Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus.
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.
Impey
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Department of Pharmacology, School of Medicine, University of Washington, Seattle, 98195, USA.
Mark
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Villacres
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Poser
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Chavkin
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Storm
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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
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