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While initial encoding involves subcortical circuits, the precise timing and necessity of neocortical engagement for remote fear memory expression remain elusive. In the present translational study from rats to humans, we identified a late consolidation phase in the medial prefrontal cortex (mPFC) that occurs around 18 h after fear conditioning, a phase essential for remote memory. Neuronal ensembles in the mPFC activated during this phase mediate the expression of remote fear memory in rats. Critically, dopaminergic signaling in the mPFC modulated by ventral tegmental area (VTA) projections specifically during this delayed phase is required for remote fear memory maintenance. Consistent with these findings in humans, non\u2010invasive stimulation of homologous mPFC regions during this temporal window selectively reduced remote fear memory retrieval without affecting recent memory. These findings reveal an evolutionarily conserved temporal window for remote fear memory and identify novel time\u2010specific targets for clinical intervention in fear\u2010 and trauma\u2010related disorders.<\/jats:p>","DOI":"10.1002\/advs.202520707","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:07:43Z","timestamp":1790780863000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Critical Time Window of Neocortex Modulation for Remote Fear Memory in Rats and Humans"],"prefix":"10.1002","author":[{"given":"Lu","family":"Cao","sequence":"first","affiliation":[{"name":"Peking University Sixth Hospital Peking University Institute of Mental Health NHC Key Laboratory of Mental Health (Peking University) National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)  Beijing People's Republic of 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