Molecular Neurobiology

, Volume 27, Issue 1, pp 99–106 | Cite as

Signaling from cAMP/PKA to MAPK and synaptic plasticity



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.

Index Entries

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


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© Humana Press Inc 2003

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of TübingenTübingenGermany

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