Selective transduction and photoinhibition of pre-Bötzinger neurons that project to the facial nucleus in rats affect the nasofacial activity

  1. Mariana R Melo  Is a corresponding author
  2. Alexander D Wykes
  3. Angela A Connelly
  4. Jaspreet K Bassi
  5. Shane Doris Cheung
  6. Stuart J McDougall
  7. Clément Menuet
  8. Ross AD Bathgate
  9. Andrew M Allen  Is a corresponding author
  1. University of Melbourne, Australia
  2. Florey Institute of Neuroscience and Mental Health, Australia
  3. Institut de Neurobiologie de la Méditerranée, France

Abstract

The preBötzinger Complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 2, 3, 8, Figures 8 -supplement 1 and 3, and Figure 9

Article and author information

Author details

  1. Mariana R Melo

    Department of Anatomy and Physiology, University of Melbourne, Parkville, Australia
    For correspondence
    mariana.del@unimelb.edu.au
    Competing interests
    The authors declare that no competing interests exist.
  2. Alexander D Wykes

    Florey Institute of Neuroscience and Mental Health, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8264-7585
  3. Angela A Connelly

    Department of Anatomy and Physiology, University of Melbourne, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4547-4352
  4. Jaspreet K Bassi

    Department of Anatomy and Physiology, University of Melbourne, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Shane Doris Cheung

    Biological Optical Microscopy Platform, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8733-4756
  6. Stuart J McDougall

    Florey Institute of Neuroscience and Mental Health, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8778-675X
  7. Clément Menuet

    INSERM U1249, Institut de Neurobiologie de la Méditerranée, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7419-6427
  8. Ross AD Bathgate

    Florey Institute of Neuroscience and Mental Health, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Andrew M Allen

    Department of Anatomy and Physiology, University of Melbourne, Parkville, Australia
    For correspondence
    a.allen@unimelb.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2183-5360

Funding

Early Career Research - University of Melbourne (503275)

  • Mariana R Melo

Early Career Reasearch Transition Grant of Hypertension Australia Ltd (830365)

  • Mariana R Melo

Australian Research Council (DP231003058)

  • Andrew M Allen

National Health and Medical Research Council (1156727)

  • Andrew M Allen

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

Ethics

Animal experimentation: Experiments were conducted in accordance with the National Health and Medical Research Council of Australia's "Guidelines to promote the well-being of animals used for scientific purposes: The assessment and alleviation of pain and distress in research animals (2008)" and "Australian code for the care and use of animals for scientific purposes" and were approved by the University of Melbourne Animal Research Ethics and Biosafety Committees (ethics ID#21396).

Reviewing Editor

  1. Jeffrey C Smith, National Institute of Neurological Disorders and Stroke, United States

Version history

  1. Received: December 6, 2022
  2. Preprint posted: December 30, 2022 (view preprint)
  3. Accepted: September 28, 2023
  4. Accepted Manuscript published: September 29, 2023 (version 1)
  5. Version of Record published: November 16, 2023 (version 2)

Copyright

© 2023, Melo 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.

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  1. Mariana R Melo
  2. Alexander D Wykes
  3. Angela A Connelly
  4. Jaspreet K Bassi
  5. Shane Doris Cheung
  6. Stuart J McDougall
  7. Clément Menuet
  8. Ross AD Bathgate
  9. Andrew M Allen
(2023)
Selective transduction and photoinhibition of pre-Bötzinger neurons that project to the facial nucleus in rats affect the nasofacial activity
eLife 12:e85398.
https://doi.org/10.7554/eLife.85398

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