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The central amygdala (CeA), a key brain region for pain, threat-detection, autonomic engagement, and valence assignment, is active during opioid withdrawal. However, the role of molecularly distinct CeA neural populations in withdrawal remains underexplored. Here, we investigated the activity dynamics, brain-wide connectivity, and functional contribution of Protein Kinase C-delta (PKC\u03b4)-expressing neurons in the CeA lateral capsule (CeLC\n                    <jats:sup>PKC\u03b4<\/jats:sup>\n                    ) during fentanyl withdrawal in mice. Mapping activity-dependent gene expression in CeLC\n                    <jats:sup>PKC\u03b4<\/jats:sup>\n                    neurons revealed a highly withdrawal-active subregion in the anterior half of the CeA. Fiber photometry calcium imaging showed that opioid-na\u00efve CeLC\n                    <jats:sup>PKC\u03b4<\/jats:sup>\n                    neurons respond to salient noxious and startling stimuli. In fentanyl-dependent mice, naloxone-precipitated withdrawal increased spontaneous neural activity and enhanced responses to noxious stimuli. Chronic inhibition of CeLC\n                    <jats:sup>PKC\u03b4<\/jats:sup>\n                    neurons throughout fentanyl exposure, via viral overexpression of the potassium channel Kir2.1, attenuated withdrawal symptoms in fentanyl-dependent mice. Lastly, we identified putative opioid-sensitive inputs to CeLC\n                    <jats:sup>PKC\u03b4<\/jats:sup>\n                    neurons using rabies-mediated monosynaptic circuit tracing and color-switching tracers to map mu-opioid receptor-expressing inputs to the CeLC. Collectively, these findings suggest that the hyperactivity of CeLC\n                    <jats:sup>PKC\u03b4<\/jats:sup>\n                    neurons underlies the somatic signs of fentanyl withdrawal, offering new insights into the amygdala cell-types and circuits involved in opioid dependence.\n                  <\/jats:p>","DOI":"10.1038\/s41386-025-02298-7","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:28:47Z","timestamp":1766154527000},"page":"1110-1122","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Central amygdalar PKC\u03b4 neurons mediate fentanyl withdrawal"],"prefix":"10.1038","volume":"51","author":[{"given":"Lisa M.","family":"Wooldridge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5179-0964","authenticated-orcid":false,"given":"Jacqueline W. 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