Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington's nucleus CRH neurons
- University of Bristol, United Kingdom
- 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/.
-
Ito, Sales et al 2019 Example BarrCRH recordings and analysis / model codeUniversity of Bristol Research Data Repository DOI:10.5523/bris.20l920gl27ufi204brn8ilonsf uk/data/.
Article and author information
Author details
Anthony E Pickering
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).
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.
Metrics
-
- 2,014
- views
-
- 349
- downloads
-
- 22
- 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)
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
Further reading
-
- Neuroscience
Dopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly Drosophila melanogaster, Dop1R1 and Dop2R encode the D1- and D2-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and subcellular localization of endogenous Dop1R1 and Dop2R in specific cell types in the mushroom body circuit. For cell-type-specific visualization of endogenous proteins, we employed reconstitution of split-GFP tagged to the receptor proteins. We detected dopamine receptors at both presynaptic and postsynaptic sites in multiple cell types. Quantitative analysis revealed enrichment of both receptors at the presynaptic sites, with Dop2R showing a greater degree of localization than Dop1R1. The presynaptic localization of Dop1R1 and Dop2R in dopamine neurons suggests dual feedback regulation as autoreceptors. Furthermore, we discovered a starvation-dependent, bidirectional modulation of the presynaptic receptor expression in the protocerebral anterior medial (PAM) and posterior lateral 1 (PPL1) clusters, two distinct subsets of dopamine neurons, suggesting their roles in regulating appetitive behaviors. Our results highlight the significance of the co-expression of the two opposing dopamine receptors in the spatial and conditional regulation of dopamine responses in neurons.
-
- Neuroscience
The entorhinal cortex (EC) plays a pivotal role in memory function and spatial navigation, connecting the hippocampus with the neocortex. The EC integrates a wide range of cortical and subcortical inputs, but its synaptic organization in the human brain is largely unknown. We used volume electron microscopy to perform a 3D analysis of the microanatomical features of synapses in all layers of the medial EC (MEC) from the human brain. Using this technology, 12,974 synapses were fully 3D reconstructed at the ultrastructural level. The MEC presented a distinct set of synaptic features, differentiating this region from other human cortical areas. Furthermore, ultrastructural synaptic characteristics within the MEC was predominantly similar, although layers I and VI exhibited several synaptic characteristics that were distinct from other layers. The present study constitutes an extensive description of the synaptic characteristics of the neuropil of all layers of the EC, a crucial step to better understand the connectivity of this cortical region, in both health and disease.
