Anterior cingulate cortex engram drives post traumatic stress disorder-like memory impairments in a rodent model of traumatic fear

Abstract

Fear memories in post-traumatic stress disorder are marked by persistent cue-driven recollection and impaired contextual recall, yet the engram organization underlying this maladaptive state remains unclear. Here we used a rodent model combining contextual fear conditioning with systemic corticosterone to mimic trauma-associated glucocorticoid exposure. This paradigm generated a PTSD-like phenotype characterized by hypermnesia for a trauma-related but irrelevant (non-predictive of the threat) cue and contextual amnesia. Activity-dependent tagging and reactivation mapping revealed that traumatic memory is supported by a regionally dysregulated engram pattern, with enhanced recruitment of the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), and reduced engagement of the dentate gyrus (DG). These changes persisted over time and correlated with the severity of the behavioral phenotype. Chemogenetic inhibition of ACC engram cells abolished traumatic memory expression, restored contextual recall, and normalized engram reactivation across DG and BLA. In contrast, inhibition of randomly tagged ACC or hippocampal populations had no such effect, indicating that the ACC engram is specifically required for traumatic memory expression. Together, these findings show that PTSD-like memory is not simply an amplified fear trace, but a distinct maladaptive engram state distributed across cortical-hippocampal- amygdalar circuits.