Rap1 couples cAMP signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning, and memory.

Alexei Morozov, Isabel A Muzzio, Rusiko Bourtchouladze, Niels Van-Strien, Kyle Lapidus, DeQi Yin, Danny G Winder, J Paige Adams, J David Sweatt, Eric R Kandel

Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, 1051 Riverside Drive, New York, NY 10032, USA.

Neuron 2003 Jul 17

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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.

Citation

Alexei Morozov, Isabel A Muzzio, Rusiko Bourtchouladze, Niels Van-Strien, Kyle Lapidus, DeQi Yin, Danny G Winder, J Paige Adams, J David Sweatt, Eric R Kandel. Rap1 couples cAMP signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning, and memory. Neuron. 2003 Jul 17;39(2):309-25