Spatiotemporal pattern of calcium activity in astrocytic network.

Ca influx through an astrocyte plasma membrane is mediated by ionotropic receptors and Ca channels according the electrochemical gradient. These conductances allow astrocytes to sense the levels of neuronal activity and environmental changes. Na/Ca exchanger (NCX) removes elevated Ca from the cell but can reverse and bring Ca in. Ca entry through the plasma membrane produces local Ca elevations that can be further amplified by Ca induced activation of inositol-3-phosphate (IP) receptors and subsequent Ca release from intracellular Ca stores. These Ca 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 Ca 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 Ca events. Therefore, morphological remodeling of the processes is an important regulator of astrocytic Ca activity. Ca events can propagate beyond single astrocytes and form complex spatiotemporal patterns of Ca activity in the astrocytic network. Ca events spread intercellularly through gap-junctions and via extracellular ATP diffusion. Spatially and temporarily organized Ca 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 Ca 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.