Fig. 1. Optogenetic and chemogenetic stimulation of astrocytes. A variety of genetically encoded effector molecules for optogenetics (left) and chemogenetics (right) have been employed to manipulate intracellular ionic concentrations (H+, Na+, Ca2+, K+) and signaling cascades (Gq, Gs, DAG, IP3, cAMP) in astrocytes. Intracellular changes such as cytosolic calcium increase and acidification, in turn, evoke release of signaling molecules, so-called gliotransmitters (glutamate, ATP, L-lactate), from astrocytes, which modulate excitability as well as synaptic transmission of neighboring neurons. Optogenetic effectors can be activated by specific wavelengths of photostimulation, and chemogenetic effectors can be activated by synthetic ligands, such as CNO. ChR2, channelrhodopsin-2; CatCh, calcium translocating channelrhodopsin; LiGluR, light-gated ionotropic glutamate receptor 6; ArchT, archaerhodopsin; OptoXRs, light-driven chimeric G protein-coupled receptors; NMDAR, N-methyl-D-aspartate receptor; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; Gi-DREADD, Gi-coupled designer receptors exclusively activated by designer drugs; Gq-DREADD, Gq-coupled DREADD; Gs-DREADD, Gs-coupled DREADD; CNO, clozapine-N-oxide; ATP, adenosine triphosphate; IP3, inositol 1,4,5-trisphosphate; DAG, diacylglycerol; cAMP, cyclic adenosine monophosphate.
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