title: Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus.
abstract: Gene expression regulated by the cAMP response element (CRE) has been implicated in synaptic plasticity and long-term memory. It has been proposed that CRE-mediated gene expression is stimulated by signals that induce long-term potentiation (LTP). To test this hypothesis, we made mice transgenic for a CRE-regulated reporter construct. We focused on long-lasting long-term potentiation (L-LTP), because it depends on cAMP-dependent protein kinase activity (PKA) and de novo gene expression. CRE-mediated gene expression was markedly increased after L-LTP, but not after decremental UP (D-LTP). Furthermore, inhibitors of PKA blocked L-LTP and associated increases in CRE-mediated gene expression. These data demonstrate that the signaling required for the generation of L-LTP but not D-LTP is sufficient to stimulate CRE-mediated transcription in the hippocampus.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, 98195, USA.
authors.forename: S
authors.initials: S
authors.lastname: Impey
authors.forename: M
authors.initials: M
authors.lastname: Mark
authors.forename: E C
authors.initials: EC
authors.lastname: Villacres
authors.forename: S
authors.initials: S
authors.lastname: Poser
authors.forename: C
authors.initials: C
authors.lastname: Chavkin
authors.forename: D R
authors.initials: DR
authors.lastname: Storm
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000502:physiology; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction
chemical_list: D015220:Calcium Channels; D017362:Cyclic AMP Response Element-Binding Protein; D011953:Receptors, Cyclic AMP; D016194:Receptors, N-Methyl-D-Aspartate; D000242:Cyclic AMP; D011494:Protein Kinases