Purkinje cell intrinsic activity shapes cerebellar development and function

Catarina Osório; Joshua J White; Paula Torrents-Solé; Jie Yang; Nienke Mandemaker; Federico Olivero; Freya Kirwan; Laura Post; Zahra Hemmat; Fred de Winter; Eleonora Regolo; Francesca Romana Fiocchi; Inês Serra; Saffira Tjon; Zeliha Ozgur; Mirjam C G N van den Hout; Wilfred F J van IJcken; Guillermina López-Bendito; Aleksandra Badura; Lynette Lim; Geeske M van Woerden; Martijn Schonewille

doi:10.1038/s41467-026-70355-w

Purkinje cell intrinsic activity shapes cerebellar development and function

Catarina Osório
, Joshua J White
, Paula Torrents-Solé
, Jie Yang
, Nienke Mandemaker
, Federico Olivero
, Freya Kirwan
, Laura Post
, Zahra Hemmat
, Fred de Winter
, Eleonora Regolo
, Francesca Romana Fiocchi
, Inês Serra
, Saffira Tjon
, Zeliha Ozgur
, Mirjam C G N van den Hout
, Wilfred F J van IJcken
, Guillermina López-Bendito
, Aleksandra Badura
, Lynette Lim

Geeske M van Woerden, Martijn Schonewille

Netherlands Institute for Neuroscience (NIN)

Laboratory for Regeneration of Sensorimotor Systems, Netherlands Institute for Neuroscience Amsterdam, Netherlands.

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

1790 Downloads (Pure)

Abstract

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.

Original language	English
Article number	3688
Journal	Nature Communications
Volume	17
DOIs	https://doi.org/10.1038/s41467-026-70355-w
Publication status	Published - 09 Mar 2026

Access to Document

10.1038/s41467-026-70355-w

Osorio2026Final published version, 22.8 MB

Cite this

Osório, C., White, J. J., Torrents-Solé, P., Yang, J., Mandemaker, N., Olivero, F., Kirwan, F., Post, L., Hemmat, Z., de Winter, F., Regolo, E., Fiocchi, F. R., Serra, I., Tjon, S., Ozgur, Z., van den Hout, M. C. G. N., van IJcken, W. F. J., López-Bendito, G., Badura, A., ... Schonewille, M. (2026). Purkinje cell intrinsic activity shapes cerebellar development and function. Nature Communications, 17, Article 3688. https://doi.org/10.1038/s41467-026-70355-w

@article{78d4e0922b3e42e597bc25a8af87a762,

title = "Purkinje cell intrinsic activity shapes cerebellar development and function",

abstract = "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.",

author = "Catarina Os{\'o}rio and White, \{Joshua J\} and Paula Torrents-Sol{\'e} and Jie Yang and Nienke Mandemaker and Federico Olivero and Freya Kirwan and Laura Post and Zahra Hemmat and \{de Winter\}, Fred and Eleonora Regolo and Fiocchi, \{Francesca Romana\} and In{\^e}s Serra and Saffira Tjon and Zeliha Ozgur and \{van den Hout\}, \{Mirjam C G N\} and \{van IJcken\}, \{Wilfred F J\} and Guillermina L{\'o}pez-Bendito and Aleksandra Badura and Lynette Lim and \{van Woerden\}, \{Geeske M\} and Martijn Schonewille",

note = "{\textcopyright} 2026. The Author(s).",

year = "2026",

month = mar,

day = "9",

doi = "10.1038/s41467-026-70355-w",

language = "English",

volume = "17",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Osório, C, White, JJ, Torrents-Solé, P, Yang, J, Mandemaker, N, Olivero, F, Kirwan, F, Post, L, Hemmat, Z, de Winter, F, Regolo, E, Fiocchi, FR, Serra, I, Tjon, S, Ozgur, Z, van den Hout, MCGN, van IJcken, WFJ, López-Bendito, G, Badura, A, Lim, L, van Woerden, GM & Schonewille, M 2026, 'Purkinje cell intrinsic activity shapes cerebellar development and function', Nature Communications, vol. 17, 3688. https://doi.org/10.1038/s41467-026-70355-w

TY - JOUR

T1 - Purkinje cell intrinsic activity shapes cerebellar development and function

AU - Osório, Catarina

AU - White, Joshua J

AU - Torrents-Solé, Paula

AU - Yang, Jie

AU - Mandemaker, Nienke

AU - Olivero, Federico

AU - Kirwan, Freya

AU - Post, Laura

AU - Hemmat, Zahra

AU - de Winter, Fred

AU - Regolo, Eleonora

AU - Fiocchi, Francesca Romana

AU - Serra, Inês

AU - Tjon, Saffira

AU - Ozgur, Zeliha

AU - van den Hout, Mirjam C G N

AU - van IJcken, Wilfred F J

AU - López-Bendito, Guillermina

AU - Badura, Aleksandra

AU - Lim, Lynette

AU - van Woerden, Geeske M

AU - Schonewille, Martijn

PY - 2026/3/9

Y1 - 2026/3/9

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-026-70355-w

DO - 10.1038/s41467-026-70355-w

M3 - Article

C2 - 41803111

SN - 2041-1723

VL - 17

JO - Nature Communications

JF - Nature Communications

M1 - 3688

ER -

Purkinje cell intrinsic activity shapes cerebellar development and function

Abstract

Access to Document

Fingerprint

Cite this