{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:29:55Z","timestamp":1778837395169,"version":"3.51.4"},"posted":{"date-parts":[[2023,11,2]]},"group-title":"Neuroscience","reference-count":76,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cerebellar damage early in life often causes long-lasting motor, social, and cognitive impairments, suggesting the roles of the cerebellum in developing a broad spectrum of behaviors. This recent finding has promoted research on how cerebellar damage affects the development of the cerebral cortex, the brain region responsible for higher-order control of all behaviors. However, the cerebral cortex is not directly connected to the cerebellum. The thalamus is the direct postsynaptic target of the cerebellum, sending cerebellar outputs to the cerebral cortex. Despite its crucial position in cerebello-cerebral interaction, thalamic susceptibility to cerebellar damage remains largely unclear. Here, we studied the consequences of early cerebellar perturbation on thalamic development. Whole-cell patch-clamp recordings showed that the synaptic organization of the cerebellothlamic circuit is similar to that of the primary sensory thalamus, in which aberrant sensory activity alters synaptic circuit formation. The hemizygous deletion of the tuberous sclerosis complex-1 (\n                  <jats:italic>Tsc1<\/jats:italic>\n                  ) gene in the Purkinje cell\u2014known to cause Purkinje cell hypoactivity and autistic behaviors\u2014did not alter cerebellothalamic synapses or intrinsic membrane properties of thalamic neurons. However, the ablation of Purkinje cells in the developing cerebellum strengthened the cerebellothalamic synapses and enhanced thalamic suprathreshold activities. These results suggest that the cerebellothalamic circuit is resistant to moderate perturbation in the developing cerebellum, such as the reduced firing rate of Purkinje cells, and that autistic behaviors are not necessarily linked to thalamic abnormality. Still, Purkinje cell loss alters the thalamic circuit, suggesting the vulnerability of the thalamus to substantial disturbance in the developing cerebellum.\n                <\/jats:p>","DOI":"10.1101\/2023.11.01.564864","type":"posted-content","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T06:35:16Z","timestamp":1698906916000},"source":"Crossref","is-referenced-by-count":2,"title":["Loss of Purkinje cells in the developing cerebellum strengthens the cerebellothalamic synapses"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5034-5777","authenticated-orcid":false,"given":"Hiroshi","family":"Nishiyama","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2463-4887","authenticated-orcid":false,"given":"Boris V.","family":"Zemelman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023110617551644000_2023.11.01.564864v1.1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.106542"},{"key":"2023110617551644000_2023.11.01.564864v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01162-9"},{"key":"2023110617551644000_2023.11.01.564864v1.3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36401"},{"key":"2023110617551644000_2023.11.01.564864v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/121.5.889"},{"key":"2023110617551644000_2023.11.01.564864v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<93::AID-GENE10>3.0.CO;2-W"},{"key":"2023110617551644000_2023.11.01.564864v1.6","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1969.32.6.1044"},{"key":"2023110617551644000_2023.11.01.564864v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fncom.2013.00163"},{"key":"2023110617551644000_2023.11.01.564864v1.8","doi-asserted-by":"crossref","unstructured":"Calin-Jageman RJ & Cumming G (2019). 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