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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,2]]},"abstract":"<jats:p>\n                    Although a wide variety of genetic tools has been developed to study learning and memory, the molecular basis of memory encoding remains incompletely understood. Here, we undertook an unbiased approach to identify novel genes critical for memory encoding. From a large-scale, in\u00a0vivo mutagenesis screen using contextual fear conditioning, we isolated in mice a mutant, named\n                    <jats:italic>Clueless<\/jats:italic>\n                    , with spatial learning deficits. A causative missense mutation (G434V) was found in the voltage-gated potassium channel, subfamily C member 3 (\n                    <jats:italic>Kcnc3)<\/jats:italic>\n                    gene in a region that encodes a transmembrane voltage sensor. Generation of a Kcnc3\n                    <jats:sup>G434V<\/jats:sup>\n                    CRISPR mutant mouse confirmed this mutation as the cause of the learning defects. While G434V had no effect on transcription, translation, or trafficking of the channel, electrophysiological analysis of the G434V mutant channel revealed a complete loss of voltage-gated conductance, a broadening of the action potential, and decreased neuronal firing. Together, our findings have revealed a role for\n                    <jats:italic>Kcnc3<\/jats:italic>\n                    in learning and memory.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2204901119","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T14:37:08Z","timestamp":1658846228000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["A missense mutation in\n                    <i>Kcnc3<\/i>\n                    causes hippocampal learning deficits in mice"],"prefix":"10.1073","volume":"119","author":[{"given":"Pin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9089-7485","authenticated-orcid":false,"given":"Kazuhiro","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Northwestern University, Evanston, IL 60208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Gao","sequence":"additional","affiliation":[{"name":"Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9092-2230","authenticated-orcid":false,"given":"Eleanor H.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Columbia University, New York, NY 10032"},{"name":"Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guocun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chryshanthi M.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6643-7465","authenticated-orcid":false,"given":"Vivek","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Ping","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390"},{"name":"Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390"},{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9152"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S.","family":"Pawlowski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9152"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell D.","family":"Frye","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Kourrich","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390"},{"name":"Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7851-6902","authenticated-orcid":false,"given":"Eric R.","family":"Kandel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Columbia University, New York, NY 10032"},{"name":"Department of Neuroscience, Columbia University, New York, NY 10032"},{"name":"Kavli Institute of Brain Science, Columbia University, New York, NY 10032"},{"name":"Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032"},{"name":"HHMI, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-8878","authenticated-orcid":false,"given":"Joseph S.","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390"},{"name":"HHMI, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"a021741","DOI":"10.1101\/cshperspect.a021741","article-title":"The regulation of transcription in memory consolidation","volume":"7","author":"Alberini C. M.","year":"2014","unstructured":"C. M. Alberini, E. R. 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