Calcium (Ca²⁺) plays fundamental and diversified roles in neuronal plasticity. As second messenger of many signaling pathways, Ca²⁺ 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 Ca²⁺ signaling is achieved by modifying cytosolic Ca²⁺ concentrations via regulated opening of plasma membrane and subcellular Ca²⁺ sensitive channels. The spatiotemporal patterns of intracellular Ca²⁺ signals, and the ultimate cellular biological outcome, are also dependent upon termination mechanism, such as Ca²⁺ buffering, extracellular extrusion, and intra-organelle sequestration. Because of the central role played by Ca²⁺ in neuronal physiology, it is not surprising that even modest impairments of Ca²⁺ 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 Ca²⁺ homeostasis and signaling. In this review we provide an overview of the main types of neuronal Ca²⁺ channels and their role in neuronal plasticity. We will also discuss the participation of Ca²⁺ signaling in neuronal aging and degeneration.

The hippocampus is crucial for memory formation. New neurons are added throughout life to the hippocampal dentate gyrus (DG), a brain area considered important for differential storage of similar experiences and contexts. To better understand the functional contribution of adult neurogenesis to pattern separation processes, we recently used a novel synapse specific trans-neuronal tracing approach to identify the (sub) cortical inputs to new dentate granule cells. It was observed that newly born neurons receive sequential innervation from structures important for memory function. Initially, septal-hippocampal cells provide input to new neurons, followed after about one month by perirhinal and lateral entorhinal cortex. These cortical areas are deemed relevant to encoding of novel environmental information and may enable pattern separation. Here, we review the developmental time-course and proposed functional relevance of new neurons, within the context of their unique neural circuitry.