Signaling from cAMP/PKA to MAPK and synaptic plasticity

Authors: Waltereit, Robert¹; Weller, Michael²

Source: Molecular Neurobiology, Volume 27, Number 1, February 2003 , pp. 99-106(8)

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Abstract:

The facilitation of hippocampus-based, long-lasting synaptic plasticity, which is frequently investigated in model systems such as long-term potentiation (LTP) and in learning paradigms such as the Morris water maze, is associated with several cellular key events: Ca²⁺ influx through the n-methyl-d-aspartate (NMDA) receptor, generation of cyclic AMP (cAMP) and activation of protein kinase A (PKA), phosphorylation of mitogen-associated protein kinase (MAPK) and cAMP-response element-binding protein (CREB), and subsequent transcription of plasticity-associated genes.

Recently, a signal-transduction cascade from cAMP/PKA to MAPK was discovered, which seems to be neuron-specific and comprises the critical events of hippocampus-based long-term plasticity described here into one single cascade. A major alternative to cAMP/PKA-MAPK signaling are the cascades from Ca²⁺ to MAPK via Ras. However, Ras is inhibited by PKA. This article reviews the studies that argue for the existence of two competing pathways, and discusses their implication for the molecular mechanisms underlying synaptic plasticity.

Keywords: Long-term memory; hippocampus; synaptic plasticity; plasticity-associated genes; cAMP; PKA; Rap1; B-Raf; MAPK; CREB

Document Type: Research article

DOI: http://dx.doi.org/10.1385/MN:27:1:99

Affiliations: 1: Department of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany, Email: robert.waltereit@uni-tuebingen.de 2: Department of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany,

Publication date: 2003-02-01