Basolateral Amygdala Astrocytes Are Engaged by the Acquisition and Expression of a Contextual Fear Memory

Abstract Astrocytes are key cellular regulators within the brain. The basolateral amygdala (BLA) is implicated in fear memory processing, yet most research has entirely focused on neuronal mechanisms, despite a significant body of work implicating astrocytes in learning and memory. In the present study, we used in vivo fiber photometry to record from amygdalar astrocytes across fear learning, recall, and three separate periods of extinction. We found that BLA astrocytes robustly responded to foot shock during acquisition, that their activity remained remarkably elevated across days in comparison to unshocked control animals, and that their increased activity persisted throughout extinction. Further, we found that astrocytes responded to the initiation and termination of freezing bouts during contextual fear conditioning and recall, and this behavior-locked pattern of activity did not persist throughout the extinction sessions. Importantly, astrocytes do not display these changes while exploring a novel context, suggesting that these observations are context or memory-dependent. Chemogenetic inhibition of fear ensembles in the BLA did not affect freezing behavior or astrocytic calcium dynamics. Overall, our work presents a real-time role for amygdalar astrocytes in fear processing and provides new insight into the emerging role of these cells in cognition and behavior. Significance Statement We show that basolateral amygdala astrocytes are robustly responsive to footshock, exhibit unique calcium event characteristics following contextual fear acquisition, and ramp up activity at the initiation and termination of freezing bouts during fear conditioning and recall. This astrocytic calcium response to freezing behavior is not observed during extinction sessions, despite unique calcium events continuing through three days of training compared to no-shock controls. We find that astrocytes display context specific changes in calcium signaling, but chemogenetic inhibition of BLA fear ensembles does not impact freezing behavior or calcium dynamics. These findings show that astrocytes play a key, real-time role in fear learning and memory.