{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:33:37Z","timestamp":1792650817981,"version":"4.5.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["18H03379"],"award-info":[{"award-number":["18H03379"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["20K06906"],"award-info":[{"award-number":["20K06906"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20dm0207057"],"award-info":[{"award-number":["JP20dm0207057"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21dm0207111"],"award-info":[{"award-number":["JP21dm0207111"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,11,8]]},"abstract":"<jats:p>\n                    Thyroid hormones (THs) regulate gene expression by binding to nuclear TH receptors (TRs) in the cell. THs are indispensable for brain development. However, we have little knowledge about how congenital hypothyroidism in neurons affects functions of the central nervous system in adulthood. Here, we report specific TH effects on functional development of the cerebellum by using transgenic mice overexpressing a dominant-negative TR (Mf-1) specifically in cerebellar Purkinje cells (PCs). Adult Mf-1 mice displayed impairments in motor coordination and motor learning. Surprisingly, long-term depression (LTD)\u2013inductive stimulation caused long-term potentiation (LTP) at parallel fiber (PF)\u2013PC synapses in adult Mf-1 mice, although there was no abnormality in morphology or basal properties of PF\u2013PC synapses. The LTP phenotype was turned to LTD in Mf-1 mice when the inductive stimulation was applied in an extracellular high-Ca\n                    <jats:sup>2+<\/jats:sup>\n                    condition. Confocal calcium imaging revealed that dendritic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    elevation evoked by LTD-inductive stimulation is significantly reduced in Mf-1 PCs but not by PC depolarization only. Single PC messenger RNA quantitative analysis showed reduced expression of SERCA2 and IP\n                    <jats:sub>3<\/jats:sub>\n                    receptor type 1 in Mf-1 PCs, which are essential for mGluR1-mediated internal calcium release from endoplasmic reticulum in cerebellar PCs. These abnormal changes were not observed in adult-onset PC-specific TH deficiency mice created by adeno-associated virus vectors. Thus, we propose the importance of TH action during neural development in establishing proper cerebellar function in adulthood, independent of its morphology. The present study gives insight into the cellular and molecular mechanisms underlying congenital hypothyroidism\u2013induced dysfunctions of central nervous system and cerebellum.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2210645119","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T14:50:06Z","timestamp":1667400606000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Long-term depression\u2013inductive stimulation causes long-term potentiation in mouse Purkinje cells with a mutant thyroid hormone receptor"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5540-1459","authenticated-orcid":false,"given":"Ayane","family":"Ninomiya","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izuki","family":"Amano","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1841-3028","authenticated-orcid":false,"given":"Michifumi","family":"Kokubo","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-3402","authenticated-orcid":false,"given":"Yusuke","family":"Takatsuru","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health Sciences, Toyo University, Itakura 374-0193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumiyasu","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0721-4293","authenticated-orcid":false,"given":"Hirokazu","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7889-2542","authenticated-orcid":false,"given":"Nobutake","family":"Hosoi","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2247-9740","authenticated-orcid":false,"given":"Noriyuki","family":"Koibuchi","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.3.1097"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(00)00238-1"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-17"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12135"},{"key":"e_1_3_4_5_2","first-page":"1874","article-title":"\u03b2 1 isoform-specific regulation of a triiodothyronine-induced gene during cerebellar development","volume":"6","author":"Strait K. 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