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Biomedical subjects

G Holstege

Publications and source records attributed to G Holstege.

At least 73 records · Page 4Linked to original sources

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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The periaqueductal gray in the cat projects to lamina VIII and the medial part of lamina VII throughout the length of the spinal cord.

The periaqueductal gray (PAG) plays an important role in analgesia as well as in motor activities, such as vocalization, cardiovascular changes, and movements of the neck, back, and hind limbs. Although the anatomical pathways for vocalization and cardiovascular control are rather well understood, this is not the case for the pathways controlling the neck, back, and hind limb movements. This led us to study the direct projections from the PAG to the spinal cord in the cat. In a retrograde tracing study horseradish peroxidase (HRP) was injected into different spinal levels, which resulted in large HRP-labeled neurons in the lateral and ventrolateral PAG and the adjacent mesencephalic tegmentum. Even after an injection in the S2 spinal segment a few of these large neurons were found in the PAG. Wheat germ agglutinin-conjugated HRP injections in the ventrolateral and lateral PAG resulted in anterogradely labeled fibers descending through the ventromedial, ventral, and lateral funiculi. These fibers terminated in lamina VIII and the medial part of lamina VII of the caudal cervical, thoracic, lumbar, and sacral spinal cord. Interneurons in these laminae have been demonstrated to project to axial and proximal muscle motoneurons. The strongest PAG-spinal projections were to the upper cervical cord, where the fibers terminated in the lateral parts of the intermediate zone (laminae V, VII, and the dorsal part of lamina VIII). These laminae contain the premotor interneurons of the neck muscles. This distribution pattern suggests that the PAG-spinal pathway is involved in the control of neck and back movements. Comparing the location of the PAG-spinal neurons with the results of stimulation experiments leads to the supposition that the PAG-spinal neurons play a role in the control of the axial musculature during threat display.

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A new subdivision of the rat midbrain periaqueductal gray based on its myeloarchitecture.

A new subdivision of the periaqueductal gray (PAG) based on its myelin content is described. Using a methacrylate-resin embedding technique for high resolution light microscopy, a myeloarchitectonic map of the normal rat PAG was made. Six main columns were distinguished. Column I is the central thin subependymal layer, in which myelinated axons are virtually absent. This layer is surrounded by column II with many rostrocaudally oriented fibers. Lateral and dorsolateral to column II lies column III, which contains rostrocaudally as well as tangentially oriented fibers. Column III is divided into a ventral and a dorsal part by column IV. This column is located in the dorsolateral part of the PAG and contains very few, mostly tangentially oriented fibers. Column V is located ventrally and contains a mixture of rostrocaudally and tangentially oriented fibers. Column VI is only present in the most caudal part of the PAG and contains mainly tangential fibers.

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Dorsal mesencephalic projections to pons, medulla, and spinal cord in the cat: limbic and non-limbic components.

The vertebrate dorsal mesencephalon consists of the superior colliculus, the dorsal portion of the periaqueductal gray, and the mesencephalic trigeminal neurons in between. These structures, via their descending pathways, take part in various behavioral responses to environmental stimuli. This study was undertaken to compare the origins and trajectories of these pathways in the cat. Injections of horseradish peroxidase into the cervical spinal cord and upper medullary medial tegmentum retrogradely labeled cells mainly in the contralateral intermediate and deep superior colliculus, and in the ipsilateral dorsal and lateral periaqueductal gray and adjacent tegmentum. Only injections in the medullary lateral tegmental field labeled mesencephalic trigeminal neurons ipsilaterally. Autoradiographic tracing results, based on injections across the dorsal mesencephalon, revealed three efferent fiberstreams. A massive first fiberstream (limbic pathway), consisting of thin fibers, descended ipsilaterally from the dorsal and lateral periaqueductal gray and adjacent superior colliculus through the mesencephalic and pontine lateral tegmentum, terminating in these areas as well as in the ventral third of the caudal pontine and medullary medial tegmentum. A few fibers from the dorsal periaqueductal gray matter (PAG) were distributed bilaterally to the dorsal vagal, solitary, and retroambiguus nuclei. The second fiberstream (the predorsal bundle) descended contralaterally from the superior colliculus (SC) and consisted of both thick and thin labeled fibers. The thin fibers terminated bilaterally in the dorsomedial nucleus reticularis tegmenti pontis and the medial half of the caudal medial accessory inferior olive. The thick fibers targeted the contralateral dorsal two thirds of the caudal pontine and medullary medial tegmental fields, and the facial, abducens, lateral reticular, subtrigeminal, and prepositus hypoglossi nuclei. A few fibers recrossed the midline to terminate in the ipsilateral medial tegmentum. Caudal to the obex, fibers terminated laterally in the tegmentum and upper cervical intermediate zone. From the lateral SC, fibers terminated bilaterally in the lateral tegmental fields of the pons and medulla and lateral facial subnuclei. The third fiberstream (mesencephalic trigeminal or Probst tract) terminated in the supratrigeminal and motor trigeminal nuclei, and laterally in the tegmentum and upper cervical intermediate zone. In summary, neurons in the PAG and in the deep layers of the SC give rise to a massive ipsilateral descending pathway, in which a medial-to-lateral organization exists. A similar topographical pattern occurs in the crossed SC projections. The possibility that these completely different descending systems cooperate in producing specific defensive behaviors is discussed.

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The emotional motor system.

A large number of new descending motor pathways to caudal brainstem and spinal cord have been recognized recently. Nevertheless all the new pathways seem to belong to one of three motor systems in the central nervous system (CNS). This survey gives an overview of the pathways belonging to the so-called emotional motor system or the third motor system as defined by Holstege. The similarities and differences with the core, median and lateral paracore areas of the CNS as defined by Nieuwenhuys are discussed.

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Anatomical study of the final common pathway for vocalization in the cat.

Vocalization, the nonverbal production of sound, can be elicited in many vertebrates by stimulation in several regions of the limbic system but most easily in the caudal periaqueductal gray (PAG). This study shows that a specific cell group in the lateral part of the caudal PAG and in the tegmentum just lateral to it projects bilaterally to the nucleus retroambiguus (NRA) in the caudal medulla oblongata. Similar but much weaker projections are derived from the dorsal PAG. Neurons in the NRA in turn project via a contralateral pathway through the ventral funiculus of the spinal cord to motoneuronal cell groups, innervating intercostal and abdominal muscles. These projections are stronger on the contralateral side, although at lower thoracic and upper lumbar levels, many fibers recross to terminate in the ipsilateral motoneuronal cell groups. In the brainstem NRA neurons project to the motoneuronal cell groups innervating mouth-opening and perioral muscles as well as to motoneurons innervating the pharynx, soft palate, and tongue, and probably to the larynx. All these muscles are active in vocalization. The present anatomical results, combined with the physiological results of others, indicate that the projections from PAG via NRA to vocalization motoneurons form the final common pathway in vocalization. The role of this pathway in the total framework of emotional behavior is discussed.

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Projections from the rostral mesencephalic reticular formation to the spinal cord. An HRP and autoradiographical tracing study in the cat.

Eye and head movements are strongly interconnected, because they both play an important role in accurately determining the direction of the visual field. The rostral brainstem includes two areas which contain neurons that participate in the control of both movement and position of the head and eyes. These regions are the caudal third of Field H of Forel, including the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal with adjacent reticular formation (INC-RF). Lesions in the caudal Field H of Forel in monkey and man result in vertical gaze paralysis. Head tilt to the opposite side and inability to maintain vertical eye position follow lesions in the INC-RF in cat and monkey. Projections from these areas to extraocular motoneurons has previously been observed. We reported a study of the location of neurons in Field H of Forel and INC-RF that project to spinal cord in cat. The distribution of these fiber projections to the spinal cord are described. The results indicate that: 1. Unlike the neurons projecting to the extra-ocular muscle motoneurons, the major portion of the spinally projecting neurons are not located in the riMLF or INC proper but in adjacent areas, i.e. the ventral and lateral parts of the caudal third of the Field H of Forel and in the INC-RF. A few neurons were also found in the nucleus of the posterior commissure and ventrally adjoining reticular formation. 2. Neurons in caudal Field H of Forel project, via the ventral part of the ventral funiculus, to the lateral part of the upper cervical ventral horn. This area includes the laterally located motoneuronal cell groups, innervating cleidomastoid, clavotrapezius and splenius motoneurons. At lower cervical levels labeled fibers are distributed to the medial part of the ventral horn. Projections from the caudal Field H of Forel to thoracic or more caudal spinal levels are sparse. 3. Neurons in the INC-RF, together with a few neurons in the area of the nucleus of the posterior commissure, project bilaterally to the medial part of the upper cervical ventral horn, via the dorsal part of the ventral funiculus. This area includes motoneurons innervating prevertebral flexor muscles and some of the motoneurons of the biventer cervicis and complexus muscles. Further caudally, labeled fibers are distributed to the medial part of the ventral horn (laminae VIII and adjoining VII) similar to the projections of Field H of Forel. A few INC-RF projections were observed to low thoracic and lumbosacral levels.(ABSTRACT TRUNCATED AT 400 WORDS)

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Afferent and efferent connections of the cholinoceptive medial pontine reticular formation (region of the ventral tegmental nucleus) in the cat.

Following minor concussive brain injury when there is an otherwise general suppression of CNS activity, the ventral tegmental nucleus of Gudden (VTN) demonstrates increased functional activity (32). Electrical or pharmacological activation of a cholinoceptive region in this same general area of the medial pontine tegmentum contributes to certain components of reversible traumatic unconsciousness, including postural atonia (31, 32, 45). Therefore, in an effort to examine the neuroanatomical basis of the behavioral suppression associated with a reversible traumatic unconsciousness, the afferent and efferent connections of the VTN and putative cholinoceptive medial pontine reticular formation (cmPRF) were studied in the cat using the retrograde horseradish peroxidase (HRP), HRP/choline acetyltransferase (ChAT) double-labeling immunohistochemistry, and anterograde HRP and autoradiographic techniques. Based upon retrograde HRP labeling, the principal afferents to the VTN region of the cmPRF originated from the medial and lateral mammillary nuclei, and lateral habenular nucleus, and to a lesser extent from the interpeduncular nucleus, lateral hypothalamus, dorsal tegmental nucleus, superior central nucleus, and contralateral nucleus reticularis pontis caudalis. Other afferents, which were thought to have been labeled through spread of HRP into the medial longitudinal fasciculus (MLF), adjacent paramedian pontine reticular formation, or uptake by transected fibers descending to the inferior olive, included the nucleus of Darkschewitsch, interstitial nucleus of Cajal, zona incerta, prerubral fields of Forel, deep superior colliculus, nucleus of the posterior commissure, nucleus cuneiformis, ventral periaqueductal gray, vestibular complex, perihypoglossal complex, and deep cerebellar nuclei. In HRP/ChAT double labeling studies, only a very small number of cholinergic VTN afferent neurons were found in the medial parabrachial region of the dorsolateral pontine tegmentum, although the pedunculopontine and laterodorsal tegmental nuclei contained numerous single-labeled ChAT-positive cells. Anterograde HRP and autoradiographic findings demonstrated that the VTN gave rise almost exclusively to ascending projections, which largely followed the course of the mammillary peduncle (16,21) and medial forebrain bundle, or the tegmentopeduncular tract (4). The majority of fibers ascended to terminate in the medial and lateral mammillary nuclei, interpeduncular complex (especially paramedian subnucleus), ventral tegmental area, lateral hypothalamus, and the medial septum in the basal forebrain. Labeling that joined the mammillothalamic tract to terminate in the anterior nuclear complex of the thalamus was thought to occur transneuronally. Some projections were also observed to nucleus reticularis pontis oralis and caudalis, superior central nucleus, and dorsal tegmental nucleus adjacent to the VTN...

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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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Anatomical evidence for red nucleus projections to motoneuronal cell groups in the spinal cord of the monkey.

In 4 rhesus monkeys wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections were made in the mesencephalic tegmentum. In 3 cases with injections involving the red nucleus (RN), rubrospinal fibers descended mainly contralaterally to terminate in laminae V, VI and dorsal VII of the spinal cord and in the lateral motoneuronal cell groups at the level of the cervical and lumbosacral enlargements. In all 4 cases the area of the interstitial nucleus of Cajal (INC) was injected, which resulted in labeled interstitiospinal fibers in the medial part of the ipsilateral ventral funiculus of the spinal cord. The results indicate that there is no major qualitative difference between the mesencephalic (RN and INC) and motor cortical projections to the spinal cord.

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Ultrastructural evidence for direct monosynaptic rubrospinal connections to motoneurons in Macaca mulatta.

The magnocellularis division of the red nucleus of the Macaca mulatta, a midbrain structure involved in processing motor information, is known by light microscopic analysis to project, via the rubrospinal tract, to the contralateral intermediate horn of the spinal cord. Physiological studies, however, provide additional evidence for direct monosynaptic connections to motoneurons subserving distal musculature. This electron microscopic study demonstrates, by analyzing the anterograde transport of 5% wheatgerm agglutinin-horseradish peroxidase injected into the red nucleus, the presence of labeled terminals synapsing upon somata and proximal dendrites of motoneurons in the lateral portion of the ventral horn of the cervical enlargement of the spinal cord. We conclude that this anatomical evidence confirms the presence of direct monosynaptic connections to spinal motoneurons in the primate.

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Anatomical evidence for a strong ventral parabrachial projection to nucleus raphe magnus and adjacent tegmental field.

Injections with [3H]leucine in the ventral parabrachial nuclei and nucleus Kölliker-Fuse of the cat revealed strong projections to the nucleus raphe magnus (NRM) and adjacent tegmentum, while similar injections in the adjacent nucleus subcoeruleus produced diffuse projections to large parts of the tegmentum, but not specifically to the NRM. Horseradish peroxidase (HRP) injections in the area of the NRM and adjacent tegmentum demonstrated many labeled neurons in the ventral parabrachial nuclei, nucleus Kölliker-Fuse and nucleus subcoeruleus. These results suggest that the inhibition of nociception induced by stimulation in the ventral parabrachial nuclei may be based on the projections of this area to NRM and adjacent tegmentum.

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Brainstem-spinal cord projections in the cat, related to control of head and axial movements.

Unlike the other chapters, this is mainly an experimental study. It describes the location of all pathways descending from the brainstem to the spinal cord in cat: and for the first time correlates the termination fields arising from specific brainstem areas with the inter- and motoneuron pools of neck, axial and distal limb musculature, throughout the whole spinal cord. The findings are related to previous studies, as well as to functional aspects of the oculomotor system.

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Some anatomical observations on the projections from the hypothalamus to brainstem and spinal cord: an HRP and autoradiographic tracing study in the cat.

The hypothalamus is closely involved in a wide variety of behavioral, autonomic, visceral, and endocrine functions. To find out which descending pathways are involved in these functions, we investigated them by horseradish peroxidase (HRP) and autoradiographic tracing techniques. HRP injections at various levels of the spinal cord resulted in a nearly uniform distribution of HRP-labeled neurons in most areas of the hypothalamus except for the anterior part. After HRP injections in the raphe magnus (NRM) and adjoining tegmentum the distribution of labeled neurons was again uniform, but many were found in the anterior hypothalamus as well. Injections of 3H-leucine in the hypothalamus demonstrated that: The anterior hypothalamic area sent many fibers through the medial forebrain bundle (MFB) to terminate in the ventral tegmental area of Tsai (VTA), the rostral raphe nuclei, the nucleus Edinger-Westphal, the dorsal part of the substantia nigra, the periaqueductal gray (PAG), and the interpeduncular nuclei. Further caudally a lateral fiber stream (mainly derived from the lateral parts of the anterior hypothalamic area) distributed fibers to the parabrachial nuclei, nucleus subcoeruleus, locus coeruleus, the micturition-coordinating region, the caudal brainstem lateral tegmentum, and the solitary and dorsal vagal nucleus. Furthermore, a medial fiber stream (mainly derived from the medial parts of the anterior hypothalamic area) distributed fibers to the superior central and dorsal raphe nucleus and to the NRM, nucleus raphe pallidus (NRP), and adjoining tegmentum. The medial and posterior hypothalamic area including the paraventricular hypothalamic nucleus (PVN) sent fibers to approximately the same mesencephalic structures as the anterior hypothalamic area. Further caudally two different fiber bundles were observed. A medial stream distributed labeled fibers to the NRM, rostral NRP, the upper thoracic intermediolateral cell group, and spinal lamina X. A second and well-defined fiber stream, probably derived from the PVN, distributed many fibers to specific parts of the lateral tegmental field, to the solitary and dorsal vagal nuclei, and, in the spinal cord, to lamina I and X, to the thoracolumbar and sacral intermediolateral cell column, and to the nucleus of Onuf. The lateral hypothalamic area sent many labeled fibers to the lateral part of the brainstem and many terminated in the caudal brainstem lateral tegmentum, including the parabrachial nuclei, locus coeruleus, nucleus subcoeruleus, and the solitary and dorsal vagal nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

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Anatomical evidence for an ipsilateral rubrospinal pathway and for direct rubrospinal projections to motoneurons in the cat.

In 11 cases [3H]leucine injections were made in various parts of the red nucleus (NR) and surrounding area. The autoradiographical tracing results confirmed the existence of a somatotopic organization in the location of the rubrospinal neurons. Moreover the results demonstrated direct NR projections to the most dorsolaterally located motoneuronal cell group in the C8 and upper T1 spinal segments and some ipsilaterally descending rubrospinal fibers terminating in the lateral part of the cervical intermediate zone.

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Spinal cord location of the motoneurons innervating the abdominal, cutaneous maximus, latissimus dorsi and longissimus dorsi muscles in the cat.

Horseradish peroxidase (HRP) injections were made in the rectus abdominis, obliquus externus, obliquus internus, transversus abdominis, cutaneous maximus, latissimus dorsi and the longissimus dorsi muscles in the cat. The results showed that motoneurons innervating the obliquus externus, obliquus internus and transversus abdominis muscles were located in greatly overlapping areas of midthoracic, caudal thoracic and upper lumbar spinal segments. These motoneuronal cell groups were present laterally in the ventral horn and at caudal thoracic and upper lumbar levels they bordered on the white matter. The location of the rectus motoneurons differed somewhat from the location of the other motoneuronal cell groups because they were also present at low cervical and upper thoracic levels and in the segments T12 to L3 they were found in the ventral horn medial to the other abdominal muscle motoneuronal cell group. At mid-thoracic levels rectus motoneurons were located in the same area as the other abdominal muscle motoneurons. Latissimus dorsi motoneurons were observed in a large cell group in the ventrolateral part of the ventral horn at the levels caudal C6 to rostral C8. Furthermore they were found in the segments T9 to L3 laterally in the ventral horn which is the same area in which the other abdominal muscle motoneurons except the rectus ones are located. Longissimus dorsi motoneurons were located in the most ventral portion of the ventral horn in all thoracic and upper 4 lumbar segments. The cutaneous maximus motoneurons were found in a cell group, located ventrolaterally in the ventral horn at the edge of the gray and white matter at the level caudal C8-rostral T1. This cell group corresponds to the caudal part of the ventral motor nucleus (VMN) of Matsushita and Ueyama (1973). Interestingly, labeled motoneurons were also present in the VMN after injecting HRP in the abdominal muscles as well as in the caudal (but not in the rostral) parts of the latissimus dorsi muscle but not in the longissimus dorsi injected cases. The possibility whether these motoneurons are labeled because of leakage of HRP to abdominal and caudal latissimus dorsi muscles is discussed. If leakage would not be the case, motoneurons in the VMN may be involved in specific functions of the abdominal muscles, such as the so-called steady state contractions.

Abdominal Muscles↗