TrpML-mediated astrocyte microdomain Ca2+ transients regulate astrocyte-tracheal interactions in CNS

Astrocytes exhibit spatially-restricted near membrane microdomain Ca2+ transients in their fine processes. How these transients are generated, and how they regulate brain function in vivo remain unclear. Here we show that Drosophila astrocytes exhibit spontaneous, activity-independent microdomain Ca2+ transients in their fine processes. Astrocyte microdomain Ca2+ transients are mediated by the TRP channel TrpML, stimulated by reactive oxygen species (ROS),and can be enhanced in frequency by tyramine (Tyr) via the TyrRII receptor. Interestingly, astrocyte microdomain Ca2+ transients are closely associated with tracheal elements, which dynamically extend filopodia throughout the nervous system, and astrocyte microdomain Ca2+ transients precede retraction of tracheal filopodia. Loss of TrpML leads to increased tracheal filopodial numbers and growth, and increased ROS in the CNS. Basal levels of astrocyte microdomain Ca2+ transients were regulated by the hypoxia-sensitive factor Sima/Hif-1α, providing a link between astrocyte-tracheal interactions and the molecular control of CNS gas exchange. We propose that local ROS production regulates tracheal dynamics through TrpML-dependent modulation of astrocyte microdomain Ca2+ transients, and in turn CNS gas exchange.