The cAMP and Erk/MAP kinase (MAPK) signal transduction pathways are critical for hippocampus-dependent memory. However, the extent of coactivation and crosstalk between these pathways during fear conditioning has not been described. Here we report that PKA and MAPK are co-activated in a subset of hippocampal CA1 pyramidal neurons following contextual fear conditioning. Activation of MAPK was absolutely dependent on Ca²⁺-stimulated adenylyl cyclase activity. Furthermore, there was a strong correlation between stimulation of MAPK and MSK-1, a downstream CREB kinase. These data indicate that activation of adenylyl cyclase is critical for memory formation because PKA stimulation supports the nuclear translocation and activation of MAPK following training.