Significance Social interactions can bolster and protect memory performance. However, the relationship between social stimuli and individually learned memories remains enigmatic. Our work reveals that exposure to a stressed, naïve nonfamiliar conspecific or to the ambient olfactory–auditory cues of a recently stressed familiar conspecific induces reactivation of the cellular ensembles associated with a fear memory in the hippocampus. Artificially stimulating the hippocampal ensemble active during the social experience induces fearful behaviors in animals that have previously acquired a negative memory, revealing the interaction between individual history and social experience. The neural resurgence of fear-driving ensembles during social experiences leads to a context-specific enhancement of fear recall. Our findings provide evidence that unlike direct stressors, social stimuli reactivate and amplify an individual’s memories.

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 usedin vivofiber 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, 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 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.SIGNIFICANCE STATEMENT: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 impact freezing behavior or calcium dynamics. These findings show that astrocytes play a key, real-time role in fear learning and memory.

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-shocks 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 recall, and this behavior-locked pattern of activity did not persist throughout the extinction sessions. 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.

The power of one's social environment to bidirectionally modulate cognitive abilities is well documented, but the processes by which social experiences impact the cellular substrates of memory remain unknown. Here we show that social interactions and exposure to ambient stimuli emitted by stressed conspecifics, but not individually experienced physical stress, enhance the recall and reinstatement of previously acquired fear memories. Activity-dependent tagging of cells in the dentate gyrus of the hippocampus during fear learning revealed that these ensembles were endogenously reactivated during the social, but not directly stressful, experiences. These reactivated cells were revealed to be functional engrams, as optogenetic stimulation of the cells active during the social experience was sufficient to drive fear-related behaviors only in animals that had previously been fear conditioned. Our findings suggest that social encounters can reactivate pre-existing engrams and thereby strengthen discrete memories.