Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing

  1. Arnaud Pautrat
  2. Marta Rolland
  3. Margaux Barthelemy
  4. Christelle Baunez
  5. Valérie Sinniger
  6. Brigitte Piallat
  7. Marc Savasta
  8. Paul G Overton
  9. Olivier David
  10. Veronique Coizet  Is a corresponding author
  1. INSERM, France
  2. Aix-Marseille Université, France
  3. University Grenoble Alpes, France
  4. University of Sheffield, United Kingdom

Abstract

Pain is a prevalent symptom of Parkinson's disease, and is effectively treated by deep brain stimulation of the subthalamic nucleus (STN). However, the link between pain and the STN remains unclear. In the present work, we report that STN neurons exhibit complex tonic and phasic responses to noxious stimuli using in vivo electrophysiology in rats. We also show that nociception is altered following lesions of the STN, and characterize the role of the superior colliculus and the parabrachial nucleus in the transmission of nociceptive information to the STN, physiologically from both structures and anatomically in the case of the parabrachial nucleus. We show that STN nociceptive responses are abnormal in a rat model of PD, suggesting their dependence on the integrity of the nigrostriatal dopaminergic system. The STN-linked nociceptive network we reveal is likely to be of considerable clinical importance in neurological diseases involving a dysfunction of the basal ganglia.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Matlab scripts used to analyse the data are freely available on the ImaGIN platform website (https://f-tract.eu/software/imagin/).

Article and author information

Author details

  1. Arnaud Pautrat

    U1216, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Marta Rolland

    U1216, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Margaux Barthelemy

    U1216, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Christelle Baunez

    Institut de Neurosciences Timone UMR7289, Aix-Marseille Université, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4368-652X
  5. Valérie Sinniger

    Grenoble Institute of Neurosciences, University Grenoble Alpes, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Brigitte Piallat

    U1216, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Marc Savasta

    U1216, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Paul G Overton

    Department of Psychology, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Olivier David

    U1216, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Veronique Coizet

    U1216, INSERM, Grenoble, France
    For correspondence
    veronique.coizet@univ-grenoble-alpes.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5192-6610

Funding

Institut National de la Santé et de la Recherche Médicale

  • Veronique Coizet

ADR Région Rhône Alpes

  • Veronique Coizet

UGA AGIR-POLE

  • Veronique Coizet

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

Ethics

Animal experimentation: In accordance with the policy of Lyon1 University, the Grenoble Institut des Neurosciences (GIN) and the French legislation, experiments were done in compliance with the European Community Council Directive of November 24, 1986 (86/609/EEC). The research was authorized by the Direction Départementale des Services Vétérinaires de l'Isère - Ministère de l'Agriculture et de la Pêche, France (Coizet Véronique, PhD, permit number 381003). Every effort was made to minimize the number of animals used and their suffering during the experimental procedure. All procedures were reviewed and validated by the ""Comité éthique du GIN no 004"" agreed by the research ministry (permits number 309 and 310).

Copyright

© 2018, Pautrat 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

  • 2,865
    views
  • 468
    downloads
  • 32
    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. Arnaud Pautrat
  2. Marta Rolland
  3. Margaux Barthelemy
  4. Christelle Baunez
  5. Valérie Sinniger
  6. Brigitte Piallat
  7. Marc Savasta
  8. Paul G Overton
  9. Olivier David
  10. Veronique Coizet
(2018)
Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing
eLife 7:e36607.
https://doi.org/10.7554/eLife.36607

Share this article

https://doi.org/10.7554/eLife.36607

Further reading

    1. Neuroscience
    Sharon Inberg, Yael Iosilevskii ... Benjamin Podbilewicz
    Research Article

    Dendrites are crucial for receiving information into neurons. Sensory experience affects the structure of these tree-like neurites, which, it is assumed, modifies neuronal function, yet the evidence is scarce, and the mechanisms are unknown. To study whether sensory experience affects dendritic morphology, we use the Caenorhabditis elegans' arborized nociceptor PVD neurons, under natural mechanical stimulation induced by physical contacts between individuals. We found that mechanosensory signals induced by conspecifics and by glass beads affect the dendritic structure of the PVD. Moreover, developmentally isolated animals show a decrease in their ability to respond to harsh touch. The structural and behavioral plasticity following sensory deprivation are functionally independent of each other and are mediated by an array of evolutionarily conserved mechanosensory amiloride-sensitive epithelial sodium channels (degenerins). Calcium imaging of the PVD neurons in a micromechanical device revealed that controlled mechanical stimulation of the body wall produces similar calcium dynamics in both isolated and crowded animals. Our genetic results, supported by optogenetic, behavioral, and pharmacological evidence, suggest an activity-dependent homeostatic mechanism for dendritic structural plasticity, that in parallel controls escape response to noxious mechanosensory stimuli.

    1. Neuroscience
    Raven Star Wallace, Bronte Mckeown ... Jonathan Smallwood
    Research Article

    Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the ‘here and now’ depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better—on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi-modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films.