Rap1 Couples cAMP Signaling to a Distinct Pool of p42/44MAPK Regulating Excitability, Synaptic Plasticity, Learning, and Memory
Copyright policy )Rap1 Couples cAMP Signaling to a Distinct Pool of p42/44MAPK Regulating Excitability, Synaptic Plasticity, Learning, and Memory
Learning-induced synaptic plasticity commonly involves the interaction between cAMP and p42/44MAPK. To investigate the role of Rap1 as a potential signaling molecule coupling cAMP and p42/44MAPK, we expressed an interfering Rap1 mutant (iRap1) in the mouse forebrain. This expression selectively decreased basal phosphorylation of a membrane-associated pool of p42/44MAPK, impaired cAMP-dependent LTP in the hippocampal Schaffer collateral pathway induced by either forskolin or theta frequency stimulation, decreased complex spike firing, and reduced the p42/44MAPK-mediated phosphorylation of the A-type potassium channel Kv4.2. These changes correlated with impaired spatial memory and context discrimination. These results indicate that Rap1 couples cAMP signaling to a selective membrane-associated pool of p42/44MAPK to control excitability of pyramidal cells, the early and late phases of LTP, and the storage of spatial memory.
- Vanderbilt University United States
- Baylor College of Medicine United States
- King’s University United States
- Howard Hughes Medical Institute
- Howard Hughes Medical Institute
Behavior, Animal, Neuroscience(all), Blotting, Western, Colforsin, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Hippocampus, Electric Stimulation, Gene Expression Regulation, Enzymologic, Electrophysiology, Immunoenzyme Techniques, Interleukin 1 Receptor Antagonist Protein, Bacterial Proteins, Memory, Antirheumatic Agents, Conditioning, Psychological, Metalloproteins, Cyclic AMP, Animals, Cues, In Situ Hybridization
Behavior, Animal, Neuroscience(all), Blotting, Western, Colforsin, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Hippocampus, Electric Stimulation, Gene Expression Regulation, Enzymologic, Electrophysiology, Immunoenzyme Techniques, Interleukin 1 Receptor Antagonist Protein, Bacterial Proteins, Memory, Antirheumatic Agents, Conditioning, Psychological, Metalloproteins, Cyclic AMP, Animals, Cues, In Situ Hybridization
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