Open AccessUnraveling ChR2-driven stochastic Ca2+ dynamics in astrocytes: A call for new interventional paradigms
Author(s) -
Arash Moshkforoush,
Lakshmini Balachandar,
Carolina Moncion,
Karla A. Montejo,
Jorge J. Riera
Publication year - 2021
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1008648
Subject(s) - optogenetics , channelrhodopsin , astrocyte , neuroscience , stimulation , nerve net , calcium imaging , premovement neuronal activity , biological system , computer science , biology , biophysics , calcium , chemistry , central nervous system , organic chemistry
Optogenetic targeting of astrocytes provides a robust experimental model to differentially induce Ca 2+ signals in astrocytes in vivo . However, a systematic study quantifying the response of optogenetically modified astrocytes to light is yet to be performed. Here, we propose a novel stochastic model of Ca 2+ dynamics in astrocytes that incorporates a light sensitive component—channelrhodopsin 2 (ChR2). Utilizing this model, we investigated the effect of different light stimulation paradigms on cells expressing select variants of ChR2 (wild type, ChETA, and ChRET/TC). Results predict that depending on paradigm specification, astrocytes might undergo drastic changes in their basal Ca 2+ level and spiking probability. Furthermore, we performed a global sensitivity analysis to assess the effect of variation in parameters pertinent to the shape of the ChR2 photocurrent on astrocytic Ca 2+ dynamics. Results suggest that directing variants towards the first open state of the ChR2 photocycle (o 1 ) enhances spiking activity in astrocytes during optical stimulation. Evaluation of the effect of Ca 2+ buffering and coupling coefficient in a network of ChR2-expressing astrocytes demonstrated basal level elevations in the stimulated region and propagation of calcium activity to unstimulated cells. Buffering reduced the diffusion range of Ca 2+ within the network, thereby limiting propagation and influencing the activity of astrocytes. Collectively, the framework presented in this study provides valuable information for the selection of light stimulation paradigms that elicit desired astrocytic activity using existing ChR2 constructs, as well as aids in the engineering of future application-oriented optogenetic variants.