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

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-rel...

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Main Authors: Hiroki Ito, Anna C Sales, Christopher H Fry, Anthony J Kanai, Marcus J Drake, Anthony E Pickering
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-04-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/56605
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author Hiroki Ito
Anna C Sales
Christopher H Fry
Anthony J Kanai
Marcus J Drake
Anthony E Pickering
author_facet Hiroki Ito
Anna C Sales
Christopher H Fry
Anthony J Kanai
Marcus J Drake
Anthony E Pickering
author_sort Hiroki Ito
collection DOAJ
description 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.
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spelling doaj.art-0c06e6eb5467467295019736dc63134d2022-12-22T02:05:13ZengeLife Sciences Publications LtdeLife2050-084X2020-04-01910.7554/eLife.56605Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington’s nucleus CRH neuronsHiroki Ito0Anna C Sales1https://orcid.org/0000-0001-8585-3763Christopher H Fry2Anthony J Kanai3Marcus J Drake4Anthony E Pickering5https://orcid.org/0000-0003-0345-0456School of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, United Kingdom; Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, JapanSchool of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, United KingdomSchool of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, United KingdomDepartment of Medicine and Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, United StatesSchool of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, United Kingdom; Bristol Urology Institute, Bristol Medical School, University of Bristol, Bristol, United KingdomSchool of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, United Kingdom; Anaesthetic, Pain and Critical Care research group, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United KingdomMicturition 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.https://elifesciences.org/articles/56605barrington's nucleusmicturitionbladderbrainstem
spellingShingle Hiroki Ito
Anna C Sales
Christopher H Fry
Anthony J Kanai
Marcus J Drake
Anthony E Pickering
Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington’s nucleus CRH neurons
eLife
barrington's nucleus
micturition
bladder
brainstem
title Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington’s nucleus CRH neurons
title_full Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington’s nucleus CRH neurons
title_fullStr Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington’s nucleus CRH neurons
title_full_unstemmed Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington’s nucleus CRH neurons
title_short Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington’s nucleus CRH neurons
title_sort probabilistic spinally gated control of bladder pressure and autonomous micturition by barrington s nucleus crh neurons
topic barrington's nucleus
micturition
bladder
brainstem
url https://elifesciences.org/articles/56605
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