Morozov A, Muzzio IA, Bourtchouladze R, Van-Strien N, Lapidus K, Yin D, Winder DG, Adams JP, Sweatt JD, Kandel ER
Neuron. 2003 39 (2)
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.
MeSH Terms (41)Animals Antirheumatic Agents Bacterial Proteins Behavior, Animal Blotting, Western Colforsin Conditioning (Psychology) Cues Cyclic AMP Electric Stimulation Electrophysiology Excitatory Postsynaptic Potentials Gene Expression Regulation, Enzymologic Hippocampus Immunoenzyme Techniques In Situ Hybridization Interleukin 1 Receptor Antagonist Protein Long-Term Potentiation Memory Metalloproteins Mice Mice, Transgenic Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Mutation Neuronal Plasticity Prosencephalon Proto-Oncogene Proteins B-raf Proto-Oncogene Proteins c-raf rap1 GTP-Binding Proteins Reaction Time RNA, Messenger Sialoglycoproteins Signal Transduction Subcellular Fractions Synapses Synaptic Transmission Tetanus Theta Rhythm Valine