TEMPORAL CORTEX ASTROCYTES REGULATE LEARNED THREAT RESPONSES

Astrocytes, traditionally seen as passive support cells, are now recognized as active contributors to brain circuit function, memory processing and behavior. They express a diverse set of G-protein-coupled receptors (GPCRs) capable of modulating gliotransmitter release and the extracellular environment. However, the functional role of most astrocytic GPCRs in memory processes and behavioral regulation is still largely unknown.
Here, we investigated whether specific astrocytic GPCR signaling pathways in the cortex contribute to fear memory retrieval. Using chemogenetic tools to selectively activate distinct GPCR pathways in temporal neocortical astrocytes, we found GPCR subtype-dependent effects on fear memory retrieval. In vitro calcium imaging revealed transient astrocytic calcium elevations following chemogenetic activation of Gi and Gq-coupled receptors, resembling responses elicited by endogenous GPCR ligands. Using complementary in vivo fiber photometry experiments, we tested how sensory stimulus-driven astrocytic calcium activity changes during learning and retrieval of a classical discriminatory fear conditioning task.
Together, our results highlight astrocytic GPCR signaling as a critical component of fear memory processing in the cortex.