Urodynamics: How the brain controls urination
The brain and the bladder must communicate to make sure that we only urinate when and where it is appropriate. The process of urination is partly controlled by reflexes and is partly under conscious control (de Groat et al., 2015). As the bladder fills, it sends sensory information to the central nervous system, and when the bladder is full, these signals indicate that it must be emptied soon.
One of the signals going the other way, from the brain to the bladder, is the activation of a part of the brainstem called the PMC, short for pontine micturition center. (The word 'micturition' originally referred to the urge to urinate, but is now often used to describe the process of urination as well). The PMC connects to other centers in the central and peripheral nervous systems to coordinate when urination occurs (Fowler et al., 2008). Many studies have identified and examined the main brain centers involved in the control of urination. However, the connections between these different centers, including when and for how long they become active, remain elusive. It is also unclear how the cortex – the part of the brain responsible for higher thought processes – influences urination.
Now, in eLife, Rita Valentino of the Children’s Hospital of Philadelphia and co-workers – including Anitha Manohar as first author – report how neuronal activity is orchestrated before, during and after urination in rats (Manohar et al., 2017). The researchers evaluated when and where neurons fired in unanesthetized rats as their bladders filled and then emptied by recording neural activity in three regions of the brain that are involved in urination: the PMC, the locus coeruleus, and the medial prefrontal cortex (mPFC; Figure 1). At the same time, they measured both the pressure within the bladder and the frequency of urine output.
First, Manohar et al. established that all neurons in the PMC show the same firing patterns, characterized by slow background activity and fast bursts during the intervals between urinations. These bursts became rare prior to urination, more prominent during urination, and continued for several seconds after the bladder had been emptied. This timing of neuronal activity suggests that PMC neurons likely play a more complex role in regulating the emptying of the bladder than a simple 'on-off switch'. The bursts of activity in the PMC during the intervals between urinations were also intriguing. It was previously believed that PMC neurons were only active during urination (Betts et al., 1992).
In the seconds before urination, neurons in the locus coeruleus showed ongoing low frequency bursts with stronger theta oscillations (waves of activity that repeat about seven times per second). At the same time, the activity in the locus coeruleus started to more closely match that in the mPFC, though the activity across the mPFC became less synchronized. It is likely that some of these changes help to begin the process of urination by increasing arousal and shifting attention toward the full bladder (Michels et al., 2015).
The relationship between the locus coeruleus (LC) and the PMC is also interesting. These centers are close enough that neuronal activity could be recorded from both regions at the same time. The results showed that LC neurons were activated before PMC neurons, suggesting that the former receives indirect input from the bladder before the stimulus reaches the PMC. This is consistent with earlier observations using fMRI in rats (Tai et al., 2009).
The new findings reported by Manohar et al. raise a few questions. The roles of the brainstem and the cortex in processing information from the bladder, and in coordinating urination, remain unclear. It is also not obvious why PMC neurons show bursts of activity in the intervals between urinations. Recent data suggest that there are different kinds of neurons in the PMC (Figure 1), so it is possible that a specific population of PMC neurons sends signals that help the bladder store urine by releasing different types of neurotransmitters (Hou et al., 2016). Earlier studies also showed that urine storage reflexes are mainly organized in the spinal cord (Drake et al., 2010). However, a group of neurons located in the brainstem might play a role in urine storage too. When activated, these neurons made the external urethral sphincter – the muscle that allows us to choose to start urination – more active (Blok and Holstege, 1999).
We need more data about the pathways through which the locus coeruleus receives information from the bladder before it is transmitted to the PMC. Future experiments should also explore what other regions of the cortex get synchronized or desynchronized during urination. Manohar et al. speculate in these areas, based on the published literature, but further studies are clearly warranted to provide more definitive answers.
References
-
Pontine pathology and voiding dysfunctionBritish Journal of Urology 70:100–102.https://doi.org/10.1111/j.1464-410X.1992.tb15679.x
-
Neural control of the lower urinary tractComprehensive Physiology 5:327–396.https://doi.org/10.1002/cphy.c130056
-
Neural control of the lower urinary and gastrointestinal tracts: supraspinal CNS mechanismsNeurourology and Urodynamics 29:119–127.https://doi.org/10.1002/nau.20841
-
The neural control of micturitionNature Reviews Neuroscience 9:453–466.https://doi.org/10.1038/nrn2401
-
Supraspinal control of urine storage and micturition in men—an fMRI studyCerebral Cortex 25:3369–3380.https://doi.org/10.1093/cercor/bhu140
-
Brain switch for reflex micturition control detected by fMRI in ratsJournal of Neurophysiology 102:2719–2730.https://doi.org/10.1152/jn.00700.2009
Article and author information
Author details
Publication history
Copyright
© 2017, Malykhina
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,342
- views
-
- 224
- downloads
-
- 12
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Cell Biology
- Neuroscience
The assembly and maintenance of neural circuits is crucial for proper brain function. Although the assembly of brain circuits has been extensively studied, much less is understood about the mechanisms controlling their maintenance as animals mature. In the olfactory system, the axons of olfactory sensory neurons (OSNs) expressing the same odor receptor converge into discrete synaptic structures of the olfactory bulb (OB) called glomeruli, forming a stereotypic odor map. The OB projection neurons, called mitral and tufted cells (M/Ts), have a single dendrite that branches into a single glomerulus, where they make synapses with OSNs. We used a genetic method to progressively eliminate the vast majority of M/T cells in early postnatal mice, and observed that the assembly of the OB bulb circuits proceeded normally. However, as the animals became adults the apical dendrite of remaining M/Ts grew multiple branches that innervated several glomeruli, and OSNs expressing single odor receptors projected their axons into multiple glomeruli, disrupting the olfactory sensory map. Moreover, ablating the M/Ts in adult animals also resulted in similar structural changes in the projections of remaining M/Ts and axons from OSNs. Interestingly, the ability of these mice to detect odors was relatively preserved despite only having 1–5% of projection neurons transmitting odorant information to the brain, and having highly disrupted circuits in the OB. These results indicate that a reduced number of projection neurons does not affect the normal assembly of the olfactory circuit, but induces structural instability of the olfactory circuitry of adult animals.
-
- Neuroscience
Specialized chemosensory signals elicit innate social behaviors in individuals of several vertebrate species, a process that is mediated via the accessory olfactory system (AOS). The AOS comprising the peripheral sensory vomeronasal organ has evolved elaborate molecular and cellular mechanisms to detect chemo signals. To gain insight into the cell types, developmental gene expression patterns, and functional differences amongst neurons, we performed single-cell transcriptomics of the mouse vomeronasal sensory epithelium. Our analysis reveals diverse cell types with gene expression patterns specific to each, which we made available as a searchable web resource accessed from https://www.scvnoexplorer.com. Pseudo-time developmental analysis indicates that neurons originating from common progenitors diverge in their gene expression during maturation with transient and persistent transcription factor expression at critical branch points. Comparative analysis across two of the major neuronal subtypes that express divergent GPCR families and the G-protein subunits Gnai2 or Gnao1, reveals significantly higher expression of endoplasmic reticulum (ER) associated genes within Gnao1 neurons. In addition, differences in ER content and prevalence of cubic membrane ER ultrastructure revealed by electron microscopy, indicate fundamental differences in ER function.