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Fluctuations of cytosolic Ca 2+  concentration in astrocytes are regarded as a critical non-neuronal signal to regulate neuronal functions. Although such fluctuations can be evoked by neuronal activity, rhythmic astrocytic Ca 2+  oscillations may also spontaneously arise. Experimental studies hint that these spontaneous astrocytic Ca 2+  oscillations may lie behind different kinds of emerging neuronal synchronized activities, like epileptogenic bursts or slow-wave rhythms. Despite the potential importance of spontaneous Ca 2+  oscillations in astrocytes, the mechanism by which they develop is poorly understood. Using simple 3D synapse models and kinetic data of astrocytic Glu transporters (EAATs) and the Na + /Ca 2+  exchanger (NCX), we have previously shown that NCX activity alone can generate markedly stable, spontaneous Ca 2+  oscillation in the astrocytic leaflet microdomain. Here, we extend that model by incorporating experimentally determined real 3D geometries of 208 excitatory synapses reconstructed from publicly available ultra-resolution electron microscopy datasets. Our simulations predict that the surface/volume ratio (SVR) of peri-synaptic astrocytic processes prominently dictates whether NCX-mediated spontaneous Ca 2+  oscillations emerge. We also show that increased levels of intracellular astrocytic Na +  concentration facilitate the appearance of Ca 2+  fluctuations. These results further support the principal role of the dynamical reshaping of astrocyte processes in the generation of intrinsic Ca 2+  oscillations and their spreading over larger astrocytic compartments.

Spontaneous Ca2+ Fluctuations Arise in Thin Astrocytic Processes With Real 3D Geometry