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The most common models, carrying extra-copies of overlapping fragments of mouse chromosome 16 that is syntenic to human chromosome 21, are Ts2Cje, Ts1Cje and Ts1Rhr mice. In electrophysiological analyses using hippocampal slices, we found that the later phase of the depolarization during tetanic stimulation, which was regulated by GABA<jats:sub>B<\/jats:sub> receptors, was significantly smaller in Ts1Cje and Ts2Cje mice than that in WT controls but not in Ts1Rhr mice. Furthermore, isolated GABA<jats:sub>B<\/jats:sub> receptor-mediated inhibitory synaptic responses were larger in Ts1Cje mice. To our knowledge, this is the first report that directly shows the enhancement of GABA<jats:sub>B<\/jats:sub> receptor-mediated synaptic currents in Ts1Cje mice. These results suggest that GABA<jats:sub>B<\/jats:sub> receptor-mediated synaptic inhibition was enhanced in Ts1Cje and Ts2Cje mice but not in Ts1Rhr mice. The <jats:italic>Cbr1<\/jats:italic> gene, which is present in three copies in Ts1Cje and Ts2Cje but not in Ts1Rhr, encodes carbonyl reductase that may facilitate GABA<jats:sub>B<\/jats:sub>-receptor activity through a reduction of prostaglandin E2 (PGE2). Interestingly, we found that a reduction of PGE2 and an memory impairment in Ts1Cje mice were alleviated when only <jats:italic>Cbr1<\/jats:italic> was set back to two copies (Ts1Cje;<jats:italic>Cbr1<\/jats:italic><jats:sup>+\/+\/\u2212<\/jats:sup>). However, the GABA<jats:sub>B<\/jats:sub> receptor-dependent enhancement of synaptic inhibition in Ts1Cje was unaltered in Ts1Cje;<jats:italic>Cbr1<\/jats:italic><jats:sup>+\/+\/\u2212<\/jats:sup> mice. These results indicate that <jats:italic>Cbr1<\/jats:italic> is one of the genes responsible for DS cognitive impairments and the gene(s) other than <jats:italic>Cbr1<\/jats:italic>, which is included in Ts1Cje but not in Ts1Rhr, is responsible for the GABA<jats:sub>B<\/jats:sub> receptor-dependent over-inhibition.<\/jats:p>","DOI":"10.1038\/s41598-020-71085-9","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T10:04:04Z","timestamp":1598349844000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Impairment of spatial memory accuracy improved by Cbr1 copy number resumption and GABAB receptor-dependent enhancement of synaptic inhibition in Down syndrome model mice"],"prefix":"10.1038","volume":"10","author":[{"given":"Fumiko","family":"Arima-Yoshida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Raveau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Shimohata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Amano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Watanave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuka","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Usui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Sago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuko","family":"Mataga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Miyakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Yamakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Manabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,25]]},"reference":[{"key":"71085_CR1","first-page":"1223","volume-title":"The metabolic and molecular bases inherited disease","author":"CJ Epstein","year":"2001","unstructured":"Epstein, C. 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