Time domains of neuronal Ca2+ signaling and associative memory: steps through a calexcitin, ryanodine receptor, K+ channel cascade

Synaptic changes that underlie associative learning and memory begin with t emporally related activity of two or more independent synaptic inputs to co mmon postsynaptic targets. In turn, temporally related molecular events reg ulate cytosolic Ca2+ during progressively longer-lasting time domains,Assoc iative learning behaviors of living animals have been correlated with chang es of neuronal voltage-dependent K+ currents, protein kinase C-mediated pho sphorylation and synthesis of the Ca2+ and GTP-binding protein, calexcitin (CE), and increased expression of the Ca2+-releasing ryanodine receptor (ty pe II), These molecular events, some of which have been found to be dysfunc tional in Alzheimer's disease, provide means of altering dendritic excitabi lity and thus synaptic efficacy during induction, consolidation and storage of associative memory. Apparently, such stages of behavioral learning corr espond to sequential differences of Ca2+ signaling that could occur in spat ially segregated dendritic compartments distributed across brain structures , such as the hippocampus.