Differential spatiotemporal development of Purkinje cell populations and cerebellum-dependent sensorimotor behaviors
- Erasmus Medical Center, Netherlands
- King's College London, United Kingdom
- Baylor College of Medicine, United States
Abstract
Distinct populations of Purkinje cells (PCs) with unique molecular and connectivity features are at the core of the modular organization of the cerebellum. Previously, we showed that firing activity of Purkinje cells differs between ZebrinII-positive (Z+) and -negative (Z−) cerebellar modules (Zhou et al., 2014; Wu et al., 2019). Here, we investigate the timing and extent of PC differentiation during development in mice. We found that several features of PCs, including activity levels, dendritic arborisation, axonal shape and climbing fiber input, develop differentially between nodular and anterior PC populations. Although all PCs show a particularly rapid development in the second postnatal week, anterior PCs typically have a prolonged physiological and dendritic maturation. In line herewith, younger mice exhibit attenuated anterior-dependent eyeblink conditioning, but faster nodular-dependent compensatory eye movement adaptation. Our results indicate that specific cerebellar regions have unique developmental timelines which match with their related, specific forms of cerebellum-dependent behaviors.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Gerrit Cornelis Beekhof
Ingo HMS Nettersheim
Martijn Schonewille
Funding
H2020 European Research Council (ERC-Stg #680235)
- Martijn Schonewille
ZonMw (ZonMW-451001027)
- Catarina Osório
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (#016.121.346)
- Freek E Hoebeek
ZonMw (#91210067)
- Freek E Hoebeek
C.J. Vaillant Fund
- Freek E Hoebeek
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (016.Veni.192.270)
- Joshua J White
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed under a project license approved by the Dutch Central Committee for Animal Experiments (CCD, AVD #101002015273). Each experiment was separately verified and approved by the Animal Welfare Body (IvD/AWB, various work protocols). All surgeries were performed under isoflurane anesthesia combined with local anesthetics and analgesics in an effort to minimize suffering.
Copyright
© 2021, Beekhof et al.
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.
Metrics
-
- 3,701
- views
-
- 496
- downloads
-
- 21
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Differential spatiotemporal development of Purkinje cell populations and cerebellum-dependent sensorimotor behaviors
eLife 10:e63668.
https://doi.org/10.7554/eLife.63668
Further reading
-
- Developmental Biology
- Genetics and Genomics
New developmental programs can evolve through adaptive changes to gene expression. The annelid Streblospio benedicti has a developmental dimorphism, which provides a unique intraspecific framework for understanding the earliest genetic changes that take place during developmental divergence. Using comparative RNAseq through ontogeny, we find that only a small proportion of genes are differentially expressed at any time, despite major differences in larval development and life history. These genes shift expression profiles across morphs by either turning off any expression in one morph or changing the timing or amount of gene expression. We directly connect the contributions of these mechanisms to differences in developmental processes. We examine F1 offspring – using reciprocal crosses – to determine maternal mRNA inheritance and the regulatory architecture of gene expression. These results highlight the importance of both novel gene expression and heterochronic shifts in developmental evolution, as well as the trans-acting regulatory factors in initiating divergence.
-
- Cell Biology
- Developmental Biology
The formation of large endolysosomal structures in unfertilized eggs ensures that lysosomes remain dormant before fertilization, and then shift into clean-up mode after the egg-to-embryo transition.
