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...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2020-04-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/56605 |
_version_ | 1818019300764549120 |
---|---|
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. |
first_indexed | 2024-04-14T07:50:00Z |
format | Article |
id | doaj.art-0c06e6eb5467467295019736dc63134d |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-14T07:50:00Z |
publishDate | 2020-04-01 |
publisher | eLife Sciences Publications Ltd |
record_format | Article |
series | eLife |
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 |
work_keys_str_mv | AT hirokiito probabilisticspinallygatedcontrolofbladderpressureandautonomousmicturitionbybarringtonsnucleuscrhneurons AT annacsales probabilisticspinallygatedcontrolofbladderpressureandautonomousmicturitionbybarringtonsnucleuscrhneurons AT christopherhfry probabilisticspinallygatedcontrolofbladderpressureandautonomousmicturitionbybarringtonsnucleuscrhneurons AT anthonyjkanai probabilisticspinallygatedcontrolofbladderpressureandautonomousmicturitionbybarringtonsnucleuscrhneurons AT marcusjdrake probabilisticspinallygatedcontrolofbladderpressureandautonomousmicturitionbybarringtonsnucleuscrhneurons AT anthonyepickering probabilisticspinallygatedcontrolofbladderpressureandautonomousmicturitionbybarringtonsnucleuscrhneurons |