Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington's nucleus CRH neurons

  1. Hiroki Ito
  2. Anna C Sales  Is a corresponding author
  3. Christopher H Fry
  4. Anthony J Kanai
  5. Marcus J Drake
  6. Anthony E Pickering  Is a corresponding author
  1. University of Bristol, United Kingdom
  2. University of Pittsburgh, United States

Abstract

Micturition requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. This involves a spino-bulbospinal control circuit incorporating Barrington's nucleus in the pons (Barr). Ponto-spinal glutamatergic neurons that express corticotrophin-releasing hormone (CRH) form one of the largest Barr cell populations. BarrCRH neurons can generate bladder contractions, but it is unknown whether they act as a simple switch or provide a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with multisite extracellular recordings in urethane anaesthetised CRHCre mice show that BarrCRH neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. CRH itself provides negative feedback regulation of this process. These findings inform a new inferential model of autonomous micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding.

Data availability

The data generated during this study are included either in the manuscript, in supporting files, or in the dataset deposited at the University of Bristol Research Data Repository at DOI:10.5523/bris.20l920gl27ufi204brn8ilonsf uk/data/.

The following data sets were generated
    1. Pickering A
    2. Sales A
    3. Ito H
    (2019) Ito, Sales et al 2019 Example BarrCRH recordings and analysis / model code
    University of Bristol Research Data Repository DOI:10.5523/bris.20l920gl27ufi204brn8ilonsf uk/data/.

Article and author information

Author details

  1. Hiroki Ito

    School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Anna C Sales

    School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
    For correspondence
    anna.sales@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8585-3763
  3. Christopher H Fry

    School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Anthony J Kanai

    Department of Medicine, Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Marcus J Drake

    School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Anthony E Pickering

    School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
    For correspondence
    tony.pickering@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0345-0456

Funding

National Institutes of Health (R01 DK098361)

  • Christopher H Fry
  • Anthony J Kanai
  • Marcus J Drake
  • Anthony E Pickering

Wellcome (108899/Z/15)

  • Anna C Sales

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

Ethics

Animal experimentation: All experiments and procedures conformed to the UK Animals (Scientific Procedures) Act 1986 and were approved by the University of Bristol Animal Welfare and Ethical review body. licence (PPL3003362).

Reviewing Editor

  1. Bernardo L Sabatini, Howard Hughes Medical Institute, Harvard Medical School, United States

Version history

  1. Received: March 3, 2020
  2. Accepted: April 28, 2020
  3. Accepted Manuscript published: April 29, 2020 (version 1)
  4. Version of Record published: May 12, 2020 (version 2)

Copyright

© 2020, Ito 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. Hiroki Ito
  2. Anna C Sales
  3. Christopher H Fry
  4. Anthony J Kanai
  5. Marcus J Drake
  6. Anthony E Pickering
(2020)
Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington's nucleus CRH neurons
eLife 9:e56605.
https://doi.org/10.7554/eLife.56605

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