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Data from our laboratory suggested that adolescent C57BL\/6J and DBA\/2J inbred mice differed in susceptibility to alcohol\u2010induced deficits in dorsal hippocampus\u2010dependent contextual fear learning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression using RNA\u2010sequencing after alcohol or saline administration followed by Pavlovian fear conditioning across male and female C57BL\/6J and DBA\/2J adolescents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Strains exhibited dramatic differences in dorsal hippocampus gene expression. Specifically, C57BL\/6J and DBA\/2J strains differed by 3526 transcripts in males and 2675 transcripts in females. We identified pathways likely to be involved in mediating alcohol's effects on learning, including networks associated with <jats:italic>Chrna7<\/jats:italic>, a gene encoding the nicotinic cholinergic receptor alpha 7 subunit, and <jats:italic>Fmr1<\/jats:italic>, a gene encoding the fragile X messenger ribonucleoprotein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings provide insight into the mechanisms underlying strain differences in alcohol's effects on learning and suggest that different biological networks are recruited for learning based on genetics, sex, and alcohol exposure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15440","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T08:59:31Z","timestamp":1726477171000},"page":"2022-2034","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alcohol and fear conditioning produce strain\u2010specific changes in the dorsal hippocampal transcriptome of adolescent <scp>C57BL<\/scp>\/<scp>6J<\/scp> and <scp>DBA<\/scp>\/<scp>2J<\/scp> mice"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1534-5357","authenticated-orcid":false,"given":"Laurel R.","family":"Seemiller","sequence":"first","affiliation":[{"name":"Department of Biobehavioral Health Penn State University  University Park Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa R.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Biobehavioral Health Penn State University  University Park Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aswathy","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Huck Institutes of the Life Sciences Penn State University  University Park Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue 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