Synaptic representation of locomotion in single cerebellar granule cells

  1. Kate Powell
  2. Alexandre Mathy
  3. Ian Duguid
  4. Michael Häusser  Is a corresponding author
  1. University College London, United Kingdom

Abstract

The cerebellum plays a crucial role in the regulation of locomotion, but how movement is represented at the synaptic level is not known. Here, we use in vivo patch-clamp recordings to show that locomotion can be directly read out from mossy fiber synaptic input and spike output in single granule cells. The increase in granule cell spiking during locomotion is enhanced by glutamate spillover currents recruited during movement. Surprisingly, the entire step sequence can be predicted from input EPSCs and output spikes of a single granule cell, suggesting that a robust gait code is present already at the cerebellar input layer and transmitted via the granule cell pathway to downstream Purkinje cells. Thus, synaptic input delivers remarkably rich information to single neurons during locomotion.

Article and author information

Author details

  1. Kate Powell

    Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  2. Alexandre Mathy

    Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  3. Ian Duguid

    Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Michael Häusser

    Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    For correspondence
    m.hausser@ucl.ac.uk
    Competing interests
    Michael Häusser, Reviewing editor, eLife.

Reviewing Editor

  1. Indira M Raman, Northwestern University, United States

Ethics

Animal experimentation: This study was performed in strict accordance with UK Home Office regulations. Experiments were carried out under Project Licence 70/7833 issued by the Home Office, which was issued following local ethical review, and under the relevant Personal Licences issued by the Home Office. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Version history

  1. Received: March 3, 2015
  2. Accepted: June 16, 2015
  3. Accepted Manuscript published: June 17, 2015 (version 1)
  4. Version of Record published: July 13, 2015 (version 2)

Copyright

© 2015, Powell 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

  • 4,295
    Page views
  • 1,191
    Downloads
  • 78
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

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. Kate Powell
  2. Alexandre Mathy
  3. Ian Duguid
  4. Michael Häusser
(2015)
Synaptic representation of locomotion in single cerebellar granule cells
eLife 4:e07290.
https://doi.org/10.7554/eLife.07290

Share this article

https://doi.org/10.7554/eLife.07290

Further reading

    1. Neuroscience
    Daniel R Schonhaut, Aditya M Rao ... Michael J Kahana
    Research Article Updated

    Memory formation depends on neural activity across a network of regions, including the hippocampus and broader medial temporal lobe (MTL). Interactions between these regions have been studied indirectly using functional MRI, but the bases for interregional communication at a cellular level remain poorly understood. Here, we evaluate the hypothesis that oscillatory currents in the hippocampus synchronize the firing of neurons both within and outside the hippocampus. We recorded extracellular spikes from 1854 single- and multi-units simultaneously with hippocampal local field potentials (LFPs) in 28 neurosurgical patients who completed virtual navigation experiments. A majority of hippocampal neurons phase-locked to oscillations in the slow (2–4 Hz) or fast (6–10 Hz) theta bands, with a significant subset exhibiting nested slow theta × beta frequency (13–20 Hz) phase-locking. Outside of the hippocampus, phase-locking to hippocampal oscillations occurred only at theta frequencies and primarily among neurons in the entorhinal cortex and amygdala. Moreover, extrahippocampal neurons phase-locked to hippocampal theta even when theta did not appear locally. These results indicate that spike-time synchronization with hippocampal theta is a defining feature of neuronal activity in the hippocampus and structurally connected MTL regions. Theta phase-locking could mediate flexible communication with the hippocampus to influence the content and quality of memories.

    1. Developmental Biology
    2. Neuroscience
    Sergi Llambrich, Birger Tielemans ... Greetje Vande Velde
    Research Article

    Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, neurodevelopmental delay, hyperactivity, and impaired memory robustness with altered hippocampal metabolite concentration and gene expression. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of GTE-EGCG as a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.