The Ca(2+)/calmodulin-stimulated adenylyl cyclases, AC1 and AC8, play a critical role in several forms of neuroplasticity, including long-lasting long-term potentiation (L-LTP) and long-term memory (LTM). By coupling neuronal activity and Ca(2+) increases to the production of cAMP, AC1 and AC8 activate cAMP-dependent signal transduction and transcriptional pathways critical for L-LTP and LTM.