P2.77 CHRONIC ACTIVATION OF A SAFETY ENGRAM DURING DEVELOPMENT IMPROVES FEAR REGULATION IN ADULTHOOD
Hannah Burnell, Madison Soares, Surina Prabhu, Surabhi Bhaskar, Heidi Meyer
Boston University, Boston, USA
Advisor: Heidi Meyer, Principal Investigator
Assistant Professor, Boston University
Department of Psychological and Brain Sciences
Center for Systems Neuroscience
Neurophotonics Center
Abstract Body
Adolescence is a sensitive window of neurodevelopment during which experiences can have lasting effects on cognition and behavior. In particular, plasticity in the neural circuits that process fear opens up a period during which experiences can shape later responses to threat and stress.
Here, we tested whether driving an experience through adolescence improves fear regulation in adulthood. Mice were trained to discriminate between a fear cue (tone paired with footshock) and a safety cue (second tone, never paired with shock). Using a knock-in mouse for activity-dependent genetic labeling (TRAP2), we tagged a neuronal ensemble active during the safety cue (safety engram), then chronically reactivated this safety engram across adolescence and the transition into adulthood (postnatal days 35 to 69) using an excitatory chemogenetic approach.
Behavioral testing in adulthood revealed no significant differences in behavior across anxiety- and depressive-like tests (elevated plus maze, marble burying, tail suspension, and novelty suppressed feeding). Conversely, developmental reactivation significantly reduced cued fear in adulthood. Freezing to the previously conditioned fear cue was lower during both a summation test for conditioned inhibition and fear extinction. Furthermore, developmental reactivation accelerated fear extinction. Ongoing work is evaluating the impact of safety engram reactivation on structural connectivity between the hippocampus and prefrontal cortex.
These findings suggest that reactivating hippocampal safety ensembles during adolescence can enhance long-term cued fear regulation without altering affective behavior broadly. This informs the potential to leverage developmental windows to promote adaptive emotional regulation strategies throughout the lifespan.
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