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

doi:10.1016/S0896-6273(03)00404-5

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

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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 and Eric R Kandel

Neuron (Cambridge, Mass.), Vol.39(2), pp.309-325

07/17/2003

DOI: 10.1016/S0896-6273(03)00404-5

PMID: 12873387

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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.

Details

Title: Subtitle: Rap1 couples cAMP signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning, and memory
Creators: Alexei Morozov
Isabel A Muzzio - Columbia University
Rusiko Bourtchouladze
Niels Van-Strien
Kyle Lapidus
DeQi Yin
Danny G Winder - Columbia University
J Paige Adams - Baylor College of Medicine
J David Sweatt - Baylor College of Medicine
Eric R Kandel - Columbia University
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.39(2), pp.309-325
DOI: 10.1016/S0896-6273(03)00404-5
PMID: 12873387
NLM abbreviation: Neuron
ISSN: 0896-6273
eISSN: 1097-4199
Language: English
Date published: 07/17/2003
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute
Record Identifier: 9984294926202771

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