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Disentangling calcium-driven astrocyte physiology

Abstract

Astrocytes seem to rely on relatively sluggish and spatially blurred Ca2+ waves to communicate with fast and point-precise neural circuits. This apparent discrepancy could, however, reflect our current inability to understand the microscopic mechanisms involved. Difficulties in detecting and interpreting astrocyte Ca2+ signals may have led to some prominent controversies in the field. Here, we argue that a deeper understanding of astrocyte physiology requires a qualitative leap in our experimental and analytical strategies.

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Figure 1: Nanoscopic physiology of brain astroglia.
Figure 2: Cellular connectivity and Ca2+ homeostasis in ultrathin astroglial protrusions.
Figure 3: The challenge of interpreting Ca2+ imaging in astroglia.

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Acknowledgements

This work was supported by the Wellcome Trust Principal Research Fellowship, the European Research Council Advanced Grant (323113 NETSIGNAL), the UK Biology and Biotechnology Sciences Research Council and the UK Medical Research Council. The author thanks K. Volynski for his help with advanced kinetic modelling software.

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Correspondence to Dmitri A. Rusakov.

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PowerPoint slides

Glossary

Ca2+ dye saturation

The scenario when nearly all Ca2+ indicator molecules are already bound to Ca2+: thus, the indicator fluorescence will be mostly insensitive to further increases in Ca2+ levels.

In silico

A theoretical experiment performed by a computer or through computer simulations.

Optical diffraction limit

The minimum size of a light spot, and thus optical resolution, at a given wavelength and light convergence angle. In conventional optics, two objects cannot be distinguished at distances smaller than the diffraction limit.

Photolytic release

A photo-stimulated (light-triggered) chemical reaction that converts a chemical compound from its inactive state into its biologically active state, often by removing a chemical 'cage'. It is also referred to as 'uncaging'.

Point-spread function

(PSF). The combined effect of diffraction-limited optics in a given imaging system.

Ratiometric Ca2+ sensors

Ca2+ indicators that shift their emission spectrum upon Ca2+ binding or unbinding; thus, the intensity ratio for the two chosen emission wavelengths provides a readout of Ca2+ concentration, which is insensitive to bleaching, focus changes or excitation intensity (but could be sensitive to scattering in organized tissue).

Steady-state approximations

Approximations of a kinetic reaction theory that can greatly simplify calculations when some of the reactions run at a much slower rate than others and therefore can be ignored when considering rapid-timescale events.

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Rusakov, D. Disentangling calcium-driven astrocyte physiology. Nat Rev Neurosci 16, 226–233 (2015). https://doi.org/10.1038/nrn3878

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