Ca2+ release from intracellular stores regulates muscle contraction and a vast array of cell functions, but its role in the central nervous system (CNS) has not been completely elucidated. A new method of blocking IP3 signaling by artificially expressing IP3 5-phosphatase has been used to clarify the functions of intracellular Ca2+ mobilization in CNS. Here I review two of such functions: the activity-dependent synaptic maintenance mechanism and the regulation of neuronal growth by spontaneous Ca2+ oscillations in astrocytes. These findings add new bases for better understanding CNS functions and suggest the presence of as yet unidentified neuronal and glial functions that are regulated by Ca2+ store-dependent Ca2+ signaling. (c) 2007 Elsevier Inc. All rights reserved.