Synaptic transmission is a key signaling event, whereby an action potential-induced release of chemical neurotransmitters again generates a positive or negative electrical activity via opening of postsynaptic channels. Thereafter, information spreads through space, from the postsynaptic membranes to the dendrites, to the soma, to the nucleus, to the presynaptic terminals and, in some cases, back to the originally stimulated synapses. Furthermore, information is also often converted in time, either by shifting the phase of electrical activity during the integration of EPSPs and IPSPs into the generation of an action potential, or by triggering a long-lasting cascade of enzymatic or protein-protein interaction-mediated events in the cytoplasm and in the nucleus. Recent studies of the signaling from the synapse to the nucleus now allow us to consider how various patterns of synaptic activity could couple with activation of specific nuclear transcription factors and thus regulate neuronal gene expression. The critical importance of Ca(2+)-dependent signaling processes in such regulatory events will be discussed below.