{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:44:45Z","timestamp":1792129485832,"version":"4.4.0"},"reference-count":38,"publisher":"Society for Neuroscience","issue":"6","license":[{"start":{"date-parts":[[2008,8,6]],"date-time":"2008-08-06T00:00:00Z","timestamp":1217980800000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2008,2,6]]},"abstract":"<jats:p>The \u03b42 glutamate receptor (GluR\u03b42) is predominantly expressed in Purkinje cells and plays crucial roles in cerebellar functions:<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice display ataxia and impaired motor learning. In addition, long-term depression (LTD) at parallel fiber (PF)\u2013Purkinje cell synapses is abrogated, and synapse formation with PFs and climbing fibers (CFs) is severely disturbed in<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>Purkinje cells. Recently, we demonstrated that abrogated LTD was restored in<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>Purkinje cells by the virus-mediated expression of the wild-type<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic>transgene (<jats:italic>Tg<\/jats:italic><jats:sub>wt<\/jats:sub>) but not by that of mutant<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic>lacking the C-terminal seven residues to which several PDZ proteins bind (<jats:italic>Tg<\/jats:italic><jats:sub>\u0394CT7<\/jats:sub>). These results indicated that the C terminus of GluR\u03b42 conveys the signal(s) necessary for LTD. In contrast, other phenotypes of<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>cerebellum, especially morphological abnormalities at PF and CF synapses, could not be rescued by virus-mediated transient expression. Thus, whether these phenotypes are mediated by the same signaling pathway remains unclear. To address these issues and to further delineate the function of GluR\u03b42<jats:italic>in vivo<\/jats:italic>, we generated transgenic mice that expressed<jats:italic>Tg<\/jats:italic><jats:sub>\u0394CT7<\/jats:sub>on a<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>background. Interestingly, although<jats:italic>Tg<\/jats:italic><jats:sub>\u0394CT7<\/jats:sub>restored abnormal PF and CF synapse formation almost completely, it could not rescue abrogated LTD in<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>Purkinje cells. Furthermore, although the gross motor discoordination of<jats:italic>GluR<\/jats:italic>\u03b4<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice was restored, the cerebellar motor learning underlying delayed eyeblink conditioning remained impaired. These results indicate that LTD induction and motor learning are regulated by signaling via the C-terminal end of GluR\u03b42, whereas other functions may be differentially regulated by other regions of GluR\u03b42.<\/jats:p>","DOI":"10.1523\/jneurosci.2553-07.2008","type":"journal-article","created":{"date-parts":[[2008,2,6]],"date-time":"2008-02-06T17:27:56Z","timestamp":1202318876000},"page":"1460-1468","source":"Crossref","is-referenced-by-count":82,"title":["Differential Regulation of Synaptic Plasticity and Cerebellar Motor Learning by the C-Terminal PDZ-Binding Motif of 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