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We show here that induction of the transcription factor \u0394FosB in mPFC, specifically in the prelimbic (PrL) area, mediates susceptibility to stress. \u0394FosB induction in PrL occurred selectively in susceptible mice after chronic social defeat stress, and overexpression of \u0394FosB in this region, but not in the nearby infralimbic (IL) area, enhanced stress susceptibility. \u0394FosB produced these effects partly through induction of the cholecystokinin (CCK)-B receptor: CCKB blockade in mPFC induces a resilient phenotype, whereas CCK administration into mPFC mimics the anxiogenic- and depressant-like effects of social stress. We previously found that optogenetic stimulation of mPFC neurons in susceptible mice reverses several behavioral abnormalities seen after chronic social defeat stress. Therefore, we hypothesized that optogenetic stimulation of cortical projections would rescue the pathological effects of CCK in mPFC. After CCK infusion in mPFC, we optogenetically stimulated mPFC projections to basolateral amygdala or nucleus accumbens, two subcortical structures involved in mood regulation. Stimulation of corticoamygdala projections blocked the anxiogenic effect of CCK, although no effect was observed on other symptoms of social defeat. Conversely, stimulation of corticoaccumbens projections reversed CCK-induced social avoidance and sucrose preference deficits but not anxiogenic-like effects. Together, these results indicate that social stress-induced behavioral deficits are mediated partly by molecular adaptations in mPFC involving \u0394FosB and CCK through cortical projections to distinct subcortical targets.<\/jats:p>","DOI":"10.1523\/jneurosci.1787-13.2014","type":"journal-article","created":{"date-parts":[[2014,3,12]],"date-time":"2014-03-12T13:44:44Z","timestamp":1394631884000},"page":"3878-3887","source":"Crossref","is-referenced-by-count":296,"title":["Prefrontal Cortical Circuit for Depression- and Anxiety-Related Behaviors Mediated by Cholecystokinin: Role of \u0394FosB"],"prefix":"10.1523","volume":"34","author":[{"given":"Vincent","family":"Vialou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary C.","family":"Bagot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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