PT  - JOURNAL ARTICLE
AU  - Erik D. Roberson
AU  - Joey D. English
AU  - J. Paige Adams
AU  - Joel C. Selcher
AU  - Christine Kondratick
AU  - J. David Sweatt
TI  - The Mitogen-Activated Protein Kinase Cascade Couples PKA and PKC to cAMP Response Element Binding Protein Phosphorylation in Area CA1 of Hippocampus
AID  - 10.1523/JNEUROSCI.19-11-04337.1999
DP  - 1999 Jun 01
TA  - The Journal of Neuroscience
PG  - 4337--4348
VI  - 19
IP  - 11
4099  - http://www.jneurosci.org/content/19/11/4337.short
4100  - http://www.jneurosci.org/content/19/11/4337.full
SO  - J. Neurosci.1999 Jun 01; 19
AB  - Activation of the mitogen-activated protein kinase (MAPK) cascade recently was discovered to play an important role in synaptic plasticity in area CA1 of rat hippocampus. However, the upstream mechanisms regulating MAPK activity and the downstream effectors of MAPK in the hippocampus are uncharacterized. In the present studies we observed that hippocampal MAPK activation is regulated by both the PKA and PKC systems; moreover, we found that a wide variety of neuromodulatory neurotransmitter receptors (metabotropic glutamate receptors, muscarinic acetylcholine receptors, dopamine receptors, and β-adrenergic receptors) couple to MAPK activation via these two cascades. In additional studies we observed that PKC is a powerful regulator of CREB phosphorylation in area CA1. MAPK plays a critical role in transcriptional regulation by PKC, because MAPK activation is a necessary component for increased CREB phosphorylation in response to the activation of this kinase. Surprisingly, we also observed that MAPK activation is necessary for PKA coupling to CREB phosphorylation in area CA1. Overall, these studies indicate an unexpected richness of diversity in the regulation of MAPK in the hippocampus and suggest the possibility of a broad role for the MAPK cascade in regulating gene expression in long-term forms of hippocampal synaptic plasticity.