Nucleus Prepositus Hypoglossi


BACKGROUND: The human nucleus prepositus hypoglossi (NPH), which is known to be a neural integrator of horizontal eye movement, may also serve vestibular function.  

The serotonergic system regulates processing in components of the vestibular nuclear complex, including the medial vestibular nucleus (MVe) and nucleus prepositus hypoglossi (PH).  

Labeled neurons were found in the rhombencephalic reticular formation, the vestibular nuclei, the nucleus prepositus hypoglossi, the nucleus of solitary tract, the spinal nucleus of trigeminal nerve and the dorsal column nuclei.  

PMD is located adjacent and medial to the nucleus prepositus hypoglossi (PH) in the dorsal medulla and is distinguished by the pattern of immunoreactivity of cells and fibers to several markers including calcium-binding proteins, a synthetic enzyme for nitric oxide (neuronal nitric oxide synthase, nNOS) and a nonphosphorylated neurofilament protein (antibody SMI-32).  

The unilateral MMI lesion in the nucleus prepositus hypoglossi and/or the medullary reticular formation caused contralesional shift of the eyes and ipsilesional nystagmus.  

A major inhibitory input to the LC is GABAergic, arising from the nucleus prepositus hypoglossi.  

These include visual input from the dorsolateral pons, and vestibular-oculomotor input from the medial vestibular nucleus (MVe) and the nucleus prepositus hypoglossi (Nph).  

Purkinje cells of zones 2 and 4 projected to the magnocellular and parvicellular parts of the medial vestibular nucleus, while some also innervated the lateral vestibular nucleus or nucleus prepositus hypoglossi.  

Moreover, WIN55212-2 suppressed the inhibition of noradrenergic cells produced by stimulation of the major gamma-aminobutyric acid (GABA)ergic afferent to the LC, the nucleus prepositus hypoglossi.  

Many studies have shown that the nucleus prepositus hypoglossi (PH) participates with the vestibular nuclear complex, the cerebellum and the oculomotor nuclei in the control of eye movements.  

Neurol., 492, 303-322], it was found that PAGdl specifically receives input from the nucleus prepositus hypoglossi, which plays a role in oculomotor control.  

Elsewhere in the vestibular nuclear complex (VNC) and in the nucleus prepositus hypoglossi (PrH) there are scattered labeled cells.  

The climbing fibers (CFs) that project from the dorsal cap of the inferior olive (IO) to the flocculus of the cerebellar cortex have been reported to be purely sensory, encoding "retinal slip." However, a clear oculomotor projection from the nucleus prepositus hypoglossi (NPH) to the IO has been shown.  

The ocular motor abnormalities may be explained by involvements of the nucleus prepositus hypoglossi, medial longitudinal fasciculus or efferent fibers from the vestibular nuclei, climbing fibers, and cells of the paramedian tracts..  

The DC receives excitatory signals from the ipsilateral nucleus of the optic tract (NOT) and inhibitory signals from the contralateral nucleus prepositus hypoglossi (NPH).  

The cytoarchitecture and the histochemistry of nucleus prepositus hypoglossi and its afferent and efferent connections to oculomotor structures are described.  

Afferents to the motoneurons arise from the vestibular nuclei, the oculomotor and abducens internuclear neurons, the mesencephalic and pontine burst neurons, the interstitial nucleus of Cajal, nucleus prepositus hypoglossi, the supraoculomotor area and the central mesencephalic reticular formation and the pretectum.  

Retrogradely labeled cells were also found in the nucleus prepositus hypoglossi (PPH), mainly contralaterally.  

Robust infection of the dorsal tegmental nucleus (DTN) and nucleus prepositus hypoglossi (PH) in these cases, but not in controls, at both survival intervals identified these nuclei as potential relays of vestibular input to the LMN.  

There were focal dense regions of fibers immunoreactive to calbindin in the medial and inferior nuclei, with an especially dense region of label at the border of the medial nucleus and the nucleus prepositus hypoglossi.  

BACKGROUND: The nucleus prepositus hypoglossi (NPH) is known to be a neural integrator of horizontal eye movements.  

Descending branch ramifications terminated in the caudal medial, parvicellular medial and descending vestibular nuclei, and the nucleus prepositus hypoglossi.  

The results confirm the suggestion about a substantial role of the nucleus prepositus hypoglossi in relaying afferent effects to the activity of locus coeruleus neurons..  

We argue that BT neurons in the nucleus prepositus hypoglossi/medial vestibular nucleus play an important role in the generation of unequal eye movements during disjunctive saccades, and carry appropriate information to shape the saccadic discharges of the abducens nucleus neurons to which they project..  

Moreover, immunoreactive cell bodies were found in the inferior colliculus, the raphe obscurus, the nucleus prepositus hypoglossi, and in the midline of the anterior medulla oblongata. In addition to the nuclei mentioned above, the highest densities of such immunoreactive fibers were located in the spinal trigeminal nucleus, the lateral reticular nucleus, the nucleus of the solitary tract, the superior colliculus, the substantia nigra, the nucleus ambiguus, the gracile nucleus, the cuneate nucleus, the motor hypoglossal nucleus, the medial and superior vestibular nuclei, the nucleus prepositus hypoglossi and the interpeduncular nucleus.  

Second, no double-labeled neurons were found following injections of DF in the medial VN and DTR in the nucleus prepositus hypoglossi (NPH) at the same time.  

After injections into the rVA zones, heavy anterograde labeling was found in the medial and descending vestibular nuclei, the nucleus prepositus hypoglossi, and the central region of the superior vestibular nucleus.  

It is possible that these properties depend on the synaptic drives generated by the major premotor inputs to AbMNs, namely position-vestibular-pause (PVP) cells and eye and head velocity (EHV) cells in the medial vestibular nucleus, and eye-position and burst-position cells in the nucleus prepositus hypoglossi (NPH).  

A previous analysis of nucleus prepositus hypoglossi (nph) lesions in monkeys found that the integration time constant for maintaining fixations decreased, while that for the vestibulo-ocular reflex (VOR) did not.  

Some of the termination areas in the reticular formation can be homologized with the mammalian inferior olive and the nucleus prepositus hypoglossi.  

A substantial number of retrogradely labeled neurons showing tyrosine hydroxylase (TH) immunoreactivity were found in the NTS and ventrolateral medulla (VLM) at levels caudal to the obex and in the locus coeruleus, while retrogradely labeled neurons without TH immunoreactivity were found in the VLM at levels rostral to the obex and in the nucleus prepositus hypoglossi.  

For horizontal gaze, neurons in the nucleus prepositus hypoglossi-medial vestibular nucleus region (NPH-MVN) play a vital role in this neural integrator function.  

In addition, the caudal dc receives a substantial GABAergic input from the nucleus prepositus hypoglossi (NPH).  

PKC delta-immunolabeled axons also terminated within the caudal medial and descending vestibular nuclei (MVN and DVN, respectively), the parasolitary nucleus (Psol), and the nucleus prepositus hypoglossi (NPH).  

The distribution of retrogradely labeled Purkinje cells revealed that efferent projections from the dorsal surface of the flocculus and the ventral paraflocculus to the superior vestibular nucleus, rostral medial vestibular nucleus, ventral lateral vestibular nucleus, and caudal aspect of the vestibular nuclear complex (caudal medial vestibular nucleus, inferior vestibular nucleus and nucleus prepositus hypoglossi) tended to correspond to previously identified climbing fiber zones [ Ruigrok et al.  

In the nucleus prepositus hypoglossi, all vestibular, abducens, cuneate, and lateral reticular nuclei, labeled neurons commingled with unlabeled ones.  

A medial descending noradrenergic bundle (MDB) projects from LC to LVN, the medial vestibular nucleus (MVN), group y and rostral nucleus prepositus hypoglossi (rNPH).  

The pontine reticular formation connected with the nucleus prepositus hypoglossi was studied in the rat using anterograde and retrograde tracer techniques. The area reciprocally connected with the nucleus prepositus hypoglossi was evident in the pontine reticular formation of the rat. The region had intensive reciprocal connections with the ipsilateral subthalamic region, the contralateral pontine reticular formation and the nucleus prepositus hypoglossi.  

Moderate trigeminal projections were observed in the small vestibular groups f, x and y/l and in the nucleus prepositus hypoglossi.  

In monkeys, using mainly electrophysiological methods, the roles of the frontal eye field, parietal eye field and supplementary eye field at the cortical level, and those of the paramedian pontine reticular formation, nucleus prepositus hypoglossi, interstitial nucleus of Cajal and superior colliculus at the brainstem level have been studied in great detail.  

For horizontal eye movements, the neural integrator is thought to reside in the rostral nucleus prepositus hypoglossi (nph) and project directly to the abducens nuclei.  

In addition, neurons in several areas of the medulla and caudal pons, including the retroambigual nucleus, medial and ventromedial reticular formation, nucleus prepositus hypoglossi, vestibular nuclei, and raphe nuclei, were infected by transynaptic passage of PRV from rectus abdominis motoneurons.  

The spatial distribution of ChAT-Ir within the VN of control cats showed darkly stained neurons and varicosities mainly located in the caudal parts of the medial (MVN) and inferior (IVN) VN, the nucleus prepositus hypoglossi (PH) and, to a lesser extent, in the medial part of the superior vestibular nucleus (SVN).  

They are largely confined to three heavily interconnected midbrain structures: 1) The interstitial nucleus of Cajal (NIC), 2) The nucleus prepositus hypoglossi (NPH), 3) The vestibular nuclei (VN).  

It has been suggested that the function of the nucleus prepositus hypoglossi (nph) is the mathematical integration of velocity-coded signals to produce position-coded commands that drive abducens motoneurons and generate horizontal eye movements.  

These neurons, which are located in the nucleus prepositus hypoglossi (NPH), spinal vestibular nucleus, cochlear complex, and gigantocellular and paragigantocellular nuclei of the reticular formation, express functional receptors for NGF and up-regulate the expression of trkA receptors after injection of NGF into targets.  

The clusters of the trained network are reminiscent of the small clusters or patches that have been found experimentally in the nucleus prepositus hypoglossi, where the neural integrator is located.  

A neuronal pathway from the nucleus prepositus hypoglossi (PH) to the superior colliculus (SC) has been documented in previous studies using retrogradely transported tracer methods.  

Direct projections from NOT to the ipsilateral nucleus prepositus hypoglossi (ppH) appeared to be weak, but retrograde tracer injections into rostral ppH verified this projection; furthermore, the injections demonstrated that AON efferents also enter this area.  

The projection from the nucleus prepositus hypoglossi (PH) to the superior colliculus (SC) has been proposed to provide a feedback control of collicular saccadic activities.  

These neurons also projected to the medullary reticular formation, caudal nucleus prepositus hypoglossi, and dorsal and ventral paramedian reticular nucleus.  

The rat DC receives a prominent input from the nucleus prepositus hypoglossi (NPH); part of these axon terminals are immunoreactive for choline acetyltransferase (ChAT) and part of them are GABAergic.  

The aim of this study was to evaluate the validity of this hypothesis by checking whether the sensitivity to eye position of the neurones of the nucleus prepositus hypoglossi (NPH) (the main component of the system integrating the different incoming velocity signals) would be the same regardless of the type of versional movement.  

The distribution of immunoreactivity to calbindin, calretinin, and parvalbumin in the vestibular nuclear complex and the adjacent nucleus prepositus hypoglossi was studied in rats and gerbils.  

It also gave rise to moderate or weak terminal fields in the vestibular complex, the nucleus prepositus hypoglossi, the inferior olive, and the magnocellular reticular formation, as well as cell groups scattered along the paramedian tracts in the pons and the pontine and medullary raphe.  

It has been reported that the nucleus prepositus hypoglossi (PrH) sends GABAergic inputs to the LC.  

The prearcuate cortex projects to several brainstem areas which also receive projections from the caudal fastigial nucleus, including the supraoculomotor periaqueductal gray matter, superior colliculus, medial nucleus reticularis tegmenti pontis, dorsomedial basilar pontine nucleus, dorsolateral basilar pontine nucleus, nucleus reticularis pontis caudalis, pontine raphe, and nucleus prepositus hypoglossi.  

The role of the neuronal activity of nucleus prepositus hypoglossi (NPH) in optokinetic stimulation (OKS) and the changes of the activity between OKS and off-OKS (resting condition) were investigated in 5 adult cats.  

Descending fibers from the NOT consisted of two major pathways: (1) fibers descended medially from the injection site through the reticularis pontis oralis to reach the lateral part of the ipsilateral nucleus reticularis tegmenti pontis; (2) fibers projecting into the dorsal cap of inferior olive, by far the greatest number of labeled fibers, descended ventrally along the lateral border of the reticularis pontis oralis and reached the medial lemniscus where they descended further and branched into the dorsolateral pontine nucleus, the lateral part of the nucleus reticularis tegmenti pontis, the peduncular pontine nucleus, the lateral pontine nucleus, the nucleus prepositus hypoglossi, the medial vestibular nucleus and finally the dorsal cap of the inferior olive.  

EBNs also project to the nucleus prepositus hypoglossi while vertical MLBs also project to the interstitial nucleus of Cajal (NIC).  

Following biocytin injections into the NOT, labeled fibers were observed in each of the following efferent pathways: 1) those that project to the contralateral NOT via the posterior commissure; 2) those that course through the nucleus pontis orklis to terminate in the Edinger-Westphal complex and nucleus reticularis tegmenti pontis; and 3) those that descend via the medical lemniscus to the level of the medulla to terminate in the dorsal cap of the inferior olive, during which their axons branch to the dorsolateral pontine nucleus, nucleus prepositus hypoglossi, and the nucleus pontis caudalis, superior and lateral. Furthermore, differences in the distribution of labeled cells in the NOT were observed following WGA-HRP injections into the nucleus prepositus hypoglossi and medial vestibular nucleus. On the other hand, labeled cells were recognized in the part of the caudal NOT following the tracer injections into the nucleus prepositus hypoglossi.  

In the cerebellar nuclei, vestibular nuclei and nucleus prepositus hypoglossi Purkinje cell terminals were found apposed to GABAergic and glycinergic neurons as well as to larger non-GABAergic, non-glycinergic neurons.  

The efferent projections of the nucleus of the optic tract (NOT) and dorsal terminal nucleus of the accessory optic system (DTN) to the contralateral NOT-DTN, ipsilateral inferior olive (IO), ipsilateral nucleus prepositus hypoglossi (NPH), and ipsilateral dorsal lateral geniculate nucleus (LGNd) were examined in pigmented rats and in cats by using anterograde and retrograde tract tracing, as well as extracellular recording and electrical stimulation.  

All injections into the LTR traced afferents from the vestibular nuclei and from the nucleus prepositus hypoglossi. Predominant projections were derived from the ipsilateral nucleus prepositus hypoglossi and the ipsilateral medial vestibular nucleus, whereas the observed inputs from the inferior, lateral, and superior vestibular nuclei were much weaker. Our results suggest that afferents from the deeper layers of the superior colliculus are probably the source of visual signals in the LTR and that head movement-related responses are likely to be derived from the nucleus prepositus hypoglossi and the medial vestibular nucleus..  

The interstitial nucleus of Cajal (INC) and the nucleus prepositus hypoglossi (nph) are key elements in the vertical and horizontal oculomotor neural integrators, respectively.  

The nucleus prepositus hypoglossi, dorsal group y, ventral dentate nucleus, and medial vestibular nucleus all project to both the oculomotor complex and inferior olive.  

These double-labelled cells were found in the paramedian region, lateral reticular field, the nucleus prepositus hypoglossi and in the rostral nucleus of the tractus solitarius.  

Comparison of labeling patterns in the perihypoglossal nuclei following HRP injections into various sublobules of the paramedian lobule suggests that projections from the perihypoglossal nuclei to the paramedian lobule exist and that some degree of topographic organization is present exclusively in bilateral projections from the caudal part of nucleus prepositus hypoglossi. It is significant that in the ipsilateral nucleus prepositus hypoglossi, two groups of cells projecting to zone C2 are arranged rostrocaudally between three other groups projecting to zone D1..  

Intracellular recordings were made from guinea pig nucleus prepositus hypoglossi in vitro, where we have described a 5-HT-mediated IPSP.  

The NOT sent lighter, but consistent, projections to other visual and oculomotor-related areas including, from rostral to caudal, the ipsilateral pregeniculate nucleus, the contralateral NOT, the lateral and medial terminal nuclei of the accessory optic system bilaterally, the ipsilateral dorsolateral pontine nucleus, the ipsilateral nucleus prepositus hypoglossi, and the ipsilateral medial vestibular nucleus. Our results indicate that the NOT can influence brainstem preoculomotor pathways both directly through the medial vestibular nucleus and nucleus prepositus hypoglossi and indirectly through both climbing and mossy fiber pathways to the cerebellar flocculus.  

Vestibular nucleus injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin indicated (1) that a predominantly ipsilateral projection to the caudal dorsal cap originates bilaterally from the pars beta of the lateral vestibular nucleus and the rostroventral aspect of the rostral medial vestibular nucleus, (2) that the medial half of the caudal medial vestibular nucleus is the source of a predominantly contralateral projection to dorsal cap, (3) that the caudal aspect of nucleus prepositus hypoglossi contributes a predominantly ipsilateral projection to the medial accessory olive and (4) that the rostral aspect of inferior vestibular nucleus and the dorsal and lateral aspects of the caudal medial vestibular nucleus project to nucleus beta of the medial accessory olive.  

For horizontal eye movements, previous observations led to the hypothesis that the legendary neural integrator necessary for correct gaze holding, adequate vestibuloocular reflex (VOR), and optokinetic nystagmus, was located in the region of the complex formed by the nucleus prepositus hypoglossi (NPH) and the medial vestibular nucleus (MVN).  

Injecting WGA-HRP into the abducens nucleus and the surrounding tissue labeled many cells in SC, PPRF, MVN, FN, and nucleus prepositus hypoglossi (NPH).  

Spontaneous eye movements were recorded before and after a microinjection (0.1-0.2 microliter) of either APV (an NMDA receptor antagonist) or NBQX (a non-NMDA receptor antagonist) into the nucleus prepositus hypoglossi (NPH) of the alert cat.  

Intracellular recordings were made from neurons of the nucleus prepositus hypoglossi in slices of guinea pig medulla.  

The caudal dorsal cap is predominantly involved in the horizontal optokinetic reflex; it receives most of its GABAergic input from the nucleus prepositus hypoglossi.  

DR fibers project lightly to nucleus cuneiformis, nucleus prepositus hypoglossi, nucleus paragigantocellularis, nucleus reticularis ventralis, and hypoglossal nucleus.  

Previously, microinjections of kainic acid (KA) into the region of the nucleus prepositus hypoglossi (NPH) and of the medial vestibular nucleus (MVN) were found to induce a horizontal gaze-holding failure both in the cat and in the monkey.  

The brainstem origin of CRF-immunoreactive mossy fiber terminals was suggested by numerous CRF-immunoreactive perikarya located in the medial, lateral and descending vestibular nuclei, nucleus prepositus hypoglossi, nucleus x, paramedian reticular nucleus, gigantocellular reticular nucleus, lateral reticular nucleus, and raphé nuclei. Horseradish peroxidase (HRP) injections into the posterior vermis double labeled CRF-immunoreactive neurons in the caudal medial and descending vestibular nuclei and nucleus prepositus hypoglossi. HRP injections into the flocculus double labeled more CRF-immunoreactive neurons in the nucleus prepositus hypoglossi than in the vestibular nuclei.  

Following biocytin injections into NOT, labeled fibers were observed in each of the following efferent pathways: (1) those that project to the contralateral NOT via the posterior commissure; (2) those that course through the nucleus reticularis pontis oralis to terminate in the nucleus reticularis tegmenti pontis; and (3) those that descend via the medial lemniscus to the level of the medulla to terminate in the dorsolateral pontine nucleus, nucleus prepositus hypoglossi, medial vestibular nucleus and the inferior olive.  

We conclude (1) that the vestibular commissure is a component of the gaze-holding system, (2) that the vestibular commissure is less essential for gaze holding than other structures as the nucleus prepositus hypoglossi, and (3) that the horizontal gaze-holding system consists of two halves, each being more active in ipsilateral than in contralateral gaze..  

In rats and rabbits we injected iontophoretically the orthograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the medial and descending vestibular nuclei (MVN, DVN) as well as the nucleus prepositus hypoglossi (NPH) in order to trace the possible origin of the cholinergic projection.  

The projection from the nucleus prepositus hypoglossi to the dorsal cap was studied in the light microscope by anterograde tracing of Phaseolus vulgaris-leucoagglutinin and lesion-induced depletion of glutamic acid decarboxylase immunoreactivity, and in the electron microscope by anterograde tracing of wheat germ agglutinin-coupled horseradish peroxidase combined with GABA immunocytochemistry. We show that the nucleus prepositus hypoglossi projects bilaterally to the dorsal cap, contralaterally to the ventrolateral outgrowth, and ipsilaterally to the medial accessory olive. After lesioning of the nucleus prepositus hypoglossi, the caudal dorsal cap was depleted of most of its glutamic acid decarboxylase-immunoreactive terminals while the rostral dorsal cap and the ventrolateral outgrowth were depleted of a minor part. Ultrastructural analysis indicates that the majority, but not all, of the terminals from the nucleus prepositus hypoglossi in the dorsal cap are GABA-positive. None of the terminals from the nucleus prepositus hypoglossi was found to form a crest synapse, although synapses of this kind were predominantly formed by GABAergic terminals. This study shows that the dorsal cap receives a major inhibitory input from the nucleus prepositus hypoglossi, the terminals of which are located at strategic positions on the olivary neurons..  

Injections of the tracer into the superficial layers of the SC yielded retrogradely labeled cells only in the rostral part of the contralateral INT; by contrast, the injection confined to the deep layers produced labeling of cells exclusively in the nucleus prepositus hypoglossi (PH).  

Labelled cells were found in the reticular formation and adjacent nucleus coeruleus, the parabrachial nuclei, raphe nuclei (magnus, dorsalis and centralis superior), nucleus prepositus hypoglossi, lateral hypothalamus and hippocampal CA1..  

ENK-ir neurons were also present in nuclei of the rostral medulla reported to be major afferents of the LC, the nucleus prepositus hypoglossi (PrH), and the nucleus paragigantocellularis (PGi).  

These regions include the nucleus prepositus hypoglossi (NPH), the medial vestibular nucleus (MVN), and their common border (the "marginal zone").  

In the lower brain stem, stem axons of type Ib and Ic neurones passed in the dorsal part of the reticular formation or in the medial longitudinal fasciculus and projected collaterals to the dorsal part of the nucleus reticularis pontis caudalis (NRPC) and the nucleus reticularis gigantocellularis (NRG) and the reticular formation underlying the nucleus prepositus hypoglossi (PH) and the raphe region.  

Some of them projected to the inferior olive and the nucleus prepositus hypoglossi as well.  

The nucleus prepositus hypoglossi was included in the analysis. In the nucleus prepositus hypoglossi and in the medial vestibular nucleus 6% of the number of labeled neurons contained both tracers, against 4% in the descending vestibular nucleus.  

NOT-DTN neurons relay visual information to the vestibular nuclei via the nucleus prepositus hypoglossi and to the flocculus via the dorsal cap of the inferior olive.  

Scanty projections could be detected within the vestibular nuclei as well as within the perihypoglossal nuclei except for the nucleus prepositus hypoglossi.  

We have investigated the possibility that GABAergic neurones may be involved in two ascending projections to the superior colliculus, originating in the nucleus prepositus hypoglossi and in the periparabigeminal area of the mesencephalon, respectively.  

There had been no reports of a cardiovascular role for the nucleus prepositus hypoglossi; thus, we sought to determine if electrical or chemical stimulation of that nucleus or the adjacent medial vestibular nucleus altered arterial pressure or heart rate in 24 anesthetized rats. Both types of stimuli to the caudal, but not the rostral, pole of the nucleus prepositus hypoglossi or to the medial vestibular nucleus elicited an increase in arterial pressure; bradycardia accompanied the former and tachycardia the latter. Both the nucleus prepositus hypoglossi and medial vestibular nucleus may participate in central cardiovascular regulation..  

Previous studies showed that the nucleus locus coeruleus (LC) receives two major afferent inputs from 1) nucleus paragigantocellularis and 2) nucleus prepositus hypoglossi, both in the rostral medulla.  

Anatomical and electrophysiological data have shown that, in the guinea pig as well as in the cat, the nucleus prepositus hypoglossi gives rise to a disynaptic ascending projection to the superior colliculus via the peri-parabigeminal area in the mesencephalon.  

Retrograde labeling confirmed recent findings that the major afferents to the locus coeruleus are present in the ventrolateral (nucleus paragigantocellularis) and dorsomedial medulla (nucleus prepositus hypoglossi), areas containing the C1 and C3 adrenergic cell groups, respectively.  

Tract-tracing and electrophysiology studies have revealed that major inputs to the nucleus locus coeruleus (LC) are found in two structures, the nucleus paragigantocellularis (PGi) and the perifascicular area of the nucleus prepositus hypoglossi (PrH), both located in the rostral medulla.  

The present study, using anterograde and retrograde tracing of wheat germ agglutinin-conjugated horseradish peroxidase, found that the medullary nucleus prepositus hypoglossi (PH), whose neurons are known to have eye-movement-related information, projects densely to PPT, and PPT has reciprocal projections to PH.  

While the heaviest anterogradely labeled ascending projections were observed to the contralateral ventral posterolateral nucleus of the thalamus, pars oralis (VPLo), efferent projections were also observed to the contralateral ventrolateral thalamic nucleus (VLc) and central lateral (CL) nucleus of the thalamic intralaminar complex, magnocellular (and to a lesser extent parvicellular) red nucleus, nucleus of Darkschewitsch, zona incerta, nucleus of the posterior commissure, lateral intermediate layer and deep layer of the superior colliculus, dorsolateral periaqueductal gray, contralateral nucleus reticularis tegmenti pontis and basilar pontine nuclei (especially dorsal and peduncular), and dorsal (DAO) and medial (MAO) accessory olivary nuclei, ipsilateral lateral (external) cuneate nucleus (LCN) and lateral reticular nucleus (LRN), and to a lesser extent the caudal medial vestibular nucleus (MVN) and caudal nucleus prepositus hypoglossi (NPH), and dorsal medullary raphe.  

Terminal label was evident in the pretectal olivary nucleus, nucleus of the optic tract, nucleus raphe interpositus (omnipause region), nucleus prepositus hypoglossi, the perioculomotor cap of the central gray, dorsal central gray, nucleus reticularis tegmenti pontis, nucleus reticularis pontis oralis, and to multiple nuclei of the basis pontis (most densely to the dorsomedial nucleus).  

Intracellular recordings were made from neurones of the nucleus prepositus hypoglossi (PH) in slices of guinea-pig brain.  

In addition to the restricted distribution of labeled Purkinje cells in lobules VI and VII of the posterior lobe vermis ("oculomotor vermis"), retrogradely labeled cells were present in the dorsolateral pontine nucleus (DLPN), dorsomedial pontine nucleus (DMPN), nucleus reticularis tegmenti pontis (NRTP), pontine raphe (PR), paramedian nucleus reticularis pontis caudalis (NRPC), nucleus prepositus hypoglossi (NPH), subnucleus b of the medial accessory olivary nucleus (sbMAO), and vestibular complex (VC).  

A few cells were labeled in the vestibular nuclei and nucleus prepositus hypoglossi bilaterally.  

In this study we have used retrogradely transported horseradish peroxidase (HRP) to investigate whether the nucleus prepositus hypoglossi of a lateral-eyed mammal projects to the oculomotor and trochlear nuclei. After the injection of HRP in the oculomotor nucleus of rabbits, labelled neurons were found bilaterally in the nucleus prepositus hypoglossi, though they were more numerous on the ipsilateral side.  

The largest numbers of retrogradely labeled neurons within the PH complex were found in the contralateral nucleus prepositus hypoglossi (NPH), in the laterally adjacent medial vestibular nucleus, and in the ventrally adjacent reticular formation (the nucleus reticularis supragigantocellularis).  

Impairment of the velocity storage element attributable to damage to the vestibular nucleus and nucleus prepositus hypoglossi may account for this permanent effect on the vestibulo-ocular reflex..  

Recent anatomic studies in our laboratory (Aston-Jones et al., 1986) identified the nucleus prepositus hypoglossi (PrH) in the dorsomedial medulla as a major afferent of the locus coeruleus (LC).  

These fibers may arise from cells in the nucleus prepositus hypoglossi or vestibular nuclei..  

Three populations of labeled cells were found: one which projected to the inferior olive, a second to the nucleus prepositus hypoglossi, and a third which projected by means of a bifurcating axon to both of these structures.  

In the present study this effect of nicotine was attenuated (to about 25% of control response) by injection of lidocaine into the nucleus paragigantocellularis (PGi) whereas injection into the nucleus prepositus hypoglossi (PrH) had no effect in this regard.  

Serotonin (5-HT) induced a slow depolarization when superfused onto neurons of the rat brainstem nucleus prepositus hypoglossi (PH) in vitro.  

Previous studies reported afferents to LC from the nucleus tractus solitarius (NTS), while more recent anatomic experiments indicate that the area of the nucleus prepositus hypoglossi (PrH), but not the NTS, provides robust innervation of LC.  

Motoneurons were prevalent in the hypoglossal nucleus and the other type prevailed in the adjoining nucleus prepositus hypoglossi.  

By contrast, when WGA-HRP injections were made into the lateral rectus muscle, retrogradely labeled cells appeared in the mesencephalic central gray, the oculomotor complex, the pontine reticular nuclei, the medial and lateral vestibular nuclei, and the nucleus prepositus hypoglossi, in addition to strong labeling of cells in the ipsilateral abducens nucleus and the accessory abducens nucleus.  

Some of the rostral and caudal stem axons had collaterals which projected to the contralateral nucleus prepositus hypoglossi (PH), nucleus raphe pontis, or medullary reticular formation.  

In the caudal medulla, labeled fibers and their terminals were observed in the nucleus prepositus hypoglossi, the nucleus intercalatus and the inferior olive.  

In one sFEF case, very small patches of label were located in the supragenual nuclei anterior to the abducens nuclei and in the ipsilateral nucleus prepositus hypoglossi posterior to the abducens nucleus.  

Following iontophoretic injections of the retrograde tracer Fluoro-gold into the rat locus coeruleus (LC), retrogradely labeled neurons were seen predominantly in the area of C1 adrenergic neurons in the ventrolateral medulla (nucleus paragigantocellularis; PGi) and in the area of C3 adrenergic neurons in the dorsomedial medulla (nucleus prepositus hypoglossi; PrH).  

The primary goal of this investigation was to identify the areas of the brainstem and cerebellum that provide afferent projections to the nucleus prepositus hypoglossi in primates.  

The heterogeneous cytoarchitecture of nucleus prepositus hypoglossi and its multiplicity of afferent and efferent connections to oculomotor structures are described.  

Retrogradely labeled cells were observed in numerous oculomotor-related structures, including the prerubral field (rostral interstitial nucleus of the medial longitudinal fasciculus), nucleus of Darkschewitsch, nucleus of the posterior commissure, deep superior colliculus, supraoculomotor ventral periaqueductal gray, contralateral paramedian pontine reticular formation, pontine raphe and dorsal medial pontine tegmentum medial to the abducens nucleus (purported to contain omnipause neurons), cell group Y, and the perihypoglossal complex (nucleus prepositus hypoglossi).  

At stage 50, a possible anuran homologue of the mammalian nucleus prepositus hypoglossi was found to project to the cerebellum.  

Large numbers of neurons were labeled in the ventral margin of the nucleus prepositus hypoglossi in the cat and in the common margin of the nucleus prepositus and the medial vestibular nucleus in the monkey, a region we call the marginal zone.  

The paramedian pontine reticular formation projects with bilateral symmetry to the cerebellar lobules VI, VII and the crura I and II, and heavily to the medial aspect of predominantly the ipsilateral reticular formation in the lower brain stem including specific targets as the nucleus reticularis paramedianus, the nucleus prepositus hypoglossi, the nucleus intercalatus, the nucleus of Roller, the nucleus supragenualis and the dorsal cap of the inferior olive.  

Many nuclei known to project to the cerebellum, including the nucleus reticularis tegmenti pontis, the medial accessory inferior olive, the nucleus prepositus hypoglossi, and many areas of the reticular formation contained positive neurons.  

The afferent and efferent connections of the nucleus prepositus hypoglossi with brainstem nuclei were studied using anterograde and retrograde axonal transport techniques, and by intracellular recordings and injections of horseradish peroxidase into prepositus hypoglossi neurons.  

The greatest numbers of labeled neurons were in the vestibular complex and the nucleus prepositus hypoglossi.  

Following injections in the medial and descending vestibular nuclei, terminal labeling was found ipsilaterally in the dorsomedial cell column, subnucleus beta and the caudal medial accessory olive, while the latter also received afferents from the nucleus prepositus hypoglossi. The dorsal cap was labeled exclusively from the contralateral nucleus prepositus hypoglossi.  

Following horseradish peroxidase gel implants in prearcuate cortex involving the frontal eye field (area 8) in Old and New World monkeys, bilateral anterograde labelling was observed in the nucleus prepositus hypoglossi, an important preoculomotor nucleus..  

Experiments in 5 monkeys revealed 3 major sources of input: (1) bilateral projections from the so-called frontal eye field (FEF), which is situated in the frontal cortex around the arcuate sulcus; (2) the intermediate and deep layers of mainly the contralateral superior colliculus; and (3) ipsilateral projections from brainstem structures such as the accessory oculomotor nuclei (nucleus interstitialis of Cajal, nucleus of Darkschewitsch, and nucleus of the posterior commissure), the mesencephalic reticular formation, the vestibular nuclei, the nucleus prepositus hypoglossi, and the cerebellar fastigial nucleus.  

The medial rectus motor division of the ipsilateral oculomotor nucleus showed an increase whereas the ipsilateral abducens and the ipsilateral nucleus prepositus hypoglossi exhibited a decline in their utilization rates.  

Following HRP injections into the centre médian nucleus (CM), major labeled neurons were found in the areas 4 gamma, 6a beta, and the orbital gyrus ipsilaterally, and in the EPN, rostral and rostrolateral parts of the thalamic reticular nucleus, locus ceruleus, nucleus reticularis pontis oralis et caudalis and nucleus prepositus hypoglossi bilaterally.  

arise from: the labyrinth, through the vestibular nerve (vestibulo-ocular reflex); the neck, through the dorsal part of the medullary tegmentum (cervico-ocular reflex); the peripheral retina and the visual pathways (for the vestibular contribution of optokinetic nystagmus), perhaps via the pretectum, the nucleus reticularis tegmenti pontis (N.R.T.P.) and/or the nucleus prepositus hypoglossi (N.P.H.) (visuo-ocular reflex).  

In the control animals the nucleus caudatus putamen, globus pallidus, hippocampus, nuclei of amygdala, nuclei hypothalami, substantia grisea centralis, griseum pontis, nucleus trapezoideus, nucleus prepositus hypoglossi, nucleus parabrachialis, nucleus vestibularis, nucleus nervi hypoglossi, nucleus dorsalis nervi vagi, nucleus olivaris and nucleus centralis superior are found to be very rich in ATPase.  

Furthermore, distinct bilateral ascending projections of the nucleus prepositus hypoglossi were demonstrated.  

A few neurons were labeled in a restricted region of the causal part of the nucleus prepositus hypoglossi and in the nucleus reticularis medullaris ventralis.  

The major input sources to the pause neuron region were nucleus prepositus hypoglossi, medial vestibular nucleus, gigantocellular reticular nucleus, parvocellular reticular nucleus, nucleus reticularis tegmentis pontis, nucleus reticularis pontis caudalis, nucleus reticularis pontis oralis, and superior colliculus.  

Our results for neurons projecting to the spinal cord (spinal-projecting neurons) from the nucleus ambiuus, dorsal motor nucleus of the vagus, superior vestibular nucleus and nucleus f, nucleus Darshevch, nucleus Rolleri, nucleus prepositus hypoglossi, and nucleus of the posterior commissure have been reported before in other mammals but not in rats.  

The responses of 47 nucleus prepositus hypoglossi neurons to vestibular optokinetic stimulations in the horizontal plane were recorded in immobilized, pigmented rats.  

Distinct but light labeling was seen in raphe pallidus and obscurus, nucleus prepositus hypoglossi, nucleus gigantocellularis pars ventralis, and the ventral (medial) parabrachial nucleus.  

Furthermore, a secondary trigeminocerebellar projection arising in the descending trigeminal nucleus, a cerebellar projection arising in the dorsal column nucleus, a small projection arising in a possible primordium of the mammalian nucleus prepositus hypoglossi, a raphecerebellar projection, and a small cerebellar projection originating in the ipsilateral mesencephalic tegmentum were demonstrated.  

Caudally, there are terminal fields over the paramedian reticular formation, the caudal part of the medial accessory nucleus of the inferior olivary complex, the nucleus prepositus hypoglossi, and the nucleus reticularis paragigantocellularis dorsalis caudal and ventromedial to the abducens nuclei.  

(2) Monosynaptic projections from the superior colliculus and some of the pretectal nuclei (nucleus of the optic tract, olivary pretectal nucleus) to the nucleus prepositus hypoglossi may constitute polysynaptic visual afferents to the VN, which would account for the residual visual sensitivity of the VN neurons after cerebellar or inferior olivary lesions..  

In the experimental animals a large number of boutons in the rostral part of the nucleus prepositus hypoglossi (Ph) ipsilateral to the floccular lesion showed degenerative changes.  

Large injections of HRP into the thalamus centered on the border region between the ventrobasal complex and the caudal ventrolateral nucleus resulted in bilateral retrograde labeling of cells in the vestibular nuclear complex and the nucleus prepositus hypoglossi (PH).  

The retrograde transport of fluorescent substances was used in order to investigate divergent axon collaterals of neurons in the nucleus prepositus hypoglossi (Ph).  

The interstitial nucleus of the vestibular nerve, the nucleus prepositus hypoglossi and the nucleus intercalatus project to all lobules..  

Rhombencephalic targets of TBSNs include the medial pontine and bulbar reticular formation, the abducens nucleus, the nucleus reticularis tegmenti pontis and the nucleus prepositus hypoglossi.  

These were mainly from the nucleus prepositus hypoglossi and adjacent pontine reticular formation, but also included projections from the medial vestibular an abducens nuclei and possibly subthalamic regions such as the zona incerta and fields of Forel.  

The generation time of neurons of the nucleus prepositus hypoglossi overlaps with that of the medial vestibular nucleus.  

These results suggest (1) primary position upbeat nystagmus is due to a defect in the upward smooth pursuit system, (2) the lower brain stem at the level of the inferior olives and nucleus prepositus hypoglossi is important in the mediation of vertical pursuit, and (3) primary position upbeat nystagmus can result from damage to several nuclei and interconnecting pathways in the caudal brain stem and midline cerebellum involved in control of vertical smooth pursuit..  


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