The role of calmodulin as a signal integrator for synaptic plasticity

Excitatory synapses in the brain show several forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), which are initiated by increases in intracellular Ca2+ that are generated through NMDA (N-methyl-D-aspartate) receptors or voltage-sensitive Ca2+ channels. LTP depends on the coordinated regulation of an ensemble of enzymes, including Ca2+/calmodulin-dependent protein kinase II, adenylyl cyclase 1 and 8, and calcineurin, all of which are stimulated by calmodulin, a Ca2+-binding protein. In this review, we discuss the hypothesis that calmodulin is a central integrator of synaptic plasticity and that its unique regulatory properties allow the integration of several forms of signal transduction that are required for LTP and LTD.