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  • Review Article
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Making sense of astrocytic calcium signals — from acquisition to interpretation

Abstract

Astrocytes functionally interact with neurons and with other brain cells. Although not electrically excitable, astrocytes display a complex repertoire of intracellular Ca2+ signalling that evolves in space and time within single astrocytes and across astrocytic networks. Decoding the physiological meaning of these dynamic changes in astrocytic Ca2+ activity has remained a major challenge. This Review describes experimental preparations and methods for recording and studying Ca2+ activity in astrocytes, focusing on the analysis of Ca2+ signalling events in single astrocytes and in astrocytic networks. The limitations of existing experimental approaches and ongoing technical and conceptual challenges in the interpretation of astrocytic Ca2+ events and their spatio-temporal patterns are also discussed.

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Fig. 1: Visualization of astrocytic Ca2+ signals.
Fig. 2: Spatio-temporal analysis of astrocytic Ca2+ activity.
Fig. 3: Signal processing in astrocytes and neurons.
Fig. 4: Different levels of interaction between neurons and astrocytes.

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Acknowledgements

The research work of A.S.’s laboratory is supported by Russian Science Foundation grant 20-14-00241. The research work of A.A.’s laboratory is supported by the Chica and Heinz Schaller Research Foundation, the Brain & Behaviour Research Foundation via a National Alliance for Research on Schizophrenia & Depression (NARSAD) Young Investigator Award and grants from the Deutsche Forschungsgemeinschaft (DFG): SFB1134-B01, SFB1158-A09 and FOR2289-P8. C.H.’s laboratory is supported by DFG grants SFB1089 B03, SPP1757 HE6949/1, FOR2795 and HE6949/3.

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Glossary

Deconvolution-based techniques

Deconvolution (reversing the inherent image distortion specific to a given microscope or other imaging instrument) is usually done by image-processing software as part of image generation.

Schaffer collaterals

Axon collaterals derived from CA3 pyramidal cells that project to hippocampal area CA1. Schaffer collaterals influence learning and memory via activity-dependent plasticity and are integral to hippocampal medial limbic and trisynaptic circuits.

InsP3 sponge

A recombinant peptide including modified ligand-binding domains from mouse inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1), designed to sequester intracellular InsP3 owing to its ~1,000-fold higher affinity for InsP3 than for native IP3Rs.

APP/PS1 mice

A double-transgenic mouse model of Alzheimer disease that expresses both chimeric (mouse–human) amyloid precursor protein (APP) and mutant human presenilin 1 (PS1) specifically in CNS neurons.

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Semyanov, A., Henneberger, C. & Agarwal, A. Making sense of astrocytic calcium signals — from acquisition to interpretation. Nat Rev Neurosci 21, 551–564 (2020). https://doi.org/10.1038/s41583-020-0361-8

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