Spontaneous Ca Fluctuations Arise in Thin Astrocytic Processes With Real 3D Geometry.

Fluctuations of cytosolic Ca 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 oscillations may also spontaneously arise. Experimental studies hint that these spontaneous astrocytic Ca 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 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 exchanger (NCX), we have previously shown that NCX activity alone can generate markedly stable, spontaneous Ca 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 oscillations emerge. We also show that increased levels of intracellular astrocytic Na concentration facilitate the appearance of Ca fluctuations. These results further support the principal role of the dynamical reshaping of astrocyte processes in the generation of intrinsic Ca oscillations and their spreading over larger astrocytic compartments.