title: Probabilistic encoding of stimulus strength in astrocyte global calcium signals.
abstract: 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.
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Wayne
authors.initials: W
authors.lastname: Croft
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.|Department of Electrical and Electronic Engineering, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Katharina
authors.initials: K
authors.lastname: Reusch
authors.affiliation: School of Mathematical Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Agne
authors.initials: A
authors.lastname: Tilunaite
authors.affiliation: Department of Electrical and Electronic Engineering, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Noah A
authors.initials: NA
authors.lastname: Russell
authors.affiliation: School of Mathematical Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Thul
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Tomas C
authors.initials: TC
authors.lastname: Bellamy
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D048588:Benzoxazines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D011336:Probability; D051381:Rats; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D048588:Benzoxazines; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D009025:Morpholines; D009281:Naphthalenes; D018698:Glutamic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D006632:Histamine; D000255:Adenosine Triphosphate; D005682:Gadolinium; D002118:Calcium
keywords: ATP; astrocyte; calcium puffs; crosstalk; glutamate