Nature communications · 2026
Purkinje cell intrinsic activity shapes cerebellar development and function.
СтатьяНазвание и аннотация: Перевод в очереди
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Osório Catarina, White Joshua J, Torrents-Solé Paula, Yang Jie, Mandemaker Nienke, Olivero Federico, Kirwan Freya, Post Laura, Hemmat Zahra, de Winter Fred, Regolo Eleonora, Fiocchi Francesca Romana, Serra Inês, Tjon Saffira, Ozgur Zeliha, van den Hout Mirjam C G N, van IJcken Wilfred F J, López-Bendito Guillermina, Badura Aleksandra, Lim Lynette, van Woerden Geeske M, Schonewille Martijn
Аннотация
The emergence of functional cerebellar circuits is heavily influenced by activity-dependent processes. However, the contribution of intrinsic Purkinje cell activity to cerebellar development remains less understood. Here, we demonstrate that before synaptic networks mature, Purkinje cell intrinsic activity is essential for regulating dendritic growth, establishing connections with cerebellar nuclei, and ensuring proper cerebellar function. Disrupting this activity during the postnatal period impairs motor function, with earlier perturbations causing more severe deficits. Importantly, only early developmental disruptions lead to pronounced defects in cellular morphology, highlighting key temporal windows for dendritic growth and maturation. Transcriptomic analyses reveal that early intrinsic activity drives the expression of activity-dependent genes, including Prkcg and Car8, which are essential for dendritic development. Our findings emphasize the importance of temporally regulated intrinsic activity in Purkinje cells in guiding cerebellar circuit development, providing a potential unifying mechanism underlying cerebellum-associated disorders.