Probabilistic encoding of stimulus strength in astrocyte global calcium signals

Croft, Wayne; Reusch, Katharina; Tilunaite, Agne; Russell, Noah A.; Thul, R�diger; Bellamy, Tomas C.

Abstract

© 2016 Wiley Periodicals, Inc. 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.

Citation

Croft, W., Reusch, K., Tilunaite, A., Russell, N. A., Thul, R., & Bellamy, T. C. (2016). Probabilistic encoding of stimulus strength in astrocyte global calcium signals. Glia, 64(4), 537-552. https://doi.org/10.1002/glia.22947

• Journal Article Type: Article
• Acceptance Date: Nov 16, 2015
• Online Publication Date: Dec 9, 2015
• Publication Date: Apr 1, 2016
• Deposit Date: Oct 24, 2016
• Publicly Available Date: Oct 24, 2016
• Journal: Glia
• Print ISSN: 0894-1491
• Electronic ISSN: 1098-1136
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 64
• Issue: 4
• Pages: 537-552
• DOI: https://doi.org/10.1002/glia.22947
• Keywords: Astrocyte; Calcium puffs; Crosstalk; ATP; Glutamate
• Public URL: https://nottingham-repository.worktribe.com/output/782977
• Publisher URL: http://dx.doi.org/10.1002/glia.22947
• Additional Information: This is the peer reviewed version of the following article: Croft, W., Reusch, K., Tilunaite, A., Russell, N. A., Thul, R. and Bellamy, T. C. (2016), Probabilistic encoding of stimulus strength in astrocyte global calcium signals. Glia, 64: 537–552, which has been published in final form at http://dx.doi.org/10.1002/glia.22947. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.