AMYGDALAR MODULATION OF HIPPOCAMPAL FEAR MEMORY ENGRAMS ACROSS SEXES

Chronic hyperactivity of the amygdala is a hallmark of anxiety-related disorders, yet its effects on hippocampal memory circuits and engram dynamics are not fully understood. Here, we examined how sustained hyperactivation of the right basolateral amygdala (BLA) influences dentate gyrus (DG) engram reactivation using the Robust Activity Marking (RAM) system to label and track memory-encoding neuronal ensembles. Using chemogenetic stimulation, we observed that prolonged right BLA activation impairs context discrimination in both male and female mice. At the cellular level, chronic right BLA hyperactivation elevated c-Fos expression throughout the amygdala in both sexes, as well as in the DG and CA3, indicating coordinated activation of hippocampal circuits. These alterations were accompanied by sex-specific consequences: female mice exhibited increased anxiety-like behaviors and locomotor hyperactivity, whereas male mice showed impaired DG engram reactivation in ambiguous contexts, reflecting a selective reduction in memory precision without overt anxiety. Collectively, these results demonstrate that persistent right amygdala hyperactivity in adulthood is sufficient to drive circuit-level maladaptations characteristic of anxiety disorders and critically modulates DG engram function in a sex-dependent manner. This study underscores the role of right amygdala dysfunction in compromising memory specificity and offers new insights into how amygdalo–hippocampal interactions drive maladaptive memory processing in anxiety-related disorders.