate early gene protein Arc (activity regulated cytoskeleton-associated protein) increased at 1 hour after chemical long-term potentiation induction. Taken together, the results suggest that regulation at the elongation step of protein synthesis contributes to persistent forms of long-term potentiation.
authors.affiliation: Interdepartmental Graduate Program for Neuroscience, University of California Los Angeles School of Medicine, 90095, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Chotiner
authors.forename: H
authors.initials: H
authors.lastname: Khorasani
authors.forename: A C
authors.initials: AC
authors.lastname: Nairn
authors.forename: T J
authors.initials: TJ
authors.lastname: O'Dell
authors.forename: J B
authors.initials: JB
authors.lastname: Watson
mesh_terms: D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D006624:Hippocampus / Q000201:enzymology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D000262:Adenylyl Cyclases