Brainstem afferents to the lateral mesencephalic tegmental region of the cat

The lateral mesencephalic tegmental region (LTR) is a part of the midbrain reticular formation characterized by the presence of neurons exhibiting head movement-related discharge modulation. In addition, the LTR contains directionally selective visual units. Possible sources for these vestibular and visual signals were studied by retrograde axonal transport of horseradish peroxidase and three different fluorescent tracers (rhodamine, fast blue, and fluorogold) injected into various parts of the LTR. 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. Further inputs to the LTR originated in the deep and intermediate layers of the ipsilateral superior colliculus and the ipsilateral periaqueductal gray, the contralateral LTR, and the contralateral marginal nucleus of the brachium conjunctivum. Tracer deposits in medial parts of the tegmentum neighboring the LTR never produced the pattern of afferents observed after injections into the LTR. 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. © 1995 Wiley-Liss, Inc.     

Projections from brainstem nuclei to the nucleus paragigantocellularis lateralis in the cat

Afferent projections from the pons and medulla to the nucleus paragigantocellularis lateralis (PGL) have been mapped in the cat using retrograde transport of horseradish peroxidase (HRP). In the caudal medulla, the major sources of afferents were the medial and lateral divisions of the solitary nuclei complex and the contralateral trigeminal nucleus caudalis. Labelled cells were also present in the dorsal column nuclei, nucleus intercalatus and praepositus hypoglossi but this may have been due to uptake of HRP into fibres of passage. In the dorsolateral medulla and pons, neurones in the vestibular complex and in the parabrachial nucleus were labelled bilaterally. Nucleus raphe magnus and raphe obscurus were both found to send projections to the PGL and labelled cells were also present throughout the pontine and medullary reticular nuclei as well as in PGL on the side opposite to the injection of HRP. These findings are discussed in relation to the role of the PGL in cardiovascular regulation and in the control of pain.     

Organisation of reciprocal connections between trigeminal and vestibular nuclei in the rat.

In order to study the connection patterns between the sensory trigeminal and the vestibular nuclei (VN), injections of anterogradely and/or retrogradely transported neuronal tracers were made in the rat. Trigeminal injections resulted in anterogradely labelled fibres, with an ipsilateral preponderance, within the VN: in the ventrolateral part of the inferior nucleus (IVN), in the lateral part of the medial nucleus (MVN), in the lateral nucleus (LVN) with a higher density in its ventral half, and in the superior nucleus (SVN), more in the periphery than in the central part. Moderate trigeminal projections were observed in the small vestibular groups f, x and y/l and in the nucleus prepositus hypoglossi. Additional retrogradely labelled neurones were seen in the IVN, MVN, and LVN, in the same regions as those receiving trigeminal afferents. Morphological analysis of vestibular neurones demonstrated that vestibulo-trigeminal neurones are relatively small and belong to a different population than those receiving projections from the trigeminal nuclei. The trigeminovestibular and vestibulo-trigeminal relationships were confirmed by tracer injections in the VN. The results show that, in the VN, there is sensory information from facial receptors in addition to those reported from the neck and body. These facial afferents complement those from the neck and lower spinal levels in supplying important somatosensory information from the face and eye muscles. The oculomotor connections of the respective zones of the VN receiving trigeminal afferents suggest that sensory inputs from the face, including extraocular proprioception, may, through this pathway, influence the vestibular control of eye and head movements.     

Projections of the parietal cortex on the vestibular complex in Macaca

Connections of parietal cortex (especially posterior part of area 7) with subcortical structures related with vestibular function were examined in four monkeys (Macaca Fascicularis), by means of anterograde labeling with HRP and tritated amino-acids tracers. Posterior parietal cortex was found to have direct efferent projections onto vestibular nuclei complex and prepositus hypoglossi nucleus. These efferences were distributed bilaterally with an ipsilateral preponderance. The labeled terminals were organized in precise patterns in vestibular nuclei in such a way that two groups of cortical efferences could be distinguished: the first one terminates on vestibular nuclei related with the cervico-spinal motor system and the second one terminates on both prepositus hypoglossi nucleus and vestibular nuclei involved in vestibulo-ocular functions. These latter efferent projections of parietal cortex onto vestibular nuclei complex could account for the role played by the posterior part of area 7 in the modulation of the vestibulo-ocular reflex.     

Ascending and descending projections of the lateral vestibular nucleus in the frog Rana esculenta

The lectin Phaseolus vulgaris leucoagglutinin was injected into the frog lateral vestibular nucleus (LVN) to study its antero- and retrograde projections. The following new observations were made. 1) In the diencephalon, vestibular efferents innervate the thalamus in a manner similar to that of mammalian species. The projections show a preference for the anterior, central, and ventromedial thalamic nuclei. 2) In the mesencephalon, vestibular fibers terminate in the tegmental nuclei and the nucleus of medial longitudinal fascicle. 3) In the rhombencephalon, commissural and internuclear projections interconnect the vestibular nuclei. Some of the termination areas in the reticular formation can be homologized with the mammalian inferior olive and the nucleus prepositus hypoglossi. Another part of the vestibuloreticular projection may transmit vestibular impulses toward the vegetative centers of the brainstem. A relatively weak projection is detected in the spinal nucleus of the trigeminal nerve, dorsal column nuclei, and nucleus of the solitary tract. 4) In the spinal cord, vestibular terminals are most numerous in the ipsilateral ventral horn and in the triangular area of the dorsal horn. 5) The coincidence of retrogradely labeled cells with vestibular receptive areas suggests reciprocal interconnections between these structures and the LVN. 6) In seven places, the LVN projections overlap the receptive areas of proprioceptive fibers, suggesting a convergence of sensory modalities involved in the sense of balance.     

Nucleus prepositus neurons projecting to the oculomotor and trochlear nuclei in rabbits

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 majority of these neurons were labelled in the rostral part of the propositus nucleus and were dispersed predominantly in the lateral and ventral zone of the nucleus. Neurons were also labelled in the prepositus nucleus after injection of HRP in the trochlear nucleus. These data were compared with those for frontal-eyed mammals and birds and suggest that the said projections are less well developed in species that possess panoramic vision and a lesser degree of binocular yoking.     

Projections of purkinje cells in the translation and rotation zones of the vestibulocerebellum in pigeon (Columba livia)

Previous electrophysiological studies have shown that the pigeon vestibulocerebellum (ventral uvula, nodulus, and flocculus) can be divided into two parasagittal zones based on responses to optic flow stimuli. The medial zone (ventral uvula and nodulus) responds best to optic flow resulting from self-translation, whereas the lateral zone (flocculus) responds best to optic flow resulting from self-rotation. In this study we investigated the projections of the Purkinje cells in the translation and rotation zones of the vestibulocerebellum by using the anterograde tracer biotinylated dextran amine. Extracellular recording of Purkinje cell activity (complex spikes) in response to large-field visual stimuli were used to identify the injection sites. Injections into the translation zone resulted in extremely heavy terminal labeling in the cerebellovestibular process adjacent to the medial cerebellar nucleus. A moderate amount of terminal labeling was found in the medial cerebellar nucleus, the superior vestibular nucleus (laterally, dorsally, and medially), and the descending vestibular nucleus, particularly in the lateral half. Light terminal labeling was observed in the dorsolateral vestibular nucleus, the medial vestibular nucleus, the tangential nucleus, and the lateral vestibular nucleus pars ventralis. Injections into the rotation zone resulted in heavy terminal labeling in the superior vestibular nucleus (particularly dorsally and medially), the descending vestibular nucleus (particularly medially), and the medial vestibular nucleus. A moderate amount of terminal labeling was seen in the cerebellovestibular process adjacent to the lateral cerebellar nucleus, and the dorsolateral vestibular nucleus. A small amount of terminal labeling was found in the lateral cerebellar nucleus, the tangential nucleus, the prepositus hypoglossi, and the lateral vestibular nucleus pars ventralis.     

Location of brain stem neurons projecting to the oculomotor nucleus in the cat

Horseradish peroxidase was injected into the oculomotor nucleus of 11 adult cats and the animals were killed after 48 h. In 7 cats satisfactory labeling occurred in neurons in the superior, medial, and lateral vestibular nuclei, the abducens nucleus, the infracerebellar nucleus, nucleus praepositus hypoglossi, and nucleus interpositus. These retrograde studies confirmed the major vestibulo-ocular pathways shown by anterograde degeneration methods and demonstrated additional projections to the third nerve nucleus which may be activated by peripheral vestibular input.     

Vestibulofugal projections to the lateral reticular nucleus of the cat medulla

Certain amount of neurons in vestibular nuclei were labelled after horseradish peroxidase injection in the medullar lateral reticular nucleus of cat. Such projections were strictly homolateral and formed by small and medium-size neurons localized mainly in the Deiters nucleus; their number was, probably, much less in comparison with the number of vestibulo-spinal units. Functional role of vestibular projections to the lateral reticular nucleus in the motor activity control is discussed.     

Vestibular afferents of the inferior olive and the vestibulo-olivo-cerebellar climbing fiber pathway to the flocculus in the cat

The projection of the vestibular nuclei to the inferior olive was investigated by means of anterograde transport of tritiated leucine. 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. At the contralateral side termination in the dorsomedial cell column and the medial accessory olive was found after injections in the nucleus vestibularis superior and group Y. The ventrolateral outgrowth and different parts of the principal olive also received afferents from these two nuclei and also from ventral parts of the lateral cerebellar nucleus. The dorsal cap was labeled exclusively from the contralateral nucleus prepositus hypoglossi. The termination in the inferior olive of the vestibular afferents is compared with the projection from a number of pretectal nuclei. Furthermore the consequences of the divergence and convergence of both types of projections at the level of the inferior olive is discussed in relation to the subsequent climbing fiber projection to the flocculus.     

The interconnection between the vestibular nuclei and the nodulus: a study of reciprocity

The reciprocal connections between the nodulus and the vestibular and perihypoglossal nuclei in the cat have been studied by anterograde and retrograde transport after implants of crystalline wheatgerm agglutinin-horseradish peroxidase complex (WGA-HRP) restricted to one or two nodular folia. The findings supplement the previous study by Epema et al. (Neurosci. Lett., 1985, 57: 273-278), who injected WGA-HRP into the vestibular nuclei. In that study, details concerning the nodular origin and termination of the fibres within the reciprocal connections were given; in the present study, details are given concerning the origin and termination of the fibres within the vestibular and perihypoglossal nuclei. Our observations give evidence that the nodulovestibular fibres are distributed to a somewhat larger area than that projecting back to the nodulus. The distribution of the labelled cells and fibres is shown in Fig. 2. Of the 4 main nuclei, it is only the lateral vestibular nucleus which is devoid of a reciprocal connection with the nodulus, while only groups x and z of the minor cell groups are found to have such projections. Of the perihypoglossal nuclei, it is only the nucleus praepositus hypoglossi which appears to be interconnected with the nodulus.     

On the projections from the vestibular and perihypoglossal nuclei to the spinal trigeminal and lateral reticular nuclei in the cat

The projection from the vestibular and perihypoglossal nuclei to the spinal trigeminal and lateral reticular nuclei has been studied in cats where the wheat germ agglutinin-horseradish peroxidase complex has been used as a retrograde tracer. All injections were made at the level of the caudal pole of the inferior olive. The medial and descending vestibular, and the perihypoglossal nuclei were found to project to the spinal trigeminal nucleus. The projection to the lateral reticular nucleus reaches its medial-most part only, and originates in the lateral vestibular nucleus. The lateral part of the reticular formation also appears to be the target for some vestibular efferent fibres, mainly from the descending vestibular nucleus. The retrogradely labelled cells within the medial and descending vestibular nuclei are of all sizes and distributed throughout their entire territory. Certain observations furthermore indicate that the fibres reaching the lateral reticular nucleus are collaterals only from the vestibulospinal tract. The projections are bilateral. The observations confirm and extend previous observations on the afferent projections to the spinal trigeminal and lateral reticular nuclei.     

Frontal eye field projection to the paramedian pontine reticular formation traced with wheat germ agglutinin in the monkey

Injections of the retrograde tracer [125I]wheat germ agglutinin have been placed in different areas of the paramedian pontine reticular formation (PPRF), a well known premotor center for gaze control. 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 results are compared with previous anatomical investigations and confirm the electrophysiologically demonstrated FEF-PPRF-abducens disynaptic pathway.     

Neuropeptides and γ-Aminobutyric acid in the vestibular nuclei of the rat: an immunohistochemical analysis. I. Distribution

The distributions of substance P, Leu-enkephalin and γ-aminobutyric acid (GABA) containing structures in the rat vestibular nuclei were investigated by means of an indirect immunofluorescent method using specific antisera to substance P, Leu-enkephalin and glutamic acid decar☐ylase (GAD), respectively.Numerous positive neurons and fibers containing these three substances were found in the medical vestibular nucleus. Most of them were situated in the caudal part of the nucleus and those in the rostral part were concentrated dorsally. In the descending vestibular nucleus, a large number of substance P, Leu-enkephalin and GAD containing neurons were evenly distributed among longitudinally directing fiber bundles. A number of positive fibers with these substances were also observed. The lateral vestibular nucleus contained numerous coarse GAD-immunoreactive fibers surrounding Deiters' neurons, while substance P-immunoreactive and Leu-enkephalin-immunoreactive fibers were rather poorly distributed in this nucleus as well as in the superior vestibular nucleus.     

Organization of the coeruleo-vestibular pathway in rats, rabbits, and monkeys

Inputs from locus coeruleus (LC) appear to be important for altering sensorimotor responses in situations requiring increase vigilance or alertness. This study documents the organization of coeruleo-vestibular pathways in rats, rabbits and monkeys. A lateral descending noradrenergic bundle (LDB) projects from LC to the superior vestibular nucleus (SVN) and rostral lateral vestibular nucleus (LVN). A medial descending noradrenergic bundle (MDB) projects from LC to LVN, the medial vestibular nucleus (MVN), group y and rostral nucleus prepositus hypoglossi (rNPH). There is a characteristic, specific pattern of innervation of vestibular nuclear regions across the three species. A quantitative analysis revealed four distinct innervation density levels (minimal, low, intermediate and high) across the vestibular nuclei. The densest plexuses of noradrenergic fibers were observed in the SVN and LVN. Less dense innervation was observed in the MVN, and minimal innervation was observed in the inferior vestibular nucleus (IVN). In monkeys and rabbits, rostral MVN contained a higher innervation density than the rat MVN. In monkeys, the rNPH also contained a dense plexus of fibers. Selective destruction of terminal LC projections (distal axons and terminals) by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) resulted in a dramatic reduction of immunoreactive fibers within the vestibular nuclear complex of rats, suggesting that the source of these immunoreactive fibers is LC. Retrograde tracer injections into the vestibular nuclei resulted in labeled cells in the ipsilateral, caudal LC and adjacent nucleus subcoeruleus. It is hypothesized that the regional differences in noradrenergic innervation are a substrate for differentially altering vestibulo-ocular and vestibulo-spinal responses during changes in alertness or vigilance.     

Subcortical projections to the centromedian and parafascicular thalamic nuclei in the cat

The primary objective of this study is to identify the totality of input to the centromedian and parafascicular (CM-Pf) thalamic nuclear complex. The subcortical projections upon the CM-Pf complex were studied in the cat with three different retrograde tracers. The tracers used were unconjugated horseradish peroxidase (HRP), horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), and rhodamine-labeled fluorescent latex microspheres (RFM). Numerous subcortical structures or substructures contained labeled neurons with all three tracing techniques. These labeled structures included the central nucleus of the amygdala; the entopeduncular nucleus; the globus pallidus; the reticular and ventral lateral geniculate nuclei of the thalamus; parts of the hypothalamus including the dorsal, lateral, and posterior hypothalamic areas and the ventromedial and parvicellular nuclei; the zona incerta and fields of Forel; parts of the substantia nigra including the pars reticularis and pars lateralis, and the retrorubral area; the pretectum; the intermediate and deep layers of the superior colliculus; the periaqueductal gray; the dorsal nucleus of the raphe; portions of the reticular formation, including the mesencephalic, pontis oralis, pontis caudalis, gigantocellularis, ventralis, and lateralis reticular nuclei; the nucleus cuneiformis; the marginal nucleus of the brachium conjunctivum; the locus coeruleus; portions of the trigeminal complex, including the principal sensory and spinal nuclei; portions of the vestibular complex, including the lateral division of the superior nucleus and the medial nucleus; deep cerebellar nuclei, including the medial and lateral cerebellar nuclei; and lamina VII of the cervical spinal cord. Moreover, the WGA-HRP and rhodamine methods (known to be more sensitive than the HRP method) revealed several afferent sources not shown by HRP: the anterior hypothalamic area, ventral tegmental area, lateral division of the superior vestibular nucleus, nucleus interpositus, and the nucleus praepositus hypoglossi. Also, the rhodamine method revealed labeled neurons in laminae V and VI of the cervical spinal cord.     

Brainstem projection of the vestibular nerve in the guinea pig: An HRP (horseradish peroxidase) and WGA-HRP (wheat germ agglutinin-HRP) study

We explored the course and termination of primary vestibular afferent fibers within the brainstem of the guinea pig by means of anterograde axonal transport of horseradish peroxidase (WGA-HRP). Primary vestibular afferent fibers distribute within the entire vestibular nuclear complex, with the exception of the dorsal part of the lateral vestibular nucleus. The superior vestibular nucleus is characterized by the concentration of terminals within its central part. Although terminal labeling is weaker within the periphery, no area completely lacks primary input. The lateral vestibular nucleus can be divided into a ventral and a dorsal part; within the ventral part small and giant cells receive primary afferent fibers, whereas no significant terminal labeling occurs in the dorsal part. The medial vestibular nucleus shows the most uniform labeling, although the lateral part of its rostral third has a few more terminals than the medial half. Primary projection to the descending vestibular nucleus is widespread, although in its rostrodorsal part it is less impressive. Of the small cell groups commonly associated with the vestibular nuclear complex, only group y receives abundant primary input. Whereas group z completely lacks labeled fibers as well as terminals, single primary axons can be observed passing groups x and f. However, no terminals can be found within the borders of these two cell groups. Scanty projections can be detected within the prepositus hypoglossi nucleus, as well as within the external cuneate nucleus, the cochlear nucleus, the abducent nucleus, and parts of the reticular formation.     

Distribution of zebrin-immunoreactive Purkinje cell terminals in the cerebellar and vestibular nuclei of birds

Zebrin II (aldolase C) is expressed in a subset of Purkinje cells in the mammalian and avian cerebella such that there is a characteristic parasagittal organization of zebrin-immunopositive stripes alternating with zebrin-immunonegative stripes. Zebrin is expressed not only in the soma and dendrites of Purkinje cells but also in their axonal terminals. Here we describe the distribution of zebrin immunoreactivity in both the vestibular and the cerebellar nuclei of pigeons (Columba livia) and hummingbirds (Calypte anna, Selasphorus rufus). In the medial cerebellar nucleus, zebrin-positive labeling was particularly heavy in the “shell,” whereas the “core” was zebrin negative. In the lateral cerebellar nucleus, labeling was not as heavy, but a positive shell and negative core were also observed. In the vestibular nuclear complex, zebrin-positive terminal labeling was heavy in the dorsolateral vestibular nucleus and the lateral margin of the superior vestibular nucleus. The central and medial regions of the superior nucleus were generally zebrin negative. Labeling was moderate to heavy in the medial vestibular nucleus, particulary the rostral half of the parvocellular subnucleus. A moderate amount of zebrin-positive labeling was present in the descending vestibular nucleus: this was heaviest laterally, and the central region was generally zebrin negative. Zebrin-positive terminals were also observed in the the cerebellovestibular process, prepositus hypoglossi, and lateral tangential nucleus. We discuss our findings in light of similar studies in rats and with respect to the corticonuclear projections to the cerebellar nuclei and the functional connections of the vestibulocerebellum with the vestibular nuclei.     

Neuropeptides and gamma-aminobutyric acid in the vestibular nuclei of the rat: an immunohistochemical analysis. I. Distribution

The distribution of substance P, Leu-enkephalin and gamma-aminobutyric acid (GABA) containing structures in the rat vestibular nuclei were investigated by means of an indirect immunofluorescent method using specific antisera to substance P, Leu-enkephalin and glutamic acid decarboxylase (GAD), respectively. Numerous positive neurons and fibers containing these three substances were found in the medial vestibular nucleus. Most of them were situated in the caudal part of the nucleus and those in the rostral part were concentrated dorsally. In the descending vestibular nucleus, a large number of substance P, Leu-enkephalin and GAD containing neurons were evenly distributed among longitudinally directing fiber bundles. A number of positive fibers with these substances were also observed. The lateral vestibular nucleus contained numerous coarse GAD-immunoreactive fibers surrounding Deiters' neurons, while substance P-immunoreactive and Leu-enkephalin-immunoreactive fibers were rather poorly distributed in this nucleus as well as in the superior vestibular nucleus.     

Zonal organization of the vestibulocerebellum in pigeons (Columba livia): II. Projections of the rotation zones of the flocculus

Previous neurophysiologic research in birds and mammals has shown that there are two types of Purkinje cells in the flocculus. The first type shows maximal modulation in response to rotational optokinetic stimulation about the vertical axis (rVA neurons). The second type shows maximal modulation in response to rotational optokinetic stimulation about a horizontal axis oriented 45 degrees to contralateral azimuth (rH45c neurons). In pigeons, the rVA and rH45c are organized into four alternating parasagittal zones. In this study we investigated the projections of Purkinje cells in the rVA and rH45c zones by using the anterograde tracers biotinylated dextran amine and cholera toxin subunit B. After iontophoretic injections of tracers into the rH45c zones, heavy anterograde labeling was found in the infracerebellar nucleus and the medial margin of the superior vestibular nucleus. Some labeling was also consistently observed in the lateral cerebellar nucleus and the dorsolateral vestibular nucleus. 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. Less labeling was seen in the tangential nucleus, the dorsolateral vestibular nucleus, and the lateral vestibular nucleus, pars ventralis. These results are compared and contrasted with findings in mammalian species.