The role of Ca2+/calmodulin-stimulable adenylyl cyclases as molecular coincidence detectors in memory formation

Evidence from systems as diverse as mollusks, insects and mammals has revea led that adenylyl cyclase, cyclic adenosine 3',5'-monophosphate (cAMP) casc ade, cAMP-dependent protein kinases and their substrates are required for t he cellular events underlying the shortterm and long-term forms of memory. In Aplysia and Drosophila models, the coincident activation of independent paths converge to produce a synergistic activation of Ca2+/calmodulin-stimu lable adenylyl cyclase, thereby enhancing the cAMP level that appears as th e primary mediator of downstream events that strengthen enduring memory. In mammals, in which long-term memories require hippocampal function: our und erstanding of the role of adenylyl cyclases is still fragmentary. Of the di fferently regulated isoforms present in the hippocampus, the susceptibility of type 1 and type 8 to stimulation by the complex Ca2+/calmodulin and the ir expression in the hippocampus suggest a role for these two isoforms as a molecular coincidence device for hippocampus-related memory function. Here , we review the key features of Ca2+/calmodulin stimulable adenylyl cyclase s, as well as the involvement of cAMP-regulated signaling pathway in the pr ocesses of learning and memory.