Physiology and pathology of calcium signaling in the brain

Calcium (Ca(2+)) plays fundamental and diversified roles in neuronal plasticity. As second messenger of many signaling pathways, Ca(2+) as been shown to regulate neuronal gene expression, energy production, membrane excitability, synaptogenesis, synaptic transmission, and other processes underlying learning and memory and cell survival. The flexibility of Ca(2+) signaling is achieved by modifying cytosolic Ca(2+) concentrations via regulated opening of plasma membrane and subcellular Ca(2+) sensitive channels. The spatiotemporal patterns of intracellular Ca(2+) signals, and the ultimate cellular biological outcome, are also dependent upon termination mechanism, such as Ca(2+) buffering, extracellular extrusion, and intra-organelle sequestration. Because of the central role played by Ca(2+) in neuronal physiology, it is not surprising that even modest impairments of Ca(2+) homeostasis result in profound functional alterations. Despite their heterogeneous etiology neurodegenerative disorders, as well as the healthy aging process, are all characterized by disruption of Ca(2+) homeostasis and signaling. In this review we provide an overview of the main types of neuronal Ca(2+) channels and their role in neuronal plasticity. We will also discuss the participation of Ca(2+) signaling in neuronal aging and degeneration.