The endoplasmic reticulum in perisynaptic astrocytic processes: shape, distribution and effect on calcium activity

Abstract

Astrocytes recently emerged as key regulators of information processing in the brain. Ca2+ signals in perisynaptic astrocytic processes (PAPs) notably allow astrocytes to fine-tune neurotransmission at so-called tripartite synapses. As most PAPs are below the diffraction limit, their content in Ca2+ stores and the contribution of the latter to astrocytic Ca2+ activity is unclear. Here, we reconstruct tripartite synapses in 3D from electron microscopy and find that 75% of PAPs contain some endoplasmic reticulum (ER), a major astrocytic Ca2+ store, displaying strikingly diverse geometrical properties. To investigate the role of such spatial properties, we implemented an algorithm that creates 3D PAP meshes of various ER distributions and constant shape. Reaction-diffusion simulations in those meshes reveal that astrocyte activity is shaped by a complex interplay between the location of Ca2+ channels, Ca2+ buffering, ER shape and distribution. Overall, this study sheds new light into mechanisms regulating signal transmission in the brain.