Unraveling ChR2-driven stochastic Ca2+ dynamics in astrocytes: A call for new interventional paradigms

• DOI: 10.1371/journal.pcbi.1008648
• Publication Date: 2021-02-10T20:02:03Z
• Authors: Arash Moshkforoush; Lakshmini Balacha...; Carolina Moncion; Karla A. Montejo; Jorge Riera
• Keywords: Channelrhodopsin; Nerve net; Calcium imaging

Optogenetic targeting of astrocytes provides a robust experimental model to differentially induce Ca 2+ signals in vivo . However, systematic study quantifying the response optogenetically modified light is yet be performed. Here, we propose novel stochastic dynamics that incorporates sensitive component—channelrhodopsin 2 (ChR2). Utilizing this model, investigated effect different stimulation paradigms on cells expressing select variants ChR2 (wild type, ChETA, and ChRET/TC). Results predict depending paradigm specification, might undergo drastic changes their basal level spiking probability. Furthermore, performed global sensitivity analysis assess variation parameters pertinent shape photocurrent astrocytic dynamics. suggest directing towards first open state photocycle (o 1 ) enhances activity during optical stimulation. Evaluation buffering coupling coefficient network ChR2-expressing demonstrated elevations stimulated region propagation calcium unstimulated cells. Buffering reduced diffusion range within network, thereby limiting influencing astrocytes. Collectively, framework presented valuable information for selection elicit desired using existing constructs, as well aids engineering future application-oriented optogenetic variants.