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

• Published in: The Journal of neuroscience 2023-07, Vol.43 (27), p.4997-5013
• Main Authors: Suthard, Rebecca L, Senne, Ryan A, Buzharsky, Michelle D, Pyo, Angela Y, Dorst, Kaitlyn E, Diep, Anh H, Cole, Rebecca H, Ramirez, Steve
• Format: Article
• Language: English
• Subjects: Amygdala; Animals; Astrocytes; Basolateral Nuclear Complex - physiology; Calcium; Calcium signalling; Cognition; Conditioning (learning); Extinction behavior; Extinction, Psychological - physiology; Fear; Fear - physiology; Fear conditioning; Footshock; In vivo methods and tests; Learning; Male; Memory; Mice; Mice, Inbred C57BL; Photometry; Recall; Species extinction; Tonic immobility
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1775-22.2023

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 fiber photometry in C57BL/6J male mice 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, their activity remained remarkably elevated across days in comparison to unshocked control animals, and 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 specific to the original fear-associated environment. 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. We show that basolateral amygdala astrocytes are robustly responsive to negative experiences, like shock, and display changed calcium activity patterns through fear learning and memory. Additionally, astrocytic calcium responses become time locked to the initiation and termination of freezing behavior during fear learning and recall. We find that astrocytes display calcium dynamics unique to a fear-conditioned context, and chemogenetic inhibition of BLA fear ensembles does not have an impact on freezing behavior or calcium dynamics. These findings show that astrocytes play a key real-time role in fear learning and memory.