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B F Blok

Publications and source records attributed to B F Blok.

At least 19 recordsLinked to original sources

Ultrastructural evidence for direct projections from the pontine micturition center to glycine-immunoreactive neurons in the sacral dorsal gray commissure in the cat.

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.

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The pontine micturition center in rat receives direct lumbosacral input. An ultrastructural study.

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.

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Two pontine micturition centers in the cat are not interconnected directly: implications for the central organization of micturition.

The urinary bladder muscle and its external urethral sphincter are innervated, respectively, by the parasympathetic preganglionic motoneurons in the sacral intermediolateral cell column and somatic motoneurons in Onuf's nucleus. Neurons coordinating the activity of these muscles during micturition and urinary continence are not located in the sacral cord but in two pontine regions, the medial (M)-region (or pontine micturition center) and the lateral (L)-region (or pontine storage center). The M-region excites the bladder muscle through projections to its motoneurons and inhibits the urethral sphincter through excitatory projections to sacral cord gamma-amino butyric acid (GABA)-immunoreactive interneurons, which, in turn, inhibit urethral sphincter motoneurons. The L-region, through direct projections, excites urethral sphincter motoneurons. The present study investigated whether there are interconnections between the M- and L-regions. Anterograde tracing injections in the M-region resulted in labeled fibers to the intermediolateral cell column containing bladder motoneurons but not to Onuf's nucleus. No specific projections were found to the L-regions or to the contralateral M-region. L-region injections resulted in distinct projections to the Onuf's nucleus but not to the sacral intermediolateral cell column. No specific projections were observed either to the M-region or to the contralateral L-region. In conclusion, the M- and L-regions have direct long fiber projections, respectively, to the motoneurons of the bladder muscle and the external urethral sphincter, but they do not influence one another through direct pathways. The results strongly suggest that the M- and L-regions represent separate functional systems that act independently.

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Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat.

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.

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Premature ejaculation and serotonergic antidepressants-induced delayed ejaculation: the involvement of the serotonergic system.

Premature ejaculation has generally been considered a psychosexual disorder with psychogenic aetiology. Although still mainly treated by behavioural therapy, in recent years double-blind studies have indicated the beneficial effects of some of the serotonergic antidepressants (SSRIs) in delaying ejaculation. We describe here the neurophysiology and the peripheral neuroanatomy of ejaculation and provide a review of the involvement of serotonin in the central nervous system in relation to serotonergic nuclei and their projections. A hypothesis of the role of 5-HT1A and 5-HT2C receptors in premature ejaculation is postulated.

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The central nervous system control of micturition in cats and humans.

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.

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Brain activation during micturition in women.

Experiments in the cat have led to a concept of how the CNS controls micturition. In a previous study this concept was tested in a PET study in male volunteers. It was demonstrated that specific brainstem and forebrain areas are activated during micturition. It was unfortunate that this study did not involve women, because such results are important for understanding urge incontinence, which occurs more frequently in women than in men. Therefore, a similar study was done in 18 right-handed women, who were scanned during the following four conditions: (i) 15 min prior to micturition (urine withholding); (ii) during micturition; (iii) 15 min after micturition; and (iv) 30 min after micturition. Of the 18 volunteers, 10 were able to micturate during scanning and eight were not, despite trying vigorously. Micturition appeared to be associated with significantly increased blood flow in the right dorsal pontine tegmentum and the right inferior frontal gyrus. Decreased blood flow was found in the right anterior cingulate gyrus during urine withholding. The eight volunteers who were not able to micturate during scanning did not show significantly increased regional cerebral blood flow in the right dorsal, but did so in the right ventral pontine tegmentum. In the cat this region controls the motor neurons of the pelvic floor. In the same unsuccessful micturition group, increased blood flow was also found in the right inferior frontal gyrus. In all 18 volunteers, decreased blood flow in the right anterior cingulate gyrus was found during the period when they had to withhold their urine prior to the micturition condition. The results suggest that in women and in men the same specific nuclei exist in the pontine tegmentum responsible for the control of micturition. The results also indicate that the cortical and pontine micturition sites are more active on the right than on the left side.

Adult↗

A PET study on cortical and subcortical control of pelvic floor musculature in women.

The pelvic floor musculature plays an important role in behaviors such as defecation, micturition, mating behavior, and vomiting. A recent positron emission tomography (PET) study revealed that structures belonging to the emotional motor system are involved in the control of the pelvic floor during micturition. However, there also exist brain structures involved in the voluntary motor control of the pelvic floor, and the present PET study was designed to identify these structures. Six adult female volunteers were scanned with the bolus injection of H2(15)O during the following four conditions: (1) rest, (2) repetitive pelvic floor straining, (3) sustained pelvic floor straining, and (4) sustained abdominal straining. The results revealed that the superomedial precentral gyrus, the most medial portion of the motor cortex, is activated during pelvic floor contraction and the superolateral precentral gyrus during contraction of the abdominal musculature. In these conditions, significant activations were also found in the cerebellum, supplementary motor cortex, and thalamus. The right anterior cingulate gyrus was activated during sustained pelvic floor straining. No activations were found in subcortical structures belonging to the emotional motor system. The results are discussed in light of the existing literature on human control of the pelvic floor and micturition.

Abdominal Muscles↗

The pontine micturition center projects to sacral cord GABA immunoreactive neurons in the cat.

Stimulation of the pontine micturition center (PMC) results in micturition, i.e. an immediate relaxation of the bladder sphincter and a contraction of the detrusor muscle of the bladder. Earlier studies have shown that the bladder contraction is brought about by a direct excitatory pathway from the PMC to the parasympathetic bladder motoneurons in the sacral cord. How the PMC produces the inhibition of the bladder sphincter is not known. The present study in two adult male cats demonstrates at the ultrastructural level a direct pathway from the PMC to the dorsal gray commissure of the sacral cord. More than half (55%) of these terminals made contact with gamma amino butyric acid (GABA) immunoreactive neurons or somata, the others with non-GABA immunoreactive profiles. The PMC terminals contained many round vesicles, some dense cored vesicles and exclusively asymmetric synaptic clefts, which correspond with an excitatory pathway. A concept is put forward in which this pathway produces the relaxation of the bladder sphincter during micturition.

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Ultrastructural evidence for a direct pathway from the pontine micturition center to the parasympathetic preganglionic motoneurons of the bladder of the cat.

Light microscopy tracing studies have provided evidence that the pontine micturition center (PMC) projects to the area of the intermediolateral cell column of the sacral spinal cord. Although this region contains parasympathetic preganglionic motoneurons of the bladder and colon, it also contains many local interneurons and neurons projecting to supraspinal levels. The present study demonstrates that neurons in the PMC indeed project to preganglionic bladder motoneurons. Wheat germ agglutinin horseradish peroxidase was injected in the PMC and cholera toxin B subunit was injected in the bladder wall. Many anterogradely labeled fibers from the PMC were found to terminate on somata and dendrites of the retrogradely labeled preganglionic bladder motoneurons. The terminals were filled with many round vesicles and possessed an asymmetric synaptic cleft, suggesting an excitatory function.

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A PET study on brain control of micturition in humans.

Although the brain plays a crucial role in the control of micturition, little is known about the structures involved. Identification of these areas is important, because their dysfunction is though to cause urge incontinence, a major problem in the elderly. In the cat, three areas in the brainstem and diencephalon are specifically implicated in the control of micturition: the dorsomedial pontine tegmentum, the periaqueductal grey, and the preoptic area of the hypothalamus. PET scans were used to test whether these areas are also involved in human micturition. Seventeen right-handed male volunteers were scanned during the following four conditions: (i) 15 min prior to micturition during urine withholding: (ii) during micturition; (iii) 15 min after micturition; (iv) 30 min after micturition. Ten of the 17 volunteers were able to micturate during scanning. micuturition was associated with increased blood flow in the right dorsomedial pontine tegmentum, the periaqueductal grey, the hypothalamus and the right inferior frontal gyrus. Decreased blood flow was found in the right anterior cingulate gyrus when urine was withheld. The other seven volunteers were not able to micturate during scanning, although they had a full bladder and tried vigorously to do so. In this group, during these unsuccessful attempts to micturate, increased blood flow was found in the right ventral pontine tegmentum, which corresponds with the hypothesis, formulated from results in cats, that this area controls the motor neurons of the pelvic floor. Increased blood flow was also found in the right inferior frontal gyrus during unsuccessful attempts at micturition, and decreased blood flow in the right anterior cingulate gyrus was found during the withholding of urine. The results suggest that, as that of the cat, the human brainstem contains specific nuclei responsible for the control of micturition, and that the cortical and pontine micturition sites are predominantly on the right side.

Adult↗

Distinct cell groups in the lumbosacral cord of the cat project to different areas in the periaqueductal gray.

The periaqueductal gray (PAG) is involved in aggressive and defensive behavior, micturition, and lordosis. Especially for the latter two functions, PAG afferents from the lumbosacral cord are of vital importance because, in addition to information regarding homeostasis and thermoregulation, they convey information from the pelvic viscera and sex organs. In the present retro- and antero-grade tracing study, the projection patterns of different lumbosacral cell groups in the PAG were determined. In the retrograde study, wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) injections were made in the PAG and/or adjacent tegmentum, and in the anterograde study, WGA-HRP was injected in different lumbosacral segments. The results revealed that lumbosacral-PAG neurons could be divided into three groups. The first and largest group was present in lumbar 7-sacral 3 segments (L7-S3) and consisted of small, oval, and fusiform neurons. It extended from the dorsolateral part of lamina I in L7, along the lateral part of the dorsal horn in S1, and into lamina V of S2. In the lateral part of S2, some of its neurons formed clusters with intervals of +/- 230 microns. The location of the first group overlapped extensively with the termination area of pelvic and pudendal afferents. The main midbrain target of the first group was the medial part of the lateral PAG. The second group consisted of small to large multipolar neurons in laminae VIII and medial VII of caudal L6, L7, and rostral S1. This group projected strongly to a distinct region in the lateral part of the lateral PAG and the laterally adjacent tegmentum. About 10% of the labeled neurons did not fit in the two groups. They were evenly distributed throughout lumbar 4-coccygeal 3 segments (L4-Co3) and consisted of large multipolar lamina V neurons and small lamina I neurons that projected diffusely to the lateral and dorsal PAG. The large lamina V neurons also targeted the laterally adjacent tegmentum. The possible involvement of the lumbosacral-PAG projections in micturition, lordosis, and defensive and aggressive behavior is discussed.

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Location of external anal sphincter motoneurons in the sacral cord of the female domestic pig.

The location of the striated external anal sphincter motoneurons in the spinal cord was investigated in 12, between 3 and 4 months old, female domestic pigs using the retrograde tracer horseradish peroxidase (HRP). Their motoneuronal cell bodies were found in the spinal segments S1-S3, and were not located in the ventral horn, but dorsolateral to the central canal. This location within the spinal gray matter strongly differs from the location of the external and sphincter motoneurons in rat, cat, dog, monkey and humans, but is similar to that in the Mongolian gerbil. The possible relevance of this 'aberrant' location is discussed.

Anal Canal↗

Ultrastructural evidence for a paucity of projections from the lumbosacral cord to the pontine micturition center or M-region in the cat: a new concept for the organization of the micturition reflex with the periaqueductal gray as central relay.

Information concerning the rate of bladder filling is determined by receptors in the bladder wall and conveyed via afferent fibers in the pelvic nerve to sensory neurons in the lumbosacral cord. It was assumed that this information is relayed from the lumbosacral cord to a medial cell group in the dorsolateral pontine tegmentum, called the M-region, the pontine micturition center, or Barrington's nucleus. The M-region, in turn, projects via long descending pathways to the sacral parasympathetic motoneurons. In the present electron microscopic study, it was investigated in cats whether monosynaptic projections from lumbosacral neurons to the M-region indeed exist. Wheat-germ agglutinin-horseradish peroxidase injections were made into the lumbosacral cord. Many retrogradely labeled dendrites and somata were found in the M-region, but no labeled terminals were found on retrogradely labeled dendrites or somata. Only a small number of anterogradely labeled terminals, which were filled with mainly round vesicles, contacted unlabeled dendrites in the M-region. In contrast, many more anterogradely labeled terminals, which were filled with mainly round and, to a limited extent, dense core vesicles and with asymmetrical synapses, were found on dendrites in the lateral part of the periaqueductal gray (PAG). Previously (Blok and Holstege [1994] Neurosci. Lett. 166:93-96), it was demonstrated that the lateral part of the PAG contains neurons projecting to the M-region. A concept for the central organization of the micturition reflex is presented in which ascending projections from the lumbosacral cord convey information on bladder filling to the PAG.(ABSTRACT TRUNCATED AT 250 WORDS)

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Direct projections from the periaqueductal gray to the pontine micturition center (M-region). An anterograde and retrograde tracing study in the cat.

Micturition is a spino-bulbo-spinal reflex. The bulbospinal part of this reflex is formed by the projections from the M-region, also called the pontine micturition center or Barrington's nucleus, to the preganglionic parasympathetic motoneurons in the sacral cord innervating the bladder. In respect to the spino-bulbar part of the micturition reflex, our group recently showed that the sacral cord projections to the brainstem terminate mainly in the periaqueductal gray (PAG). In this study it was investigated whether the PAG might serve as a link between the sacral cord and the M-region, by examining the possible connections using the tracers wheat germ-agglutin horseradish peroxidase and tritiated leucine. The results demonstrate that a specific circumscribed rostrocaudally oriented cell group within the ventrolateral PAG and parts of the dorsomedial PAG project specifically to the M-region. A concept is put forward in which specific parts of the PAG are involved in the control of micturition and that information concerning bladder filling is conveyed via the PAG to the M-region.

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Descending pathways to the cutaneous trunci muscle motoneuronal cell group in the cat.

1. The cutaneus trunci muscle (CTM) is a thin broad sheet of skeletal muscle just beneath the skin. It does not contain muscle spindles and receives its afferents from the overlying skin. Contraction of the muscle can easily be triggered by pinching the skin or, in the cat, by gentle displacement of the fur (CTM reflex). The afferent information of this reflex is conveyed via the cutaneous nerves, which are segmentally organized. In the cat, the CTM motoneurons are located in a circumscribed cell group in the ventrolateral part of the ventral horn of the C8 and T1 spinal segments. The CTM motor nucleus corresponds with "nucleus X" of Giovanelli Barilari and Kuypers and with "ventral motor nucleus" of Matsushita and Ueyama. 2. Relatively long ascending propriospinal pathways, originating in the thoracolumbar cord, exist between the cutaneous afferents and the CTM motor nucleus. Such pathways have been described physiologically, as well as anatomically. Our results, based on anterograde autoradiographic experiments with [3H]leucine injections in the C1, C2, C6, and C8 segments, suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do not exist, although these propriospinal projections are very strong to all other motoneuronal cell groups surrounding the CTM motor nucleus. 3. The present results also demonstrate specific supraspinal projections to the CTM motor nucleus originating in 1) the contralateral nucleus retroambiguous (NRA) and 2) the ipsilateral dorsolateral pontine tegmentum. These projections suggest that the CTM motor nucleus is not only involved in spinal reflexes, but also in other functions such as abdominal straining.(ABSTRACT TRUNCATED AT 250 WORDS)

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