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In this study, reversible open\u2010channel blockers of <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>s, memantine and phencyclidine (<jats:styled-content style=\"fixed-case\">PCP<\/jats:styled-content>) were used as tools to examine tonic <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>\u2010mediated signalling in rat hippocampal slices. Memantine in concentrations up to 10\u00a0\u03bc<jats:sc>m<\/jats:sc> had no effect on synaptically evoked <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>\u2010mediated responses in pyramidal neurons or <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>ergic interneurons. On the other hand, 10\u00a0\u03bc<jats:sc>m<\/jats:sc> memantine reduced tonic <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>\u2010mediated currents in <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>ergic interneurons by approximately 50%. These tonic <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>\u2010mediated currents in interneurons contributed significantly to the excitability of the interneurons as 10\u00a0\u03bc<jats:sc>m<\/jats:sc> memantine reduced the disynaptic inhibitory postsynaptic current in pyramidal cells by about 50%. Moreover, 10\u00a0\u03bc<jats:sc>m<\/jats:sc> memantine, but also <jats:styled-content style=\"fixed-case\">PCP<\/jats:styled-content> in concentrations \u2264\u00a01\u00a0\u03bc<jats:sc>m<\/jats:sc>, increased the magnitude of the population spike, likely because of disinhibition. The relatively higher impact of tonic <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>\u2010mediated signalling in interneurons was at least partly explained by the expression of GluN2D\u2010containing <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>s, which was not observed in mature pyramidal cells. The current results are consistent with the idea that low doses of readily reversible <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content> open\u2010channel blockers preferentially inhibit tonically active extrasynaptic <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>s, and they suggest that tonically active <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>s contribute more prominently to the intrinsic excitation in <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>ergic interneurons than in pyramidal cells. It is proposed that this specific difference between interneurons and pyramidal cells can explain the disinhibition caused by the Alzheimer's disease medication memantine.<\/jats:p>","DOI":"10.1111\/ejn.13128","type":"journal-article","created":{"date-parts":[[2015,11,8]],"date-time":"2015-11-08T19:41:14Z","timestamp":1447011674000},"page":"169-178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Tonically active <scp>NMDA<\/scp> receptors \u2013 a signalling mechanism critical for interneuronal excitability in the <scp>CA<\/scp>1 stratum radiatum"],"prefix":"10.1111","volume":"43","author":[{"given":"Ilse","family":"Riebe","sequence":"first","affiliation":[{"name":"Department of Physiology Institute of Neuroscience and Physiology The Sahlgrenska Academy Gothenburg University Medicinaregatan 11 405 30 Gothenburg 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