scholarly journals Corticotrophin-Releasing Hormone neurons of Barrington’s nucleus: Probabilistic, spinally-gated control of bladder pressure and micturition

2019 ◽  
Author(s):  
H. Ito ◽  
A.C. Sales ◽  
C.H. Fry ◽  
A.J. Kanai ◽  
M.J. Drake ◽  
...  

AbstractMicturition, the co-ordinated process of expulsion of urine from the bladder, requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. In adult mammals this involves a spinobulbospinal control circuit incorporating Barrington’s nucleus in the pons (Barr). The largest Barr cell population is comprised of pontospinal glutamatergic neurons that express corticotrophin-releasing hormone. There is evidence that BarrCRH neurons can generate bladder contractions but it is unknown whether they act as a simple switch or a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with recordings in mice shows that BarrCRH neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. These findings inform a new inferential model of micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding.

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Hiroki Ito ◽  
Anna C Sales ◽  
Christopher H Fry ◽  
Anthony J Kanai ◽  
Marcus J Drake ◽  
...  

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.


2021 ◽  
Author(s):  
Gopakumar K

<div>This paper proposes a novel and computationally efficient selective harmonic elimination (SHE) technique which eliminates the predefined lower order harmonics (till 19th order) from the phase voltage while controlling its fundamental. In conventional SHE schemes, the notch angles need to be computed online for each frequency in order to eliminate the harmonics and control the fundamental value. This involves intensive online computations and the convergence to the correct notch angles is not guaranteed, resulting in incorrect fundamental and/or presence of lower order harmonics. In contrast to this, a SHE technique, that uses the same pre-computed notch angles for all modulation indices, is proposed in this paper, thereby significantly reducing the computational burden. Here, the control of fundamental voltage at different frequencies is ensured by the concept of phase shifting of two identical notched waveforms. This ensures precise control of fundamental voltage while completely eliminating the pre-defined lower order harmonics. Moreover, the proposed scheme exhibits linear control till 0.582 times the DC-link voltage compared to 0.577 times the DC-link voltage in case of space vector PWM. The proposed method is validated experimentally on an induction motor drive system.</div>


2005 ◽  
Vol 93 (5) ◽  
pp. 2688-2697 ◽  
Author(s):  
Joseph W. Boggs ◽  
Brian J. Wenzel ◽  
Kenneth J. Gustafson ◽  
Warren M. Grill

Reflexes mediated by urethral sensory pathways are integral to urinary function. This study investigated the changes in bladder pressure and urethral sphincter activity resulting from electrical stimulation of afferents in the deep perineal nerve (DP), which innervates the urethra and surrounding muscles, before and after acute spinal cord transection (SCT) in cats anesthetized with α-chloralose monitored by blood pressure and heart rate. DP stimulation elicited bladder contractions before and after SCT but only if the bladder contained a sufficient volume of fluid (78% of the volume needed to cause distention-evoked reflex contractions). The volume dependency was mediated by a neuronal mechanism in the lumbosacral spinal cord and was not attributable to length-tension properties of the detrusor muscle. Stimulation at 2–40 Hz initiated bladder contractions, but 20–40 Hz was more effective than lower frequencies in evoking and sustaining bladder contractions for the duration of the stimulus train. Decreases in urethral sphincter activity occurred during sustained bladder contractions evoked by 20- to 40-Hz stimulation before and within 16 h after SCT. After SCT, average bladder pressure increases evoked by DP stimulation were smaller than those evoked before SCT, but in some animals, bladder pressures elicited by DP stimulation continued to increase as time after SCT increased and reached pretransection amplitudes at 8–16 h posttransection. These data confirm the presence of a spinal circuit that can mediate coordinated bladder–sphincter responses and show that afferents from the DP can activate this circuit under appropriate conditions.


2018 ◽  
Author(s):  
Jason Keller ◽  
Jingyi Chen ◽  
Sierra Simpson ◽  
Eric Hou-Jen Wang ◽  
Varoth Lilascharoen ◽  
...  

Urination may occur either reflexively in response to a full bladder or deliberately irrespective of immediate need. Voluntary control is desired because it ensures that waste is expelled when consciously desired and socially appropriate1,2. Urine release requires two primary components: bladder pressure and urethral relaxation1–3. Although the bladder contracts during urination, its slow smooth muscle is not under direct voluntary control and its contraction alone is not sufficient for voiding. The decisive action of urination is at the urethral sphincter, where striated muscle permits fast control. This sphincter is normally constricted, but relaxes to enable urine flow. Barrington’s nucleus (Bar, or pontine micturition center) in the brainstem is known to be essential for the switch from urine storage to elimination4–7, and a subset of Bar neurons expressing corticotropin releasing hormone (BarCRH) have recently been shown to promote bladder contraction8–10. However, Bar neurons that relax the urethral sphincter to enable urination behavior have not been identified. Here we describe novel brainstem neurons that control the external urethral sphincter. We find that scent marking behavior in male mice depends upon a subpopulation of spatially clustered Bar neurons that express high levels of estrogen receptor 1 (BarESR1). These neurons are glutamatergic, project to urinary nuclei in the spinal cord with a bias towards sphincter-inhibiting interneurons, and their activity correlates with natural urination. Optogenetic stimulation of BarESR1 neurons rapidly initiates sphincter bursting and efficient voiding in absence of sensory cues in anesthetized and behaving animals. Conversely, inhibiting the activity of these neurons prevents olfactory cues from promoting scent marking behavior. The identification of BarESR1 cells provides an expanded model for the supraspinal control of urination and its dysfunction.


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