Purkinje cell intrinsic activity shapes cerebellar development and function
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.
Authors
- Zeliha Özgür (ORCID: https://orcid.org/0000-0002-7171-1884)
- Aleksandra Badura (ORCID: https://orcid.org/0000-0002-0119-5108)
- Laura Post
- Federico Olivero (ORCID: https://orcid.org/0000-0002-1998-3153)
- Fred de Winter (ORCID: https://orcid.org/0000-0002-3042-2429)
- Martijn Schonewille (ORCID: https://orcid.org/0000-0002-2675-1393)
- Francesca Romana Fiocchi
- Joshua J. White (ORCID: https://orcid.org/0000-0002-6218-623X)
- Lynette Lim (ORCID: https://orcid.org/0000-0003-4179-8373)
- Wilfred F. J. van IJcken (ORCID: https://orcid.org/0000-0002-0421-8301)
- Eleonora Regolo
- Saffira Tjon
- Freya Kirwan
- Nienke Mandemaker
- Mirjam CGN van den Hout
- Paula Torrents-Solé (ORCID: https://orcid.org/0009-0008-1321-9956)
- Guillermina López-Bendito
- Inês Serra
- Catarina Osório
- Geeske M. van Woerden
- Zahra Hemmat
- Jie Yang
Institutions
- Netherlands Institute for Neuroscience (NL)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Consejo Superior de Investigaciones Científicas (ES)
- Erasmus MC (NL)
- Instituto de Neurociencias (ES)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- Erasmus University Rotterdam (NL)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-03-09
- DOI
- https://doi.org/10.1038/s41467-026-70355-w
- Primary Topic
- Vestibular and auditory disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00