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W C De Groat - One of the best experts on this subject based on the ideXlab platform.

  • neural control of the urethra
    Scandinavian Journal of Urology and Nephrology, 2001
    Co-Authors: W C De Groat, Naoki Yoshimura, Matthew O Fraser, Mitsuharu Yoshiyama, S Smerin, Michael B Chancellor, J R Roppolo
    Abstract:

    Coordination between the urinary bladder and the urethra is mediated by multiple reflex pathways organized in the brain and spinal cord. Some reflexes promote urine storage; whereas other reflexes facilitate voiding. During bladder filling, activation of mechanoreceptor afferent nerves in the bladder wall triggers firing in the cholinergic efferent pathways to the external urethral sphincter (EUS) and in sympathetic adrenergic pathways to the urethral smooth muscle. These storage reflexes are dependent upon interneuronal circuitry in the spinal cord. During voiding the spinal storage reflexes are inhibited by supraspinal mechanisms which originate in the Pontine Micturition Center. Glutamatergic, serotonergic and alpha 1 adrenergic excitatory transmission as well as GABAergic/glycinergic inhibitory transmission have been implicated in the central control of sphincter reflexes. During voiding, a parasympathetic nitrergic inhibitory input to the urethral smooth is activated. This reflex mechanism which is t...

  • Non-NMDA glutamatergic excitatory transmission in the descending limb of the spinobulbospinal Micturition reflex pathway of the rat.
    Brain research, 1995
    Co-Authors: G Matsumoto, T Hisamitsu, W C De Groat
    Abstract:

    I.v. administration of GYKI-52466, a non-competitive AMPA/kainate glutamatergic receptor antagonist, inhibited bladder contractions elicited by electrical stimulation in the Pontine Micturition Center (PMC) in urethane-anesthetized rats. The mean threshold dose of GYKI-52466 was 2 mg/kg i.v. (range = 1-4 mg/kg). Maximum inhibition (mean = 57.7 +/- 8.2%, range = 24-83.3% of control) occurred at a dose of 8 mg/kg. CNQX, a competitive AMPA/kainate glutamatergic receptor antagonist, did not significantly alter the evoked contractions. These results indicate that AMPA/kainate receptors are involved in bulbospinal excitatory pathway from the PMC to the parasympathetic nucleus in the lumbosacral spinal cord in the rat.

  • Role of glutamate and NMDA receptors in the descending limb of the spinobulbospinal Micturition reflex pathway of the rat.
    Neuroscience letters, 1995
    Co-Authors: G Matsumoto, T Hisamitsu, W C De Groat
    Abstract:

    MK-801, an NMDA receptor antagonist administered intravenously or intrathecally to the L6-S1 spinal cord inhibited in a dose dependent manner the amplitude of isovolumetric bladder contractions evoked by electrical stimulation in the Pontine Micturition Center (PMC) in urethane anesthetized rats. The mean threshold dose of MK-801 was 10 +/- 6 micrograms/kg i.v. and 10 +/- 1 micrograms i.t. Bladder contractions were completely inhibited at doses ranging from 300 to 3000 micrograms/kg i.v. and from 18 to 48 micrograms i.t. These data indicate that NMDA glutamatergic receptors play an important role in excitatory transmission in the descending pathway from the PMC to the spinal segmental circuitry involved in the control of the urinary bladder.

  • Modulation of the spinobulbospinal Micturition reflex pathway in cats.
    American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1992
    Co-Authors: M.n. Kruse, H Noto, J R Roppolo, Brenda Mallory, W C De Groat
    Abstract:

    Micturition, which is mediated by a spinobulbospinal reflex pathway, can be modulated by various spinal and supraspinal mechanisms. This study examined modulation of the Micturition reflex in decerebrate unanesthetized cats. Electrical stimulation of the Pontine Micturition Center (PMC) elicited two types of bladder responses: small-amplitude short-duration responses due to direct activation of the bulbospinal pathway (PS-direct contractions) and large-amplitude long-duration reflex responses induced by PS-direct contractions but maintained by afferent feedback (PS-reflex contractions). Rectal and vaginal-cervical stimulation inhibited the PS-direct contractions, indicating inhibition of the descending or efferent limb of the Micturition pathway. Stimulation of the central end of a transected S2 ventral root elicited recurrent inhibition of PS-reflex contractions but not of PS-direct contractions, indicating that recurrent inhibition does not directly affect the descending pathway. Continuous electrical stimulation (20 Hz) of the PMC decreased (53 +/- 21%) bladder capacity, presumably by affecting transmission in the pons or ascending input to the pons. Thus the Micturition reflex could be modulated at several sites: the pons, the ascending or descending pathways, or spinal interneuronal sites.

  • Pharmacological modulation of the Pontine Micturition Center.
    Brain research, 1991
    Co-Authors: Brenda Mallory, J R Roppolo, W C De Groat
    Abstract:

    Abstract Previous studies have indicated that an area of the rostral Pontine tegmentum known as the ‘Pontine Micturition Center’ (PMC) plays an essential role in the regulation of lower urinary tract function. The present pharmacologic experiments were conducted on either decerebrate unanesthetized or chloralose anesthetized cats to identify the location of the PMC and to examine the neurotransmitter mechanism controlling Micturition. Microinjections of excitatory and inhibitory amino acids were made at stereotaxic coordinates P1 to P3, L2 to L3, H0 to H-4 where electrical stimulation with trains of pulses (2–30 V, 80–120 Hz and 50–300 ms train duration) elicited short latency ( L -glutamate (L-GLUT) (20–130 nmol) or DL -homocysteic acid (DLH) (20–100 nmol) into the region of the locus coeruleus or parabrachial nucleus elicited voiding as well as an increase in the frequency or amplitude of isovolumetric bladder contractions. In some anesthetized animals, L-GLUT and DLH also had mixed excitatory-inhibitory or pure inhibitory effects. Injections of muscimol (9–70 nmol) depressed rhythmic bladder activity, increased the bladder volume for inducing Micturition or completely abolished the voiding induced by bladder filling. The inhibitory effects of muscimol were reversed by microinjections of bicuculine methiodide (BCMI) (3–22 nmol). Injections of BCMI (1–1.5 nmol) into untreated cats stimulated bladder activity and lowered the bladder volume for inducing Micturition. It is concluded that: (1) neurons in the rostral pons are an essential component of the Micturition reflex pathway, (2) several populations of neurons located in the region of the locus coeruleus complex and parabrachial nucleus contribute to the functions of the PMC, and (3) PMC neurons are under a tonic GABAergic inhibitory control which regulates the Micturition threshold and in turn regulates bladder capacity.

Gert Holstege - One of the best experts on this subject based on the ideXlab platform.

  • Afferent projections to the Pontine Micturition Center in the cat.
    The Journal of comparative neurology, 2006
    Co-Authors: Rutger Kuipers, Leonora J. Mouton, Gert Holstege
    Abstract:

    The Pontine Micturition Center (PMC) or Barrington's nucleus controls Micturition by way of its descending projections to the sacral spinal cord. However, little is known about the afferents to the PMC that control its function and may be responsible for dysfunction in patients with urge-incontinence and overactive bladder. In five female cats, wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) injections were made in the PMC and adjoining dorsolateral Pontine tegmentum. Retrogradely labeled neurons were found in a large area, including the medullary and Pontine medial and lateral tegmental field; dorsomedial, lateral, and ventrolateral periaqueductal gray matter (PAG); posterior hypothalamus; medial preoptic area (MPO); bed nucleus of the stria terminalis; central nucleus of the amygdala; and infralimbic, prelimbic, and insular cortices. To verify whether these areas indeed project specifically to the PMC or perhaps only to adjacent structures in the Pontine tegmentum, in 67 cats (3)H-leucine or WGA-HRP injections were made in each of these regions. Five cell groups appeared to have direct connections to the PMC, the ventromedial pontomedullary tegmental field, the ventrolateral and dorsomedial PAG, the MPO, and the posterior hypothalamus. The possible functions of these projections are discussed. These results indicate that all other parts of the brain that influence Micturition have no direct connection with the PMC.

  • ultrastructural evidence for direct projections from the Pontine Micturition Center to glycine immunoreactive neurons in the sacral dorsal gray commissure in the cat
    The Journal of Comparative Neurology, 2001
    Co-Authors: Judith A M L Sie, Henk De Weerd, Bertil F.m. Blok, Gert Holstege
    Abstract:

    During Micturition, according to the concept of Blok, Holstege, and colleagues ([1997] Neurosci. Lett. 233:109-112), the Pontine Micturition Center (PMC) elicits bladder contraction by way of direct excitation of the parasympathetic bladder motoneurons. At the same time, the PMC elicits relaxation of the external urethral sphincter (EUS) by excitation of gamma -aminobutyric acid (GABA)-ergic interneurons in the sacral dorsal gray commissure (DGC), which, in turn, inhibit EUS motoneurons. The question is whether the inhibitory neurotransmitter glycine is also involved in this system. The present study investigated, first, whether there are glycine immunoreactive interneurons in the sacral DGC and, second, whether they receive direct PMC afferents. Finally, it was determined whether glycine and GABA are colocalized in DGC interneurons. In two adult male cats, the PMC was identified by electrical stimulation. Subsequently, the identified region was injected with the anterograde tracer WGA-HRP. Sections of sacral cord segments were processed for light and electron microscopic detection of anterograde labeling, as well as for glycine and GABA, using postembedding immunogold labeling with antibodies. In total 128 labeled PMC terminals were found in the DGC, which contained many round vesicles and asymmetric synapses. About 31.3% (40 of 128) made contact with glycine-immunoreactive dendrites. Eleven of them were selected for serial sectioning, which showed that 54.6% (6 of 11) of the glycine-immunoreactive dendrites were also immunoreactive for GABA. The results demonstrate that the PMC projects directly to dendrites of interneurons in the sacral DGC, which are immunoreactive for both glycine and GABA. These interneurons are thought to inhibit the EUS motoneurons during Micturition. J. Comp. Neurol. 429:631-637, 2001. (C) 2001 Wiley-Liss, Inc.

  • The Pontine Micturition Center in rat receives direct lumbosacral input. An ultrastructural study.
    Neuroscience Letters, 2000
    Co-Authors: Bertil F.m. Blok, Gert Holstege
    Abstract:

    The act of Micturition differs strongly among species. For example, adult cats and humans urinate primarily in a safe environment ('guarded urination'), while rats urinate more reflexively ('reflex urination'). This study in adult rats investigates the existence of direct lumbosacral cord projections to spinally projecting neurons in the Pontine Micturition Center (PMC). Bilateral injections of wheat germ agglutinin horseradish peroxidase in the caudal lumbar and rostral sacral cord resulted in labeled profiles, including retrogradely labeled neurons in the PMC. At the ultrastructural level, anterogradely labeled terminals in the PMC were found, which were filled with many round and some pleiomorphic and flat vesicles. About eleven percent of the terminals contacted retrogradely labeled dendrites. Of the labeled terminals 80% contained asymmetric synaptic clefts, and 20% symmetric synaptic clefts. The results provide evidence that in the rat, unlike the cat, a direct lumbosacral pathway to the PMC exists, which might explain the differences in Micturition behavior between rats and cats.

  • Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat
    Neuroscience letters, 1998
    Co-Authors: Bertil F.m. Blok, Jos Th. P. W. Van Maarseveen, Gert Holstege
    Abstract:

    Stimulation of the Pontine Micturition Center (PMC) results in Micturition, i.e. an immediate relaxation of the urethral sphincter and a contraction of the detrusor muscle of the bladder. The PMC generates the bladder contraction by way of a direct excitatory pathway to the parasympathetic bladder motoneurons in the sacral cord. The idea is that the PMC produces the relaxation of the urethral sphincter via direct projections to GABAergic neurons in the dorsal gray commissure (DGC), which, in turn, inhibit the urethral sphincter motoneurons. According to this hypothesis, electrical stimulation in the DGC in three cats should result in relaxation of the urethral sphincter. The results were in total agreement with this concept. During DGC stimulation a sharp decrease of the urethral pressure was found, the strength of which depended completely on the amplitude of the electrical stimulation.

  • The Central Control Of Micturition In Cats And Humans
    1998
    Co-Authors: Bertil F.m. Blok, Gert Holstege
    Abstract:

    Recent findings concerning the central control of Micturition in cats are compared to findings obtained from dynamic imaging studies in humans. In the cat, three areas in the brainstem and diencephalon are specifically implicated in the control of Micturition: (1) Barrington’s nucleus or the Pontine Micturition Center in the dorsomedial Pontine tegmentum directly excites bladder motoneurons and indirectly inhibits, via inhibitory interneurons in the medial sacral cord, urethral sphincter motoneurons; (2) the periaqueductal grey receiving bladder filling information; and (3) the pre-optic area of the hypothalamus possibly involved in determining the beginning of Micturition. According to PET-scan studies, in humans the same supraspinal regions are active during Micturition. In the cat another area, located in the ventrolateral Pontine tegmentum and is called the L-region, which controls the motoneurons of the pelvic floor, including the external urethral sphincter. This region might be considered as the Pontine storage Center. In humans the L-region is especially active in volunteers who tried but did not succeed to micturate. The results suggest that in cats and humans at the brainstem and diencephalic levels Micturition is organized in the same way.

Rose Khavari - One of the best experts on this subject based on the ideXlab platform.

  • functional magnetic resonance imaging during urodynamic testing identifies brain structures initiating Micturition
    The Journal of Urology, 2014
    Co-Authors: Michael E Shy, Sophie G Fletcher, Steve H Fung, Timothy B Boone, Christof Karmonik, Rose Khavari
    Abstract:

    Purpose Normal voiding in neurologically intact patients is triggered by the release of tonic inhibition from supraPontine Centers, allowing the Pontine Micturition Center to trigger the voiding reflex. Supraspinal mechanisms of voluntary voiding in humans are just beginning to be described via functional neuroimaging. We further elucidated brain activity processes during voiding using functional magnetic resonance imaging in normal females to gain better understanding of normal voiding as well as changes that may occur in voiding dysfunction. Materials and Methods We screened 13 healthy premenopausal female volunteers using baseline clinic urodynamics to document normal voiding parameters. We then recorded brain activity via functional magnetic resonance imaging and simultaneous urodynamics, including the pressure flow voiding phase. After motion correction of functional magnetic resonance images we performed activation and connectivity analyses in 10 subjects. Results Group analysis revealed consistent activation areas, including regions for motor control (cerebellum, thalamus, caudate, lentiform nucleus, red nucleus, supplementary motor area and post-central gyrus), emotion (anterior/posterior cingulate gyrus and insula), executive function (left superior frontal gyrus) and a focal region in the pons. Connectivity analysis demonstrated strong interconnectivity of the Pontine Micturition Center with many short-range and long-range cortical clusters. Conclusions Our study is one of the first reports of brain activation Centers associated with Micturition initiation in normal healthy females. Results show activation of a brain network consisting of regions for motor control, executive function and emotion processing. Further studies are planned to create and validate a model of brain activity during normal voiding in women.

  • functional magnetic resonance imaging during urodynamic testing identifies brain structures initiating Micturition
    The Journal of Urology, 2014
    Co-Authors: Michael E Shy, Steve H Fung, Christof Karmonik, Timothy Oone, Sophie G Fletche, Rose Khavari
    Abstract:

    Purpose: Normal voiding in neurologically intact patients is triggered by the release of tonic inhibition from supraPontine Centers, allowing the Pontine Micturition Center to trigger the voiding reflex. Supraspinal mechanisms of voluntary voiding in humans are just beginning to be described via functional neuroimaging. We further elucidated brain activity processes during voiding using functional magnetic resonance imaging in normal females to gain better understanding of normal voiding as well as changes that may occur in voiding dysfunction.Materials and Methods: We screened 13 healthy premenopausal female volunteers using baseline clinic urodynamics to document normal voiding parameters. We then recorded brain activity via functional magnetic resonance imaging and simultaneous urodynamics, including the pressure flow voiding phase. After motion correction of functional magnetic resonance images we performed activation and connectivity analyses in 10 subjects.Results: Group analysis revealed consistent...

Naoki Yoshimura - One of the best experts on this subject based on the ideXlab platform.

  • overview of pharmacological mechanisms controlling Micturition in the central nervous system
    Folia Pharmacologica Japonica, 2020
    Co-Authors: Naoki Yoshimura, Takeya Kitta, Katsumi Kadekawa, Minoru Miyazato, Takahiro Shimizu
    Abstract:

    The functions of the lower urinary tract, to storage and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra and external urethral sphincter. This activity is in turn controlled by neural circuits not only in the periphery, but also in the central nervous system (CNS). During urine storage, the outlet is closed and the bladder smooth muscle is quiescent by the neural control mechanism mainly organized in the spinal cord. When bladder volume reaches the Micturition threshold, activation of a Micturition Center in the dorsolateral pons (the Pontine Micturition Center) induces Micturition through activation of sacral parasympathetic (pelvic) nerves. The brain rostral to the pons (diencephalon and cerebral cortex) is also involved in excitatory and inhibitory regulation of the Micturition reflex. Various transmitters including dopamine, serotonin, norepenephrine, GABA, excitatory and inhibitory amino acids, opioids and acetylcholine are implicated in the modulation of the Micturition reflex in the CNS. Therefore, injury or neurodegenerative diseases of the CNS as well as drugs can produce bladder and urethral dysfunctions such as urinary frequency, urgency and incontinence or inefficient bladder emptying.

  • Review Article Neural Mechanisms Underlying Lower Urinary Tract Dysfunction
    2016
    Co-Authors: Naoki Yoshimura, Takeya Kitta, Minoru Miyazato, Michael B Chancellor, Teruyuki Ogawa, Akira Furuta, Pradeep Tyagi
    Abstract:

    This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neuro-transmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the Micturition threshold, activation of a Micturition Center in the dorsolateral pons (the Pontine Micturition Center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and pu-rinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as dis-orders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed

  • Anatomy and physiology of the lower urinary tract.
    Handbook of clinical neurology, 2015
    Co-Authors: William C. De Groat, Naoki Yoshimura
    Abstract:

    Functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. Neural control of Micturition is organized as a hierarchic system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brainstem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brainstem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the Micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and Pontine Micturition Center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of Micturition is described. Micturition occurs involuntarily during the early postnatal period, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults cause re-emergence of involuntary Micturition, leading to urinary incontinence. The mechanisms underlying these pathologic changes are discussed.

  • Neural Mechanisms Underlying Lower Urinary Tract Dysfunction
    Korean journal of urology, 2014
    Co-Authors: Naoki Yoshimura, Takeya Kitta, Minoru Miyazato, Michael B Chancellor, Teruyuki Ogawa, Akira Furuta, Pradeep Tyagi
    Abstract:

    This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the Micturition threshold, activation of a Micturition Center in the dorsolateral pons (the Pontine Micturition Center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed.

  • New insights into neural mechanisms controlling the Micturition reflex
    Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 2003
    Co-Authors: Naoki Yoshimura
    Abstract:

    The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. This activity is in turn controlled by neural circuits in the brain, spinal cord, and peripheral ganglia. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the Micturition threshold, activation of a Micturition Center in the dorsolateral pons (the Pontine Micturition Center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. The brain rostral to the pons (diencephalon and cerebral cortex) is also involved in excitatory and inhibitory regulation of the Micturition reflex. Various transmitters including dopamine, serotonin, norepinephrine, GABA, excitatory and inhibitory amino acids, opioids, acetylcholine, and neuropeptides are implicated in the modulation of the Micturition reflex in the central nervous system. Therefore, injury or diseases of the nervous system, as well as drugs and disorders of the peripheral organs, can produce bladder and urethral dysfunctions such as urinary frequency, urgency and incontinence, or inefficient bladder emptying.

Bertil F.m. Blok - One of the best experts on this subject based on the ideXlab platform.

  • Central Pathways That Control the Urinary Bladder
    Neurourology, 2019
    Co-Authors: Bertil F.m. Blok
    Abstract:

    In order to understand the role of the brain in the control of the urinary bladder and its sphincter, it is important to make a distinction between (1) Areas and pathways which are intrinsic part of the Micturition and continence reflex, and (2) Areas and pathways which modulate these Micturition and continence areas. Most of the clinical therapies aimed at alleviating functional bladder disorders are not specifically targeted on the central reflex areas, like the Pontine Micturition Center (PMC), but influence cortical and subcortical brain areas which modulate the Micturition reflex components. This chapter gives an overview of the central areas involved in the control of Micturition and continence and highlights their role in the pathophysiology of functional bladder problems.

  • ultrastructural evidence for direct projections from the Pontine Micturition Center to glycine immunoreactive neurons in the sacral dorsal gray commissure in the cat
    The Journal of Comparative Neurology, 2001
    Co-Authors: Judith A M L Sie, Henk De Weerd, Bertil F.m. Blok, Gert Holstege
    Abstract:

    During Micturition, according to the concept of Blok, Holstege, and colleagues ([1997] Neurosci. Lett. 233:109-112), the Pontine Micturition Center (PMC) elicits bladder contraction by way of direct excitation of the parasympathetic bladder motoneurons. At the same time, the PMC elicits relaxation of the external urethral sphincter (EUS) by excitation of gamma -aminobutyric acid (GABA)-ergic interneurons in the sacral dorsal gray commissure (DGC), which, in turn, inhibit EUS motoneurons. The question is whether the inhibitory neurotransmitter glycine is also involved in this system. The present study investigated, first, whether there are glycine immunoreactive interneurons in the sacral DGC and, second, whether they receive direct PMC afferents. Finally, it was determined whether glycine and GABA are colocalized in DGC interneurons. In two adult male cats, the PMC was identified by electrical stimulation. Subsequently, the identified region was injected with the anterograde tracer WGA-HRP. Sections of sacral cord segments were processed for light and electron microscopic detection of anterograde labeling, as well as for glycine and GABA, using postembedding immunogold labeling with antibodies. In total 128 labeled PMC terminals were found in the DGC, which contained many round vesicles and asymmetric synapses. About 31.3% (40 of 128) made contact with glycine-immunoreactive dendrites. Eleven of them were selected for serial sectioning, which showed that 54.6% (6 of 11) of the glycine-immunoreactive dendrites were also immunoreactive for GABA. The results demonstrate that the PMC projects directly to dendrites of interneurons in the sacral DGC, which are immunoreactive for both glycine and GABA. These interneurons are thought to inhibit the EUS motoneurons during Micturition. J. Comp. Neurol. 429:631-637, 2001. (C) 2001 Wiley-Liss, Inc.

  • The Pontine Micturition Center in rat receives direct lumbosacral input. An ultrastructural study.
    Neuroscience Letters, 2000
    Co-Authors: Bertil F.m. Blok, Gert Holstege
    Abstract:

    The act of Micturition differs strongly among species. For example, adult cats and humans urinate primarily in a safe environment ('guarded urination'), while rats urinate more reflexively ('reflex urination'). This study in adult rats investigates the existence of direct lumbosacral cord projections to spinally projecting neurons in the Pontine Micturition Center (PMC). Bilateral injections of wheat germ agglutinin horseradish peroxidase in the caudal lumbar and rostral sacral cord resulted in labeled profiles, including retrogradely labeled neurons in the PMC. At the ultrastructural level, anterogradely labeled terminals in the PMC were found, which were filled with many round and some pleiomorphic and flat vesicles. About eleven percent of the terminals contacted retrogradely labeled dendrites. Of the labeled terminals 80% contained asymmetric synaptic clefts, and 20% symmetric synaptic clefts. The results provide evidence that in the rat, unlike the cat, a direct lumbosacral pathway to the PMC exists, which might explain the differences in Micturition behavior between rats and cats.

  • Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat
    Neuroscience letters, 1998
    Co-Authors: Bertil F.m. Blok, Jos Th. P. W. Van Maarseveen, Gert Holstege
    Abstract:

    Stimulation of the Pontine Micturition Center (PMC) results in Micturition, i.e. an immediate relaxation of the urethral sphincter and a contraction of the detrusor muscle of the bladder. The PMC generates the bladder contraction by way of a direct excitatory pathway to the parasympathetic bladder motoneurons in the sacral cord. The idea is that the PMC produces the relaxation of the urethral sphincter via direct projections to GABAergic neurons in the dorsal gray commissure (DGC), which, in turn, inhibit the urethral sphincter motoneurons. According to this hypothesis, electrical stimulation in the DGC in three cats should result in relaxation of the urethral sphincter. The results were in total agreement with this concept. During DGC stimulation a sharp decrease of the urethral pressure was found, the strength of which depended completely on the amplitude of the electrical stimulation.

  • The Central Control Of Micturition In Cats And Humans
    1998
    Co-Authors: Bertil F.m. Blok, Gert Holstege
    Abstract:

    Recent findings concerning the central control of Micturition in cats are compared to findings obtained from dynamic imaging studies in humans. In the cat, three areas in the brainstem and diencephalon are specifically implicated in the control of Micturition: (1) Barrington’s nucleus or the Pontine Micturition Center in the dorsomedial Pontine tegmentum directly excites bladder motoneurons and indirectly inhibits, via inhibitory interneurons in the medial sacral cord, urethral sphincter motoneurons; (2) the periaqueductal grey receiving bladder filling information; and (3) the pre-optic area of the hypothalamus possibly involved in determining the beginning of Micturition. According to PET-scan studies, in humans the same supraspinal regions are active during Micturition. In the cat another area, located in the ventrolateral Pontine tegmentum and is called the L-region, which controls the motoneurons of the pelvic floor, including the external urethral sphincter. This region might be considered as the Pontine storage Center. In humans the L-region is especially active in volunteers who tried but did not succeed to micturate. The results suggest that in cats and humans at the brainstem and diencephalic levels Micturition is organized in the same way.