Abstract
Astrocytes exhibit spatially-restricted near-membrane microdomain Ca2+transients in their fine processes. How these transients are generated and regulate brain function in vivo remains 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 the neurotransmitter tyramine via the TyrRII receptor. Interestingly, many astrocyte microdomain Ca2+ transients are closely associated with tracheal elements, which dynamically extend filopodia throughout the central nervous system (CNS) to deliver O2 and regulate gas exchange. Many astrocyte microdomain Ca2+ transients are spatio-temporally correlated with the initiation of tracheal filopodial retraction. Loss of TrpML leads to increased tracheal filopodial numbers, growth, and increased CNS ROS. We propose that local ROS production can activate astrocyte microdomain Ca2+ transients through TrpML, and that a subset of these microdomain transients promotes tracheal filopodial retraction and in turn modulate CNS gas exchange.
Highlights
Astrocytes exhibit two major types of Ca2+ signaling events, whole-cell fluctuations and near-membrane microdomain Ca2+ transients (Khakh and McCarthy, 2015)
Blockade of action potential firing with tetrodotoxin did not alter astrocyte microdomain Ca2+ transients, they were eliminated by removal of extracellular Ca2+ and were sensitive to the Ca2+ channel blocker lanthanum chloride (LaCl3) (Figure 1D), suggesting Ca2+ entry from extracellular space is essential for generation of astrocyte microdomain Ca2+ transients
Molecules required for the generation of astrocyte microdomain Ca2+ transients have remained elusive, it remains unclear how many ‘types’ of microdomain Ca2+transients exist in astrocytes, and the in vivo roles for these transients remain controversial and poorly defined (Agarwal et al, 2017; Bazargani and Attwell, 2016)
Summary
Astrocytes exhibit two major types of Ca2+ signaling events, whole-cell fluctuations and near-membrane microdomain Ca2+ transients (Khakh and McCarthy, 2015). Whole-cell transients are coordinated across astrocyte networks and regulated by adrenergic receptor signaling. Octopamine and tyramine stimulate cell-wide astrocyte Ca2+ increase through the dualspecificity Octopamine-Tyramine Receptor (Oct-TyrR) and the TRP channel Water witch (Wtrw) This astrocyte-mediated signaling event downstream of octopamine and tyramine is critical for in vivo neuromodulation: astrocyte-specific elimination of Oct-TyrR or Wtrw in larvae blocks the ability of octopamine and tyramine to silence downstream dopaminergic neurons, and alters both simple chemosensory behavior and a touch-induced startle response (Ma et al, 2016). We propose that one in vivo role for tracheal–astrocyte interactions is to regulate CNS gas exchange, with tracheal filopodia-dependent local hyperoxia resulting in increased production of ROS, which gates TrpML to generate local astrocyte microdomain Ca2+ transients, promoting tracheal retraction and reducing local O2 delivery
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