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The prelimbic (PrL) cortex is vulnerable to insult from adolescent alcohol exposure and receives input from the basolateral amygdala (BLA) while sending projections to the ventrolateral periaqueductal gray (vlPAG) \u2013 two brain regions implicated in nociception. In this study, adolescent intermittent ethanol (AIE) exposure was carried out in male and female rats using a vapor inhalation procedure. Assessments of mechanical and thermal sensitivity revealed that AIE exposure-induced protracted mechanical allodynia. To investigate synaptic function at BLA inputs onto defined populations of PrL neurons, retrobeads and viral labeling were combined with optogenetics and slice electrophysiology. Recordings from retrobead labeled cells in the PrL revealed AIE reduced BLA-driven feedforward inhibition of neurons projecting from the PrL to the vlPAG, resulting in augmented excitation\/inhibition (E\/I) balance and increased intrinsic excitability. Consistent with this finding, recordings from virally tagged PrL parvalbumin interneurons (PVINs) demonstrated that AIE exposure reduced both E\/I balance at BLA inputs onto PVINs and PVIN intrinsic excitability. These findings provide compelling evidence that AIE alters synaptic function and intrinsic excitability within a prefrontal nociceptive circuit.<\/jats:p>","DOI":"10.7554\/elife.101667","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T08:25:14Z","timestamp":1732523114000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.101667","source":"Crossref","is-referenced-by-count":7,"title":["Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7526-4869","authenticated-orcid":true,"given":"J Daniel","family":"Obray","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012jban78","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Medical University of South Carolina","place":["Charleston, United 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