Abstract
Astroglia display a wide range of spontaneous and behavioral state-dependent Ca(2+) dynamics. During heightened vigilance, noradrenergic signaling leads to quasi-synchronous Ca(2+) elevations encompassing soma and processes across the brain-wide astroglia network. Distinct from this vigilance-associated global Ca(2+) rise are apparently spontaneous fluctuations within spatially restricted microdomains. Over the years, several strategies have been pursued to shed light on the physiological impact of these signals including deletion of endogenous ion channels or receptors and reduction of intracellular Ca(2+) through buffering, extrusion or inhibition of release. Some experiments that revealed the most compelling behavioral alterations employed chemogenetic and optogenetic manipulations to modify astroglia Ca(2+) signaling. However, there is considerable contrast between these findings and the comparatively modest effects of inhibiting endogenous sources of Ca(2+). In this review, we describe the underlying mechanisms of various forms of astroglia Ca(2+) signaling as well as the functional consequences of their inhibition. We then discuss how the effects of exogenous astroglia Ca(2+) modification combined with our knowledge of physiological mechanisms of astroglia Ca(2+) activation could guide further refinement of behavioral paradigms that will help elucidate the natural Ca(2+)-dependent function of astroglia.