Temporal cortex astrocytic Gi-GPCR signaling regulates learned threat responses.

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Behavioral Neuroscience

Background:

• Astrocytes are crucial for brain circuit function, memory, and behavior.
• Astrocytic G-protein-coupled receptors (GPCRs) influence intracellular signaling and neuron-glia interactions.
• The specific roles of distinct astrocytic GPCR pathways in behavior are largely unknown.

Purpose of the Study:

• To investigate the role of astrocytic GPCR signaling in the temporal cortex, a region involved in sensory integration and fear memory.
• To determine how distinct GPCR pathways in astrocytes regulate behavioral responses, particularly fear memory retrieval.

Main Methods:

• Utilized chemogenetic tools to selectively activate specific GPCR pathways in cortical astrocytes.
• Employed *in vivo* fiber photometry to monitor astrocytic calcium (Ca2+) transients in response to sensory stimuli.
• Assessed the impact of astrocytic GPCR activation on fear memory retrieval.

Main Results:

• Selective activation of Gi-coupled GPCRs, but not Gs- or Gq-coupled GPCRs, in astrocytes enhanced fear memory retrieval.
• Temporal cortex astrocytes displayed significant Ca2+ transients in response to neutral, conditioned auditory, and aversive stimuli.
• Activation of astrocytic Gi-GPCRs attenuated cue-evoked Ca2+ transients during fear memory retrieval.

Conclusions:

• Astrocytic GPCR signaling acts as a pathway-specific regulator of fear memory retrieval.
• Astrocytic Gi-GPCR signaling modulates sensory cue processing to influence defensive behaviors.
• These findings highlight a novel mechanism by which astrocytes control fear-related behaviors.