Spatiotemporal pattern of calcium activity in astrocytic network.

Ca2+ influx through an astrocyte plasma membrane is mediated by ionotropic receptors and Ca2+ channels according the electrochemical gradient. These conductances allow astrocytes to sense the levels of neuronal activity and environmental changes. Na+/Ca2+ exchanger (NCX) removes elevated Ca2+ from the cell but can reverse and bring Ca2+ in. Ca2+ entry through the plasma membrane produces local Ca2+ elevations that can be further amplified by Ca2+ induced activation of inositol-3-phosphate (IP3) receptors and subsequent Ca2+ release from intracellular Ca2+ stores. These Ca2+ stores are located in astrocytic processes called branchlets, while perisynaptic astrocytic processes are formed by organelle-free leaflets. Such morphological structure suggests separate synaptic and extrasynaptic mechanisms of Ca2+ signaling in astrocytes. Astrocytic leaflets sense synaptic activity, astrocytic branchlets integrate signals arriving from the leaflets and from extrasynaptic inputs. The surface-to-volume ratio (SVR) of the branchlets sets the threshold for generation of spreading Ca2+ events. Therefore, morphological remodeling of the processes is an important regulator of astrocytic Ca2+ activity. Ca2+ events can propagate beyond single astrocytes and form complex spatiotemporal patterns of Ca2+ activity in the astrocytic network. Ca2+ events spread intercellularly through gap-junctions and via extracellular ATP diffusion. Spatially and temporarily organized Ca2+ events in astrocytic network influence variable numbers of synapses and neuronal compartments, gate excitation flow and synaptic plasticity in the neuronal network through the release of gliotransmitters. Thus, multiple patterns of Ca2+ activity in the astrocytic network (guiding templates) determine multiple states of the neuronal network. This phenomenon may be linked to learning, memory and information processing in the brain.