Activation of Mitogen-Activated Protein Kinases and Cyclic Amp Response Element-Binding Protein in Synaptic Plasticity.

摘要

Current evidence supports a critical role for cAMP in synaptic plasticity. Forskolin increases adenylyl cyclase activity to generate cAMP which induces a long-lasting potentiation of excitatory postsynaptic potentials in the hippocaznpal dentate gyrus to 137 plus or minus 5% of control, which persists for at least 60 min after forskolin removal. Blockade of NMDA (N- metbyl-D-aspartate) receptors with 20 micrometers 2-amino-5-phosphonovalerate (APV) or L-type calcium channels with 10 micrometers nifedipine, reduced this potentiation. TMB-8 (8- (diethylamino) octyl-3, 4, 5-trimethoxybenzoate, 50 micrometers), which interferes with calcium release from an inositol-3, 4, 5- trisphosphate (IP3) receptor-sensitive internal pool, also reduced forskolin potentiation. These data indicate that calcium from both extracellular and intracellular pools mediate the long-lasting,cAMP-mediated potentiation induced with forskolin in the dentate gyrus.