{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:18:43Z","timestamp":1792804723879,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["GM118801"],"award-info":[{"award-number":["GM118801"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U54HD090256"],"award-info":[{"award-number":["U54HD090256"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Anesthesiology at the University of Wisconsin\u2013Madison","award":["GM118801"],"award-info":[{"award-number":["GM118801"]}],"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Department of Anesthesiology at the University of Wisconsin\u2013Madison","award":["U54HD090256"],"award-info":[{"award-number":["U54HD090256"]}],"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Point mutations in the \u03b22 (N265S) and \u03b23 (N265M) subunits of \u03b3-amino butyric acid type A receptors (GABAARs) that render them insensitive to the general anesthetics etomidate and propofol have been used to link modulation of \u03b22-GABAARs to sedation and \u03b23-GABAARs to surgical immobility. These mutations also alter GABA sensitivity, and mice carrying the \u03b23-N265M mutation have been reported to have impaired baseline memory. Here, we tested the effects of the \u03b22-N265M and \u03b23-N265M mutations on memory, movement, hotplate sensitivity, anxiety, etomidate-induced sedation, and intrinsic kinetics. We found that both \u03b22-N265M and \u03b23-N265M mice exhibited baseline deficits in the Context Preexposure Facilitation Effect learning paradigm. Exploratory activity was slightly greater in \u03b22-N265M mice, but there were no changes in either genotype in anxiety or hotplate sensitivity. \u03b22-N265M mice were highly resistant to etomidate-induced sedation, and heterozygous mice were partially resistant. In rapid solution exchange experiments, both mutations accelerated deactivation two- to three-fold compared to wild type receptors and prevented modulation by etomidate. This degree of change in the receptor deactivation rate is comparable to that produced by an amnestic dose of etomidate but in the opposite direction, indicating that intrinsic characteristics of GABAARs are optimally tuned under baseline conditions to support mnemonic function.<\/jats:p>","DOI":"10.3390\/ijms24065637","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T03:50:45Z","timestamp":1678938645000},"page":"5637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Changes in Memory, Sedation, and Receptor Kinetics Imparted by the \u03b22-N265M and \u03b23-N265M GABAA Receptor Point Mutations"],"prefix":"10.3390","volume":"24","author":[{"given":"Alifayaz","family":"Abdulzahir","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Lor","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Frelka","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1516-6260","authenticated-orcid":false,"given":"Robert A.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tips.2019.05.001","article-title":"Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery","volume":"40","author":"Hemmings","year":"2019","journal-title":"Trends Pharmacol. 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