Abstract
Astrocytes elicit transient Ca2+ elevations induced by G protein-coupled receptors (GPCRs), yet their role in vivo remains unknown. To address this, transgenic mice with astrocytic expression of the optogenetic Gq-type GPCR, Optoα1AR, were established, in which transient Ca2+ elevations similar to those in wild type mice were induced by brief blue light illumination. Activation of cortical astrocytes resulted in an adenosine A1 receptor-dependent inhibition of neuronal activity. Moreover, sensory stimulation with astrocytic activation induced long-term depression of sensory evoked response. At the behavioral level, repeated astrocytic activation in the anterior cortex gradually affected novel open field exploratory behavior, and remote memory was enhanced in a novel object recognition task. These effects were blocked by A1 receptor antagonism. Together, we demonstrate that GPCR-triggered Ca2+ elevation in cortical astrocytes has causal impacts on neuronal activity and behavior.
Highlights
Interfacing both synapses and blood vessels, astrocytes’ prime functions in the brain have been recognized as the maintenance of extracellular environment and the transfer of energy substrates
Immunohistochemistry with astrocytic (S100β), neuronal (NeuN) and microglial (Iba1) markers showed that Optoα1AR-EYFP was expressed in astrocytes
Optogenetic activation of cortical astrocytic Gq signaling transiently inhibited local neuronal activity via the adenosine A1 receptor, induced depression of evoked response when paired with sensory stimuli, and reduced locomotor activity
Summary
Interfacing both synapses and blood vessels, astrocytes’ prime functions in the brain have been recognized as the maintenance of extracellular environment and the transfer of energy substrates. Studies in the recent decade have presented compelling evidence that astrocytes modulate neuronal activity by various mechanisms. Astrocytes sense neural activities and induce intracellular signaling via multiple ions and second messengers including Ca2+, Na2+, H+, and cAMP (Verkhratsky et al, 2020, for a review). Astrocytes elicit large-amplitude cytosolic Ca2+ elevations that are triggered by G protein-coupled receptors (GPCRs), the Gqtype, which activate the inositol trisphosphate (IP3) pathway. Amongst Gq-GPCRs, the alpha adrenergic receptor (α1AR) has been identified to be the prevalent receptor for brain-wide astrocytic Ca2+ elevations, responding to locus coeruleus (LC) activation in awake mice (Ding et al, 2013; Paukert et al, 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
