{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:45:31Z","timestamp":1792896331263,"version":"4.5.0"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>\n                    Studies in rodent models have revealed that oligomeric beta-amyloid protein [A\u03b2 (1\u201342)] plays an important role in the pathogenesis of Alzheimer\u2019s disease. Early elevations in hippocampal neuronal excitability caused by A\u03b2 (1\u201342) have been proposed to be mediated via enhanced activation of GluN2B-containing N-methyl-D-aspartate receptors (NMDAR). To what extent GluN2A or GluN2B-containing NMDAR contribute to A\u03b2 (1\u201342)-mediated impairments of hippocampal function in advanced rodent age is unclear. Here, we assessed hippocampal long-term potentiation (LTP) and neuronal responses 4\u20135\u2009weeks after bilateral intracerebral inoculation of 8\u201315\u2009month old GluN2A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    or GluN2B\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    transgenic mice with oligomeric A\u03b2 (1\u201342), or control peptide. Whole-cell patch-clamp recordings in CA1 pyramidal neurons revealed a more positive resting membrane potential and increased total spike time in GluN2A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    , but not GluN2B\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    -hippocampi following treatment with A\u03b2 (1\u201342) compared to controls. Action potential 20%-width was increased, and the descending slope was reduced, in A\u03b2\u2013treated GluN2A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    , but not GluN2B\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    hippocampi. Sag ratio was increased in A\u03b2\u2013treated GluN2B\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    -mice. Firing frequency was unchanged in wt, GluN2A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    , and GluN2B\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    hippocampi after A\u03b2\u2013treatment. Effects were not significantly different from responses detected under the same conditions in wt littermates, however. LTP that lasted for over 2\u2009h in wt hippocampal slices was significantly reduced in GluN2A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    and was impaired for 15\u2009min in GluN2B\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    -hippocampi compared to wt littermates. Furthermore, LTP (&amp;gt;2\u2009h) was significantly impaired in A\u03b2\u2013treated hippocampi of wt littermates compared to wt treated with control peptide. LTP induced in A\u03b2\u2013treated GluN2A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    and GluN2B\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    -hippocampi was equivalent to LTP in control peptide-treated transgenic and A\u03b2\u2013treated wt animals. Taken together, our data indicate that knockdown of GluN2A subunits subtly alters membrane properties of hippocampal neurons and reduces the magnitude of LTP. GluN2B knockdown reduces the early phase of LTP but leaves later phases intact. A\u03b2 (1\u201342)-treatment slightly exacerbates changes in action potential properties in GluN2A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    -mice. However, the vulnerability of the aging hippocampus to A\u03b2\u2013mediated impairments of LTP is not mediated by GluN2A or GluN2B-containing NMDAR.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2024.1377085","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:32:11Z","timestamp":1716165131000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["GluN2A or GluN2B subunits of the NMDA receptor contribute to changes in neuronal excitability and impairments in LTP in the hippocampus of aging mice but do not mediate detrimental effects of oligomeric A\u03b2 (1\u201342)"],"prefix":"10.3389","volume":"16","author":[{"given":"Nicolina","family":"S\u00fcdkamp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena","family":"Shchyglo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Manahan-Vaughan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.neurobiolaging.2007.01.003","article-title":"Abeta(1\u201342) modulation of Akt phosphorylation via alpha7 nAChR and NMDA receptors","volume":"29","author":"Abbott","year":"2008","journal-title":"Neurobiol. 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