Control of Ca2+ signals by astrocyte nanoscale morphology at tripartite synapses

Abstract

AbstractAstrocytic Ca2+ signals regulate synaptic activity. Most of those signals are spatially restricted to microdomains and occur in fine processes that cannot be resolved by diffraction-limited light microscopy, restricting our understanding of their physiology. Those fine processes are characterized by an elaborate morphology, forming the so-called spongiform domain, which could, similarly to dendritic spines, shapes local Ca2+ dynamics. Because of the technical limitations to access the small spatial scale involved, the effect of astrocyte morphology on Ca2+ microdomain activity remains poorly understood. Here, we use computational tools and realistic 3D geometries of fine processes based on recent super-resolution microscopy data to investigate the mechanistic link between astrocytic nanoscale morphology and local Ca2+ activity. Simulations demonstrate that the nano-morphology of astrocytic processes powerfully shapes the spatio-temporal properties of Ca2+ signals and promotes local Ca2+ activity. The model predicts that this effect is attenuated upon astrocytic swelling, hallmark of brain diseases, which we confirm experimentally in hypo-osmotic conditions. Upon repeated neurotransmitter release events, the model predicts that swelling hinders astrocytic signal propagation. Overall, this study highlights the influence of the complex morphology of astrocytes at the nanoscale and its remodeling in pathological conditions on neuron-astrocyte communication at tripartite synapses.