REPEATED PULSES OF SEROTONIN REQUIRED FOR LONG-TERM FACILITATION ACTIVATE MITOGEN-ACTIVATED PROTEIN-KINASE IN SENSORY NEURONS OF APLYSIA

Long-term facilitation of the connections between the sensory and moto r neurons of the gill-withdrawal reflex in Aplysia requires five repea ted pulses of serotonin (5-HT). The repeated pulses of 5-HT initiate a cascade of gene activation that leads ultimately to the growth of new synaptic connections. Several genes in this process have been identif ied, including the transcriptional regulators apCREB-1, apCREB-2, apC/ EBP, and the cell adhesion molecule apCAM, which is thought to be invo lved in the formation of new synaptic connections. Here we report that the transcriptional regulators apCREB-2 and apC/EBP, as well as a pep tide derived from the cytoplasmic domain of apCAM, are phosphorylated in vitro by Aplysia mitogen-activated protein kinase (apMAPK). We have cloned the cDNA encoding apMAPK and show that apMAPK activity is incr eased in sensory neurons treated with repeated pulses of 5-HT and by t he cAMP pathway. These results suggest that apMAPK may participate wit h cAMP-dependent protein kinase during long-term facilitation in senso ry cells by modifying some of the key elements involved in the consoli dation of short-to long-lasting changes in synaptic strength.