Neuron
Volume 39, Issue 2, 17 July 2003, Pages 309-325
Journal home page for Neuron

Article
Rap1 Couples cAMP Signaling to a Distinct Pool of p42/44MAPK Regulating Excitability, Synaptic Plasticity, Learning, and Memory

https://doi.org/10.1016/S0896-6273(03)00404-5Get rights and content
Under an Elsevier user license
open archive

Abstract

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.

Cited by (0)

4

These authors contributed equally to this work.

5

Present address: National Institutes of Health, National Institutes of Mental Health, 49 Convent Drive, Bethesda, Maryland 20892.

6

Present address: Helicon Therapeutics, Inc., 1 Bioscience Park Drive, Farmingdale, New York 11735.

7

Present address: Department of Molecular Physiology and Biophysics, Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.