{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:21:46Z","timestamp":1789370506095,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008582","name":"McGill University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008582","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Spinocerebellar ataxia type 6 (SCA6) is a midlife\u2010onset neurodegenerative disease caused by a <jats:italic>CACNA1A<\/jats:italic> mutation; <jats:italic>CACNA1A<\/jats:italic> is also implicated in cerebellar development.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We have previously shown that when disease symptoms are present in midlife in SCA6<jats:sup>84Q\/84Q<\/jats:sup> mice, cerebellar Purkinje cells spike with reduced rate and precision. In contrast, we find that during postnatal development (P10\u201313), SCA6<jats:sup>84Q\/84Q<\/jats:sup> Purkinje cells spike with elevated rate and precision.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Although surplus climbing fibres are linked to ataxia in other mouse models, we found surplus climbing fibre inputs on developing (P10\u201313) SCA6<jats:sup>84Q\/84Q<\/jats:sup> Purkinje cells when motor deficits were not detected.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Developmental alterations were transient and were no longer observed in weanling (P21\u201324) SCA6<jats:sup>84Q\/84Q<\/jats:sup> Purkinje cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results suggest that changes in the developing cerebellar circuit can occur without detectable motor abnormalities, and that changes in cerebellar development may not necessarily persist into adulthood.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Although some neurodegenerative diseases are caused by mutations in genes that are known to regulate neuronal development, surprisingly, patients may not present disease symptoms until adulthood. Spinocerebellar ataxia type 6 (SCA6) is one such midlife\u2010onset disorder in which the mutated gene, <jats:italic>CACNA1A<\/jats:italic>, is implicated in cerebellar development. We wondered whether changes were observed in the developing cerebellum in SCA6 prior to the detection of motor deficits. To address this question, we used a transgenic mouse with a hyper\u2010expanded triplet repeat (SCA6<jats:sup>84Q\/84Q<\/jats:sup>) that displays late\u2010onset motor deficits at 7 months, and measured cerebellar Purkinje cell synaptic and intrinsic properties during postnatal development. We found that firing rate and precision were enhanced during postnatal development in P10\u201313 SCA6<jats:sup>84Q\/84Q<\/jats:sup> Purkinje cells, and observed surplus multiple climbing fibre innervation without changes in inhibitory input or dendritic structure during development. Although excess multiple climbing fibre innervation has been associated with ataxic symptoms in several adult transgenic mice, we observed no detectable changes in cerebellar\u2010related motor behaviour in developing SCA6<jats:sup>84Q\/84Q<\/jats:sup> mice. Interestingly, we found that developmental alterations were transient, as both Purkinje cell firing properties and climbing fibre innervation from weanling\u2010aged (P21\u201324) SCA6<jats:sup>84Q\/84Q<\/jats:sup> mice were indistinguishable from litter\u2010matched control mice. Our results demonstrate that significant alterations in neuronal circuit development may be observed without any detectable behavioural read\u2010out, and that early changes in brain development may not necessarily persist into adulthood in midlife\u2010onset diseases.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp273184","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T09:46:45Z","timestamp":1471427205000},"page":"949-966","source":"Crossref","is-referenced-by-count":33,"title":["Transient cerebellar alterations during development prior to obvious motor phenotype in a mouse model of spinocerebellar ataxia type 6"],"prefix":"10.1113","volume":"595","author":[{"given":"Sriram","family":"Jayabal","sequence":"first","affiliation":[{"name":"Department of Biology McGill University  Montreal H3G 0B1 Canada"},{"name":"Integrated Program in Neuroscience McGill University  Montreal H3G 0B1 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