AGE-DEPENDENT EFFECTS OF EARLY-LIFE STRESS ON BLA NEURAL ENSEMBLES ENCODING INNATE BEHAVIORS

Memories are encoded to sparse neuronal ensembles that are reactivated during memory retrieval. Stress-induced alterations in the properties of fear-encoding ensembles have been implicated in anxiety-related phenotypes, including threat overgeneralization. Early-life stress (ELS) increases vulnerability to psychiatric disorders; however, how ELS affects ensembles related to innate behaviors remains poorly understood. Here, we used a limited bedding and nesting (LBN) protocol combined with maternal separation to model ELS in mice. Using the TRAP2 mouse line, we tagged neurons activated during bright open field exposure at P22 and examined the density, reactivation, and excitability of these cells in the basolateral amygdala (BLA) in juvenile (P29) and adult (P60) stages using immunohistochemistry and whole-cell patch-clamp recordings. Our results indicate that ELS affects neuronal activation during innate behaviours, indicated by lower density of tagged cells compared to the control group. In juvenile mice, the excitability of tagged neurons in the ELS group was lower than in controls, with more pronounced effects in females. These differences evened out or reversed towards adulthood, in parallel with development of amygdala hyper-reactivity. Interestingly, while re-activation of the tagged neurons during the same behavior was reduced during development in control mice, high levels of re-activation were maintained in the ELS group. Together, these findings suggest that ELS influences the properties of innate behavior-activated neuronal ensembles in the amygdala in age-specific manner, with potential relevance for advancing our understanding on how early adversity shapes neuronal populations involved in emotional behavior throughout life.