Transient astrocytic Gq signaling underlies remote memory enhancement

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. On the other hand, compelling evidence for astrocytic Ca²⁺-induced diameter changes of arteries was not observed. Together, we demonstrate that GPCR-triggered Ca²⁺ elevation in cortical astrocytes has causal impacts on neuronal activity and behavior.