Lifelong regeneration of cerebellar Purkinje cells after induced cell ablation in zebrafish

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Abstract

Zebrafish have an impressive capacity to regenerate neurons in the central nervous system. However, regeneration of the principal neuron of the evolutionary conserved cerebellum, the Purkinje cell (PC), is believed to be limited to developmental stages based on invasive lesions. In contrast, non-invasive cell type specific ablation by induced apoptosis closely represents a process of neurodegeneration. We demonstrate that the ablated larval PC population entirely recovers in number, quickly reestablishes electrophysiological properties, and properly integrates into circuits to regulate cerebellum-controlled behavior. PC progenitors are present in larvae and adults, and PC ablation in adult cerebelli results in an impressive PC regeneration of different PC subtypes able to restore behavioral impairments. Interestingly, caudal PCs are more resistant to ablation and regenerate more efficiently, suggesting a rostro-caudal pattern of de- and regeneration properties. These findings demonstrate that the zebrafish cerebellum is able to regenerate functional PCs during all stages of the animal's life.

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Detailed numbers for statistics shown in the figures are provided in Supplementary Table 1. All data generated or analyzed during this study are included in the manuscript and supporting files.Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact.

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Sol Pose-Méndez

Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany

For correspondence
s.pose-mendez@tu-braunschweig.de

Competing interests
The authors declare that no competing interests exist.
Paul Schramm

Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0894-2348
Barbara Winter

Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany

Competing interests
The authors declare that no competing interests exist.
Jochen C Meier

Cell Physiology, Technische Universität Braunschweig, Braunschweig, Germany

Competing interests
The authors declare that no competing interests exist.
Konstantinos Ampatzis

Neuroscience Department, Karolinska Institute, Stockholm, Sweden

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7998-6463
Reinhard W Köster

Cellular and Molecular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany

For correspondence
r.koester@tu-bs.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6593-8196

Funding

Horizon 2020 Framework Programme (H2020-MSCA-IF-2015,No 703961)

Sol Pose-Méndez

Volkswagen Foundation (HOMEO-HIRN,ZN3673)

Jochen C Meier
Reinhard W Köster

Bundesministerium für Bildung und Forschung (Era-Net NEURON II CIPRESS)

Jochen C Meier

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental protocols for animal research were approved by governmental authorities of Lower Saxony, LAVES, (AZ33.19-42502-04-20/3593). All efforts were made to use only the minimum number of experimental animals necessary to obtain reliable scientific data.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.