Control of Ca 2+ signals by astrocyte nanoscale morphology at tripartite synapses

Audrey Denizot, Misa Arizono, U. Valentin Nägerl, Hugues Berry, Erik De Schutter
Glia. 2022-09-13; :
DOI: 10.1002/glia.24258

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Denizot A(1), Arizono M(2)(3)(4), Nägerl UV(2)(3), Berry H(5)(6), De Schutter E(1).

Author information:
(1)Computational Neuroscience Unit, Okinawa Institute of Science and Technology,
Onna-Son, Japan.
(2)Interdisciplinary Institute for Neuroscience, Université de Bordeaux,
Bordeaux, France.
(3)Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
(4)Department of Pharmacology, Kyoto University Graduate School of Medicine,
Kyoto, Japan.
(5)LIRIS, UMR5205 CNRS, Univ Lyon, Villeurbanne, France.
(6)INRIA, Villeurbanne, France.

Much of the Ca2+ activity in astrocytes is spatially restricted to microdomains
and occurs in fine processes that form a complex anatomical meshwork, the
so-called spongiform domain. A growing body of literature indicates that those
astrocytic Ca2+ signals can influence the activity of neuronal synapses and thus
tune the flow of information through neuronal circuits. Because of technical
difficulties in accessing the small spatial scale involved, the role of astrocyte
morphology on Ca2+ microdomain activity remains poorly understood. Here, we use
computational tools and idealized 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
so-called tripartite synapses, where astrocytic processes come into close contact
with pre- and postsynaptic structures.

© 2022 The Authors. GLIA published by Wiley Periodicals LLC.


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