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G Holstege

Publications and source records attributed to G Holstege.

At least 55 records · Page 3Linked to original sources

Motoneuronal location of the external urethral and anal sphincters: a single and double labeling study in the male and female golden hamster.

The location of external urethral (EUS) and anal sphincter (EAS) motoneurons was investigated in the golden hamster using the retrograde tracers horseradish peroxidase and cholera toxin B-subunit. Single and double labeling studies revealed that the motoneurons of the EUS and EAS were present in the same nucleus (nucleus of Onuf) ventrolaterally in the ventral horn of the caudal first sacral segment and throughout the second sacral segment. Within Onuf's nucleus the EAS motoneurons were located dorsomedial to the EUS motoneurons, which were located at the border of the gray and white matter. This location is similar to that in cat, dog, monkey and man, but differs from that in rat, Mongolian gerbil and domestic pig.

Anal Canal↗

Evidence for monosynaptic projections from the nucleus retroambiguus to hindlimb motoneurons in the cat.

The nucleus retroambiguus (NRA) is a group of premotor neurons at the transition between brainstem and spinal cord. It projects to certain motoneuronal cell groups, among which is a distinct set of motoneurons in the lumbar enlargement innervating muscles including iliopsoas, adductor longus, and hamstrings. To find out whether these NRA-motoneuronal projections are monosynaptic, injections of wheat germ-agglutinin horseradish peroxidase (WGA-HRP) into the NRA were combined with injections of cholera toxin subunit b (CTb) into the hamstring muscles. Electron microscopical examination revealed that the NRA terminal profiles make monosynaptic contacts with dendrites of motoneurons innervating these muscles. The NRA terminal profiles formed asymmetrical synapses, and contained spherical and a few dense core vesicles. These findings provide evidence of monosynaptic NRA-hindlimb motoneuronal projections which are likely to be excitatory.

Animals↗

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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Estrogen induces axonal outgrowth in the nucleus retroambiguus-lumbosacral motoneuronal pathway in the adult female cat.

In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VGJM, Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a compact group of interneurons located laterally in the caudal medulla oblongata. Its projection to lumbosacral motoneurons is thought to represent the final common pathway for male mounting and for female receptive or lordosis behavior. However, females only display lordosis behavior. However, females only display lordosis behavior when they are in estrus, which suggests that the NRA-lumbosacral pathway is only active during estrus. This raised the question of whether estrogen affects this pathway. The effect of estrogen on the NRA-lumbosacral projection was studied light microscopically, using wheat-germ agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway served as control. The density of labeled NRA fibers in their target hindlimb motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous cats. Such differences were not found in the rubrospinal pathway. For electron microscopical study, the NRA projection to the semi-membranosus motoneuronal cell group was selected. In this cell group, an almost ninefold increase of labeled profiles was found in estrous versus nonestrous cats. Moreover, the semimembranous motoneuronal cell group contained labeled growth cones in estrous, but not in nonestrous, cats. The present study is the first to show that estrogen induces axonal outgrowth of a precisely identified pathway in the adult mammalian central nervous system. The possible mechanisms underlying this outgrowth are discussed.

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Evidence for a periaqueductal gray-nucleus retroambiguus-spinal cord pathway in the rat.

The nucleus retroambiguus in the cat has been shown to receive strong projections from the periaqueductal gray and to send fibres to distinct motoneuronal cell groups in brainstem and spinal cord. The nucleus retroambiguus plays a role in the production of vocalization and possibly copulatory (lordosis and mounting) behaviour. The question arises of whether a periaqueductal gray nucleus retroambiguus-spinal cord projection also exists in the rat. In the present study, using the retrograde wheatgerm agglutinin-horseradish peroxidase tracing technique, the nucleus retroambiguus was defined as the area in the caudal medulla oblongata (1.0-2.0 mm caudal to the obex) which sends its fibres mainly through the contralateral spinal cord. Further retrograde tracing experiments demonstrated that a relatively large number of neurons in the lateral and ventral periaqueductal gray and immediately adjacent tegmentum projects to the caudal medullary lateral tegmentum. Anterograde wheatgerm agglutinin-horseradish peroxidase tracing studies finally showed that neurons in the lateral periaqueductal gray and immediately adjoining tegmentum project specifically to the nucleus retroambiguus and not to the lateral tegmentum in general, which seems to be the case for the neurons in the ventral periaqueductal gray. The results indicate that in the rat a periaqueductal gray nucleus retroambiguus spinal cord projection also exists, which may be of crucial importance for the study of the anatomical and physiological framework of respiration, vocalization, and female and male reproductive behaviour in this animal.

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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↗

The late blink reflex response abnormality due to lesion of the lateral tegmental field.

We report on a blink reflex abnormality observed in two patients, which provides additional information on the central pathways mediating this reflex. Autopsy was performed in one patient and MRI in the other. In the first patient there was a small lesion at the dorsal middle third of the lateral tegmental field and in the second patient at the level of the dorsal lower third of the medulla oblongata. In both patients the common finding was the absence of the late response (R2) ipsilateral to the side of the lesion, while the R2 response on the unaffected side was normal regardless of the side of the supraorbital nerve stimulation. The R1 responses were normal. This type of blink reflex abnormality has not been reported before and is referred to by us as 'tegmental type' of R2 abnormality. The results led to the conclusions that: (i) the crossed and uncrossed ascending trigeminofacial connections are mediated through the lateral tegmental field; (ii) the uncrossed trigeminofacial connection originates at the level of at least the lower medulla oblongata; (iii) the contralateral R2 response is established by way of an ascending pathway, which crosses the midline at the level of at least the lower third of the medulla oblongata.

Afferent Pathways↗

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.

Animals↗

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↗

Pontine and medullary projections to the nucleus retroambiguus: a wheat germ agglutinin-horseradish peroxidase and autoradiographic tracing study in the cat.

The nucleus retroambiguus (NRA) in the caudal medulla oblongata plays a role in expiration, vocalization, vomiting, and possibly lordosis. The present study tried to determine which structures, in turn, control the NRA. One cell group is the periaqueductal gray (PAG), which is considered to be the final integrator of defensive and aggressive behaviors, micturition, vocalization, and lordosis. Structures rostral to the PAG seem to bypass the NRA. With respect to the existence of cell groups caudal to the PAG projecting to the NRA, the situation is less clear. Therefore, in five adult female cats, injections of wheat germ agglutinin-horseradish peroxidase were centered on the NRA, and the resulting retrogradely labeled neurons were plotted. In the areas containing retrogradely labeled cells, the anterograde autoradiographic tracer [3H]-leucine was injected in 66 cats. The combined results demonstrated that NRA afferents not only originate from the PAG but also from specific cell groups in the pontine and medullary lateral tegmental field, i.e., the ventrolateral parabrachial nucleus, the nucleus Kölliker-Fuse, the retrotrapezoid nucleus, and the ventrolateral part of the medulla caudal to the facial nucleus including the Bötzinger and pre-Bötzinger complex and the periambigual region. Afferents also originate from the solitary nucleus and two cell groups in the ventral part of the medullary medial tegmental field, one at the level of facial nucleus and one just rostral to the hypoglossal nucleus. It can be concluded that many respiratory-related cell groups have direct access to the NRA. The cell groups in the medial tegmental field, which have not yet been found to play an important role in respiration, might serve as relay for certain limbic system cell groups to reach the NRA in the context of specific emotional behavior.

Afferent Pathways↗

Dorsal border periaqueductal gray neurons project to the area directly adjacent to the central canal ependyma of the C4-T8 spinal cord in the cat.

In a previous study horseradish peroxidase (HRP) injections in the upper thoracic and cervical spinal cord revealed some faintly labeled small neurons at the dorsal border of the periaqueductal gray (PAG). The present light microscopic and electronmicroscopic tracing study describes the precise location of these dorsal border PAG-spinal neurons and their terminal organization. Wheat germ agglutinin-conjugated HRP (WGA-HRP) injections into cervical and upper thoracic spinal segments resulted in several hundreds of small retrogradely labeled neurons at the dorsal border of the ipsilateral caudal PAG. These neurons were not found after injections in more caudal segments. WGA-HRP injections in the dorsal border PAG region surprisingly resulted in anterogradely labeled fibers terminating in the area dorsally and laterally adjoining the central canal ependyma of the C4-T8 spinal cord. No anterogradely labeled fibers were found more caudal in the spinal cord. The labeled fibers found in the upper cervical cord were not located in the area immediately adjoining the ependymal layer of the central canal, but in the lateral part of laminae VI, VII and VIII and in area X bilaterally. Electronmicroscopic results of one case show that the dorsal border PAG-spinal neurons terminate in the neuropil of the subependymal area and in the vicinity of the basal membranes of capillaries located laterally to the central canal. The terminal profiles contain electron-lucent and densecored vesicles, suggesting a heterogeneity of possible transmitters. A striking observation was the lack of synaptic contacts, suggesting nonsynaptic release from the profiles. The function of the dorsal border PAG-spinal projection is unknown, but considering the termination pattern of the dorsal border PAG neurons on the capillaries the intriguing similarity between this projection system and the hypothalamohypophysial system is discussed.

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Blepharospasm in association with a lower pontine lesion.

A patient with neurofibromatosis type I and breast carcinoma developed a bilateral but asymmetric blepharospasm and paresis of the left abducens muscle over a 2-week course. MRI disclosed a small lesion in the left dorsomedial lower pontine region. Electrodiagnostic investigations revealed bilateral R1 responses after stimulation of the left supraorbital nerve and enhancement of R1 and R2 recovery curves. We concluded that lesions in the lower pontine tegmentum may cause blepharospasm.

Blepharospasm↗

Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis.

The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made to localize and quantify the retrogradely labeled neurons in the caudal medullary lateral tegmentum. These injections were combined with spinal hemisections to distinguish between neurons having ipsi-or contralaterally descending axons. The NRA-lumbosacral fibers descend almost exclusively contralaterally, but neurons in areas surrounding the NRA project mainly ipsilaterally. In an anterograde tracing study, injections of WGA-HRP or tritiated leucine were made in the region of the NRA to determine the NRA targets in the lumbosarcral cord. Hemisections in C2 made it possible to distinguish between NRA projections and projections from neurons in the adjoining lateral tegmentum. The results show delicate NRA projections to distinct lumbosacral motoneuronal cell groups innervating specific hindlimb muscles (iliopsoas, adductors, and hamstrings) as well as axial muscles (medial longissimus and proximal tail muscles). The projection is bilateral, with a contralateral predominance. Ipsilaterally terminating fibers are derived from NRA neurons whose axons cross the midline at the level of the obex, descend through the contralateral spinal white matter, and recross at the level of termination. A conceptual description is presented in which the periaqueductal gray-NRA-lumbosacral projections form the final common pathway for lordosis in the cat.

Animals↗

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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