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Mem."],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>The absence of \u03b12* nicotinic acetylcholine receptors (nAChRs) in oriens lacunosum moleculare (OLM) GABAergic interneurons ablate the facilitation of nicotine-induced hippocampal CA1 long-term potentiation and impair memory. The current study delineated whether genetic mutations of \u03b12* nAChRs (<jats:italic>Chrna2<\/jats:italic><jats:sup>L9\u2032S\/L9\u2032S<\/jats:sup>and<jats:italic>Chrna2<\/jats:italic><jats:sup>KO<\/jats:sup>) influence hippocampus-dependent learning and memory and CA1 synaptic plasticity. We substituted a serine for a leucine (L9\u2032S) in the \u03b12 subunit (encoded by the<jats:italic>Chrna2<\/jats:italic>gene) to make a hypersensitive nAChR. Using a dorsal hippocampus-dependent task of preexposure-dependent contextual fear conditioning, adolescent hypersensitive<jats:italic>Chrna2<\/jats:italic><jats:sup>L9\u2032S\/L9\u2032S<\/jats:sup>male mice exhibited impaired learning and memory. The deficit was rescued by low-dose nicotine exposure. Electrophysiological studies demonstrated that hypersensitive \u03b12 nAChRs potentiate acetylcholine-induced ion channel flux in oocytes and acute nicotine-induced facilitation of dorsal\/intermediate CA1 hippocampal long-term potentiation in<jats:italic>Chrna2<\/jats:italic><jats:sup>L9\u2032S\/L9\u2032S<\/jats:sup>mice. Adolescent male mice null for the \u03b12 nAChR subunit exhibited a baseline deficit in learning that was not reversed by an acute dose of nicotine. These effects were not influenced by locomotor, sensory or anxiety-related measures. Our results demonstrated that \u03b12* nAChRs influenced hippocampus-dependent learning and memory, as well as nicotine-facilitated CA1 hippocampal synaptic plasticity.<\/jats:p>","DOI":"10.1101\/lm.045369.117","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T00:40:22Z","timestamp":1494895222000},"page":"231-244","source":"Crossref","is-referenced-by-count":26,"title":["\u03b12* Nicotinic acetylcholine receptors influence hippocampus-dependent learning and memory in adolescent mice"],"prefix":"10.1101","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2425-1096","authenticated-orcid":false,"given":"Shahrdad","family":"Lotfipour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celina","family":"Mojica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakura","family":"Nakauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Lipovsek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Silverstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Cushman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Tirtorahardjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Poulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Bel\u00e9n","family":"Elgoyhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katumi","family":"Sumikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Fanselow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Boulter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2017,5,15]]},"reference":[{"key":"2021111207471925000_24.6.231.1","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1523\/JNEUROSCI.19-03-01106.1999","article-title":"Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination","volume":"19","year":"1999","journal-title":"J Neurosci"},{"key":"2021111207471925000_24.6.231.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193785"},{"key":"2021111207471925000_24.6.231.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.21.7763"},{"key":"2021111207471925000_24.6.231.4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0026-895X(25)10814-6","article-title":"Functional acetylcholine receptors expressed in Xenopus oocytes after injection of Torpedo \u03b2, \u03b3, and \u0394 subunit RNAs are a consequence of endogenous oocyte gene expression","volume":"37","year":"1990","journal-title":"Mol Pharmacol"},{"key":"2021111207471925000_24.6.231.5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.neuropharm.2015.09.022","article-title":"Early postnatal nicotine exposure disrupts the \u03b12* nicotinic acetylcholine receptor-mediated control of oriens-lacunosum moleculare cells during adolescence in rats","volume":"101","year":"2016","journal-title":"Neuropharmacology"},{"key":"2021111207471925000_24.6.231.6","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1111\/j.1530-0277.2011.01546.x","article-title":"Behavioral pharmacogenetic analysis on the role of the \u03b14 GABA(A) receptor subunit in the ethanol-mediated impairment of hippocampus-dependent contextual learning","volume":"35","year":"2011","journal-title":"Alcohol Clin Exp Res"},{"key":"2021111207471925000_24.6.231.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0624-8"},{"key":"2021111207471925000_24.6.231.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3242-07.2007"},{"key":"2021111207471925000_24.6.231.9","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90208-5"},{"key":"2021111207471925000_24.6.231.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.09.009"},{"key":"2021111207471925000_24.6.231.11","doi-asserted-by":"publisher","DOI":"10.3758\/BF03205285"},{"key":"2021111207471925000_24.6.231.12","doi-asserted-by":"publisher","DOI":"10.1037\/h0077609"},{"key":"2021111207471925000_24.6.231.13","unstructured":"Fox RR , Witham BA . 1997. 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