Probabilistic encoding of stimulus strength in astrocyte global calcium signals

Astrocyte calcium signals can range in size from subcellular microdomains to waves that spread through the whole cell (and into connected cells). The differential roles of such local or global calcium signaling are under intense investigation, but the mechanisms by which local signals evolve into gl...

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Main Authors: Croft, Wayne, Reusch, Katharina, Tilunaite, Agne, Russell, Noah A., Thul, Rüdiger, Bellamy, Tomas C.
Format: Article
Published: Wiley 2016
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Online Access:https://eprints.nottingham.ac.uk/37847/
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author Croft, Wayne
Reusch, Katharina
Tilunaite, Agne
Russell, Noah A.
Thul, Rüdiger
Bellamy, Tomas C.
author_facet Croft, Wayne
Reusch, Katharina
Tilunaite, Agne
Russell, Noah A.
Thul, Rüdiger
Bellamy, Tomas C.
author_sort Croft, Wayne
building Nottingham Research Data Repository
collection Online Access
description Astrocyte calcium signals can range in size from subcellular microdomains to waves that spread through the whole cell (and into connected cells). The differential roles of such local or global calcium signaling are under intense investigation, but the mechanisms by which local signals evolve into global signals in astrocytes are not well understood, nor are the computational rules by which physiological stimuli are transduced into a global signal. To investigate these questions, we transiently applied receptor agonists linked to calcium signaling to primary cultures of cerebellar astrocytes. Astrocytes repetitively tested with the same stimulus responded with global signals intermittently, indicating that each stimulus had a defined probability for triggering a response. The response probability varied between agonists, increased with agonist concentration, and could be positively and negatively modulated by crosstalk with other signaling pathways. To better understand the processes determining the evolution of a global signal, we recorded subcellular calcium “puffs” throughout the whole cell during stimulation. The key requirement for puffs to trigger a global calcium wave following receptor activation appeared to be the synchronous release of calcium from three or more sites, rather than an increasing calcium load accumulating in the cytosol due to increased puff size, amplitude, or frequency. These results suggest that the concentration of transient stimuli will be encoded into a probability of generating a global calcium response, determined by the likelihood of synchronous release from multiple subcellular sites.
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spelling nottingham-378472020-05-04T17:44:20Z https://eprints.nottingham.ac.uk/37847/ Probabilistic encoding of stimulus strength in astrocyte global calcium signals Croft, Wayne Reusch, Katharina Tilunaite, Agne Russell, Noah A. Thul, Rüdiger Bellamy, Tomas C. Astrocyte calcium signals can range in size from subcellular microdomains to waves that spread through the whole cell (and into connected cells). The differential roles of such local or global calcium signaling are under intense investigation, but the mechanisms by which local signals evolve into global signals in astrocytes are not well understood, nor are the computational rules by which physiological stimuli are transduced into a global signal. To investigate these questions, we transiently applied receptor agonists linked to calcium signaling to primary cultures of cerebellar astrocytes. Astrocytes repetitively tested with the same stimulus responded with global signals intermittently, indicating that each stimulus had a defined probability for triggering a response. The response probability varied between agonists, increased with agonist concentration, and could be positively and negatively modulated by crosstalk with other signaling pathways. To better understand the processes determining the evolution of a global signal, we recorded subcellular calcium “puffs” throughout the whole cell during stimulation. The key requirement for puffs to trigger a global calcium wave following receptor activation appeared to be the synchronous release of calcium from three or more sites, rather than an increasing calcium load accumulating in the cytosol due to increased puff size, amplitude, or frequency. These results suggest that the concentration of transient stimuli will be encoded into a probability of generating a global calcium response, determined by the likelihood of synchronous release from multiple subcellular sites. Wiley 2016-04-30 Article PeerReviewed Croft, Wayne, Reusch, Katharina, Tilunaite, Agne, Russell, Noah A., Thul, Rüdiger and Bellamy, Tomas C. (2016) Probabilistic encoding of stimulus strength in astrocyte global calcium signals. Glia, 64 (4). pp. 537-552. ISSN 1098-1136 Astrocyte; Calcium puffs; Crosstalk; ATP; Glutamate http://dx.doi.org/10.1002/glia.22947 doi:10.1002/glia.22947 doi:10.1002/glia.22947
spellingShingle Astrocyte; Calcium puffs; Crosstalk; ATP; Glutamate
Croft, Wayne
Reusch, Katharina
Tilunaite, Agne
Russell, Noah A.
Thul, Rüdiger
Bellamy, Tomas C.
Probabilistic encoding of stimulus strength in astrocyte global calcium signals
title Probabilistic encoding of stimulus strength in astrocyte global calcium signals
title_full Probabilistic encoding of stimulus strength in astrocyte global calcium signals
title_fullStr Probabilistic encoding of stimulus strength in astrocyte global calcium signals
title_full_unstemmed Probabilistic encoding of stimulus strength in astrocyte global calcium signals
title_short Probabilistic encoding of stimulus strength in astrocyte global calcium signals
title_sort probabilistic encoding of stimulus strength in astrocyte global calcium signals
topic Astrocyte; Calcium puffs; Crosstalk; ATP; Glutamate
url https://eprints.nottingham.ac.uk/37847/
https://eprints.nottingham.ac.uk/37847/
https://eprints.nottingham.ac.uk/37847/