Abstract
Astroglia display a wide range of spontaneous and behavioral state-dependent Ca2+ dynamics. During heightened vigilance, noradrenergic signaling leads to quasi-synchronous Ca2+ elevations encompassing soma and processes across the brain-wide astroglia network. Distinct from this vigilance-associated global Ca2+ 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 Ca2+ through buffering, extrusion or inhibition of release. Some experiments that revealed the most compelling behavioral alterations employed chemogenetic and optogenetic manipulations to modify astroglia Ca2+ signaling. However, there is considerable contrast between these findings and the comparatively modest effects of inhibiting endogenous sources of Ca2+. In this review, we describe the underlying mechanisms of various forms of astroglia Ca2+ signaling as well as the functional consequences of their inhibition. We then discuss how the effects of exogenous astroglia Ca2+ modification combined with our knowledge of physiological mechanisms of astroglia Ca2+ activation could guide further refinement of behavioral paradigms that will help elucidate the natural Ca2+-dependent function of astroglia.
Highlights
Function and BehaviorAchucarro Basque Center for Neuroscience, Spain J
Astroglia are ubiquitous in the brain and exhibit a range of morphological structure adapted for each brain region
Proteins are described in terms of the following: biological function; proven or expected dependence on IP3R2; whether experiments were conducted in vivo and if so, whether done in awake or anesthetized mice; and whether the Ca2+ signal is behavior-induced and if so, whether this was validated in awake or anesthetized mice. #, indicates proteins for which functional expression in astroglia has been demonstrated by conditional gene deletion or rescue, and the respective studies are indicated individually. *, “Behavior-induced” indicates that a Ca2+ signal is caused by any form of sensory stimulation or awake behavior
Summary
Achucarro Basque Center for Neuroscience, Spain J. Astroglia display a wide range of spontaneous and behavioral state-dependent Ca2+ dynamics. Noradrenergic signaling leads to quasisynchronous Ca2+ elevations encompassing soma and processes across the brainwide astroglia network. Distinct from this vigilance-associated global Ca2+ rise are apparently spontaneous fluctuations within spatially restricted microdomains. We describe the underlying mechanisms of various forms of astroglia Ca2+ signaling as well as the functional consequences of their inhibition. We discuss how the effects of exogenous astroglia Ca2+ modification combined with our knowledge of physiological mechanisms of astroglia Ca2+ activation could guide further refinement of behavioral paradigms that will help elucidate the natural Ca2+-dependent function of astroglia
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