A quantitative framework for whole-body coordination reveals specific deficits in freely walking ataxic mice

Abstract

The coordination of movement across the body is a fundamental, yet poorly understood aspect of motor control. Mutant mice with cerebellar circuit defects exhibit characteristic impairments in locomotor coordination; however, the fundamental features of this gait ataxia have not been effectively isolated. Here we describe a novel system (LocoMouse) for analyzing limb, head, and tail kinematics of freely walking mice. Analysis of visibly ataxic Purkinje cell degeneration (pcd) mice reveals that while differences in the forward motion of individual paws are fully accounted for by changes in walking speed and body size, more complex 3D trajectories and, especially, inter-limb and whole-body coordination are specifically impaired. Moreover, the coordination deficits in pcd are consistent with a failure to predict and compensate for the consequences of movement across the body. These results isolate specific impairments in whole-body coordination in mice and provide a quantitative framework for understanding cerebellar contributions to coordinated locomotion.

Article and author information

Author details

  1. Ana S Machado

    Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  2. Dana M Darmohray

    Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  3. Joao Fayad

    Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  4. Hugo G Marques

    Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  5. Megan R Carey

    Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal
    For correspondence
    megan.carey@neuro.fchampalimaud.org
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Indira M Raman, Northwestern University, United States

Ethics

Animal experimentation: All procedures were reviewed and performed in accordance with the Champalimaud Centre for the Unknown Ethics Committee guidelines, and approved by the Portuguese Direcção Geral de Veterinária (Ref. No. 0421/000/000/2015).

Version history

  1. Received: April 2, 2015
  2. Accepted: October 2, 2015
  3. Accepted Manuscript published: October 3, 2015 (version 1)
  4. Version of Record published: November 10, 2015 (version 2)

Copyright

© 2015, Machado 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

  • 9,579
    views
  • 1,449
    downloads
  • 139
    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)

  1. Ana S Machado
  2. Dana M Darmohray
  3. Joao Fayad
  4. Hugo G Marques
  5. Megan R Carey
(2015)
A quantitative framework for whole-body coordination reveals specific deficits in freely walking ataxic mice
eLife 4:e07892.
https://doi.org/10.7554/eLife.07892

Share this article

https://doi.org/10.7554/eLife.07892

Further reading

    1. Cell Biology
    2. Neuroscience
    Marcos Moreno-Aguilera, Alba M Neher ... Carme Gallego
    Research Article Updated

    Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here, we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.

    1. Genetics and Genomics
    2. Neuroscience
    Kenneth Chiou, Noah Snyder-Mackler
    Insight

    Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.