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Here, using a mouse model of PTSD induced by inescapable footshock, we observed a delayed and prolonged increase in avoidance behavior associated with selective activation of basolateral amygdala (BLA) projection neurons (PNs) targeting ventral hippocampus (BLA\u2192vHPC PNs), but not nucleus accumbens, in both sexes. This projection-specific activation results from enhanced neuronal excitability and excitatory transmission driven by glucocorticoid receptor (GR) signaling. Among the cascade of GR signaling molecules, we identified serum- and glucocorticoid-regulated kinase 1 (Sgk1) as a key downstream mediator linking stress exposure to the hyperactivation of BLA\u2192vHPC PNs and PTSD-like avoidance behavior. Manipulating Sgk1 expression bidirectionally regulates neuronal activity and susceptibility to stress-induced avoidance. These findings underscore the critical role of projection-specific upregulation of Sgk1 in BLA PNs in the pathogenesis of PTSD-like avoidance behavior.<\/jats:p>","DOI":"10.1038\/s41467-026-71129-0","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T03:35:25Z","timestamp":1775014525000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sgk1 upregulation in hippocampus-projecting amygdala neurons underlies the delayed onset of PTSD-like avoidance behavior"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9309-5827","authenticated-orcid":false,"given":"Jia-Xin","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Zhu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2326-6206","authenticated-orcid":false,"given":"Ya-Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jie","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Qing","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0230-9856","authenticated-orcid":false,"given":"Wen-Hua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-4019","authenticated-orcid":false,"given":"Bing-Xing","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"71129_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.neuron.2007.09.006","volume":"56","author":"R Yehuda","year":"2007","unstructured":"Yehuda, R. & LeDoux, J. 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