Visualization of outgrowing axons of grafted neurons by anterograde labelling with Phaseolus vulgaris leucoagglutinin in the motor cortex of the rat

Fetal cerebral cortical tissue was transplanted into an aspirated lesion cavity made in the sensorimotor cortex of adult rats. Ten weeks after grafting, outgrowing fibers from the graft were visualized by an anterograde tracing technique using Phaseolus vulgaris leucoagglutinin (PHA-L). It was demonstrated that the efferent fibers grew into the neighboring host cortical tissue, the corpus callosum and in some cases approached caudate/putamen. Characteristic axon arborization with abundant boutons were found in the host cortical tissue, but only in close vicinity to the grafts. It is concluded that the PHA-L anterograde tracing technique can be a useful tool to assess the degree of anatomical integration of the transplants into the host tissue.     

Projections of the dorsal raphe nucleus to the brainstem: PHA-L analysis in the rat

Early studies that used older tracing techniques reported exceedingly few projections from the dorsal raphe nucleus (DR) to the brainstem. The present report examined DR projections to the brainstem by use of the anterograde anatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L). DR fibers were found to terminate relatively substantially in several structures of the midbrain, pons, and medulla. The following pontine and midbrain nuclei receive moderate to dense projections from the DR: pontomesencephalic central gray, mesencephalic reticular formation, pedunculopontine tegmental nucleus, medial and lateral parabrachial nuclei, nucleus pontis oralis, nucleus pontis caudalis, locus coeruleus, laterodorsal tegmental nucleus, and raphe nuclei, including the central linear nucleus, median raphe nucleus, and raphe pontis. The following nuclei of the medulla receive moderately dense projections from the DR: nucleus gigantocellularis, nucleus raphe magnus, nucleus raphe obscurus, facial nucleus, nucleus gigantocellularis-pars alpha, and the rostral ventrolateral medullary area. DR fibers project lightly to nucleus cuneiformis, nucleus prepositus hypoglossi, nucleus paragigantocellularis, nucleus reticularis ventralis, and hypoglossal nucleus. Some differences were observed in projections from rostral and caudal parts of the DR. The major difference was that fibers from the rostral DR distribute more widely and heavily than do those from the caudal DR to structures of the medulla, including raphe magnus and obscurus, nucleus gigantocellularis-pars alpha, nucleus paragigantocellularis, facial nucleus, and the rostral ventrolateral medullary area. A role for the dorsal raphe nucleus in several brainstem controlled functions is discussed, including REM sleep and its events, nociception, and sensory motor control. © Wiley-Liss, Inc.     

The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation

Stimulation of the vagus nerve produces antiepileptic effects. This is used clinically to treat drug-refractory epilepsies. The mechanisms responsible for these effects depend on the activation of vagal afferents reaching the nucleus of the solitary tract. This review focuses on the neuroanatomy of the nucleus of the solitary tract and its relation with the nucleus locus coeruleus as a preferential anatomical substrate in producing antiepileptic effects. In fact, following the transient or permanent inactivation of locus coeruleus neurons, some antiepileptic effects of vagus nerve stimulation are lost. The activation of locus coeruleus per se is known to limit the spread of a seizure and the duration of a variety of seizure types. This is due to the fine chemical neuroanatomy of norepinephrine pathways that arise from the locus coeruleus, which produce widespread changes in cortical areas. These changes may be sustained by norepinephrine alone, or in combination with its co-transmitters. In addition, vagus nerve stimulation may prevent seizures by activating the serotonin-containing dorsal raphe neurons.     

Descending projections of the basal forebrain in the rat demonstrated by the anterograde neural tracer Phaseolus vulgaris leucoagglutinin (PHA-L)

Descending pathways from the mediobasal forebrain were studied in the rat by injecting anterograde axonal tracer Phaseolus vulgaris leucoagglutinin into the substantia innominata and diagonal band of Broca. From both areas, positive fibers which varied in density were observed in the mediodorsal and ventral parts of the ventroposterior and ventromedial thalamic nuclei, the lateral habenula, the stria medullaris, the lateral hypothalamus and the ventral tegmental area. This descending complex appeared predominantly course through the medial forebrain bundle from which positive fibers ramified into the fasciculus thalamicus to distribute in the thalamic nuclei. A minor descending pathway through the stria medullaris was also noted which terminated in the lateral habenula and the mediodorsal thalamic nucleus. An obvious difference in terminal distribution in the medial habenula, mediodorsal thalamic nucleus and pons could be observed following substantia innominata or diagonal band injection.     

Descending projections of the posterior nucleus of the hypothalamus: Phaseolus vulgaris leucoagglutinin analysis in the rat

No previous report in any species has systematically examined the descending projections of the posterior nucleus of the hypothalamus (PH). The present report describes the descending projections of the PH in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin. PH fibers mainly descend to the brainstem through two routes: dorsally, within the central tegmental tract; and ventromedially, within the mammillo-tegmental tract and its caudal extension, ventral reticulo-tegmental tracts. PH fibers were found to distribute densely to several nuclei of the brainstem. They are (from rostral to caudal) 1) lateral/ventrolateral regions of the diencephalo-mesopontine periaqueductal gray (PAG); 2) the peripeduncular nucleus; 3) discrete nuclei of pontomesencephalic central gray (dorsal raphe nucleus, laterodorsal tegmental nucleus, and Barrington's nucleus); 4) the longitudinal extent of the central core of the mesencephalic through medullary reticular formation (RF); 5) the ventromedial medulla (nucleus gigantocellularis pars alpha, nucleus raphe magnus, and nucleus raphe pallidus); 6) the ventrolateral medulla (nucleus reticularis parvocellularis and the rostral ventrolateral medullary region); and 7) the inferior olivary nucleus. PH fibers originating from the caudal PH distribute much more heavily than those from the rostral PH to the lower brainstem. The PH has been linked to the control of several important functions, including respiration, cardiovascular activity, locomotion, antinociception, and arousal/wakefulness. It is likely that descending PH projections, particularly those to the PAG, the pontomesencephalic RF, Barrington's nucleus, and parts of the ventromedial and ventrolateral medulla, serve a role in a PH modulation of complex behaviors involving an integration of respiratory, visceromotor, and somatomotor activity. © 1996 Wiley-Liss, Inc.     

Organization of the projections from the trigeminal brainstem complex to the superior colliculus in the rat and hamster: anterograde tracing with Phaseolus vulgaris leucoagglutinin and intra-axonal injection

Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and intra-axonal recording and injection techniques were employed to describe the projection from the trigeminal (V) brainstem complex to the deep laminae of the superior colliculus (SC) in the hamster and the rat. The organization of these projections was the same in the two species. Deposits of PHA-L into V nucleus principalis (PrV) produced labelled axons and boutonlike swellings in the lower stratum griseum intermediale (SGI) and upper stratum album intermedium (SAI) in the SC bilaterally. Plots of boutonlike swellings indicated that the terminals of this projection were arrayed in clusters. Nucleus principalis also projected to the stratum griseum profundum (SGP) and stratum album profundum (SAP). This deeper projection did not terminate in clusters and it was most prominent in the lateral SC. The ipsilateral PrV-SC projection appeared to arise mainly from axons that recrossed the midline at the level of the SC commissure. Reconstruction of individual PHA-L labelled fibers demonstrated that single axons gave rise to terminals on both sides of the midline. Deposits of PHA-L into V subnucleus interpolaris (SpI) yielded results that were identical to those obtained with PrV injections with one exception: none of these deposits produced any labelled terminals in the ipsilateral SC. Deposits of PHA-L into V subnucleus caudalis (SpC) produced only sparse labelling in SC. Most labelled swellings were located in the SGP and SAP and they were visible only in the SC contralateral to the PHA-L injection site. Single axons arising from cells in SpI were recorded and injected with horseradish peroxidase (HRP) in the hamster's SC. These fibers all responded to stimulation of multiple mystacial vibrissae and gave rise to 2-5 clusters of bouton-like swellings in the lower SGI and upper SAI.     

Organization of the projections from the pericruciate cortex to the pontomedullary brainstem of the cat: A study using the anterograde tracer Phaseolus vulgaris-leucoagglutinin

The anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) was used to study the distribution and density of the projections that originate from four identified subdivisions of the pericruciate cortex (namely, the forelimb and hind limb representations of area 4, area 6aβ, and area 6aγ) and that terminate in the pontomedullary brainstem in the cat. Injections of PHA-L in all areas of the pericruciate cortex labelled numerous fibers and their terminal swellings in the brainstem. The major target regions of all four cortical areas were the pontine nuclei and the pontomedullary reticular formation (PMRF). Injections into both the forelimb and hind limb representations of area 4 and into area 6aβ resulted in a dense pattern of terminal labelling in restricted regions of the medial and lateral parts of the ipsilateral pontine nuclei. The labelling following the area 6aβ injection was spatially distinct from that seen following the area 4 injections. Injections into the forelimb representation of area 4 as well as into area 6aβ and 6aγ resulted in the labelling of numerous terminal swellings bilaterally in the PMRF; in contrast, there were few labelled terminal swellings in the PMRF following injections into the hind limb representation of area 4. Terminal swellings on individual corticoreticular fibers were far less densely aggregated than those in the pontine nuclei. The dense pattern of innervation to restricted regions of the pontine nuclei supports previous suggestions that the corticopontine projections retain a high degree of topographical specificity that could be used in the control of discrete voluntary movements. In contrast, the more diffuse pattern of the projections to the PMRF may facilitate the selection and activation of the complex postural patterns that accompany voluntary movement. J. Comp. Neurol. 389:617–641, 1997. © 1997 Wiley-Liss, Inc.     

Amygdalonigral pathway: an anterograde study in the rat with Phaseolus vulgaris leucoagglutinin (PHA-L)

The projection from the central nucleus of the amygdala to the substantia nigra was labeled by injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into different subregions of the nucleus. A sparse projection of labeled bouton-like swellings was observed in the rostral, medial substantia nigra pars compacta and ventral tegmental area from all subregions of the central nucleus of the amygdala that were injected. A dense projection of labeled axons and bouton-like swellings was observed in the lateral part of the substantia nigra pars compacta and pars lateralis when the injection site included the dorsal and rostral central nucleus. Heavy labeling was also seen in the lateral retrorubral field in these cases. In no instances were labeled terminals observed in the substantia nigra pars reticulata. The same pattern of labeling in the lateral substantia nigra and retrorubral field was seen after injections rostral to the central nucleus or dorsal and medial to it in the sublenticular region. The results suggest that the amygdalonigral pathway contributes to the innervation of extensive areas of the substantia nigra pars compacta. The major component of the pathway, however, projects only to a subregion of the substantia nigra. The origin of this pathway is confined to a discrete region of the dorsal central nucleus of the amygdala but extends rostrally into an area that is part of the "extended amygdala."     

The central amygdaloid nucleus innervation of the dorsal vagal complex in rat: a Phaseolus vulgaris leucoagglutinin lectin anterograde tracing study

The central nucleus of amygdala (Ce) participates in expression of autonomic responses associated with fear or stress-related behaviors. The Ce can alter autonomic activity through its direct projection to the dorsal vagal complex [i.e., nucleus of the solitary tract (nTS) and the dorsal vagal nucleus]. In order to more precisely define the anatomical organization of the neurons within the Ce and their terminal fields within the dorsal vagal complex, the Phaseolus vulgaris leucoagglutinin lectin (PHA-L) anterograde tracing method was employed in rats. In cases where injections of PHA-L were centered within the medial Ce, dense axon terminal labeling was observed within the medial nTS at rostral levels. Terminal boutons were also observed within the ventral part of the lateral nTS, the dorsal vagal nucleus and contralateral medial nTS. At and just rostral to the obex, numerous axonal boutons were seen within the medial and commissural parts of the nTS and adjacent parts of the dorsal vagal nucleus. Contralateral axon terminal labeling was present within the medial and commissural parts of the nTS. Caudal to the obex, PHA-L immunoreactive boutons were concentrated bilaterally within the medial and commissural nTS and dorsal vagal nucleus. In cases where injections of PHA-L were centered within the lateral Ce moderate axon terminal labeling was observed throughout the rostrocaudal extent of the medial and commissural part of the nTS. Very few PHA-L immunoreactive terminals were observed within the ventral part of the lateral nTS, dorsal vagal nucleus and contralateral medial nTS. The results demonstrate that the medial Ce projects bilaterally to the medial and commissural subnuclei of the nTS and the dorsal vagal nucleus. The lateral Ce projects mainly to the ipsilateral medial and commissural nTS. Thus, both the medial and lateral Ce can directly influence regions of the nTS where peripheral cardiovascular, cardiopulmonary and gastric afferents terminate. The medial Ce can also directly affect vagal nerve outflow through its projection to neurons within the dorsal motor nucleus.     

Origins and terminations of bulbospinal axons that contain serotonin and either enkephalin or substance-P in the North American opossum.

We have shown previously that some enkephalin, substance-P, and serotoninergic neurons in the medullary raphe and adjacent reticular formation project to the spinal cord in the opossum. In the present study we have combined the retrograde transport of True Blue and immunofluorescence histochemistry to determine whether methionine enkephalin or substance-P containing bulbospinal neurons are serotoninergic. Furthermore, we have used the same immunofluorescence protocol to determine whether spinal axons contain the same substances. Neurons that immunostained for both enkephalin and serotonin were observed in many brainstem nuclei. However, those that projected to the spinal cord were limited to the nuclei raphe magnus and obscurus, and the ventral part of nucleus reticularis gigantocellularis, pars ventralis. Neurons that immunostained for both substance P and serotonin were fewer in number, but some of the ones in the above nuclei and within the nucleus raphe pallidus, projected to the spinal cord. Spinal axons exhibiting both enkephalin- and serotonin-like immunoreactivity were observed in the superficial laminae of the dorsal horn, lamina X, and the intermediolateral cell column, whereas those showing both substance-P and serotonin-like immunoreactivity were seen primarily in lamina X, the intermediolateral cell column, and the ventral horn. Some of the axons in the ventral horn were in close apposition to presumed motoneurons. Comparison of the above results with those obtained from previous studies of bulbospinal projections has allowed us to infer the origins of axons that innervate different spinal targets.     

Distribution of primary vestibular fibers in the brainstem and cerebellum of the monkey

Attempts were made to determine the central projections of ganglion cells innervating individual semicircular ducts in the monkey by implanting or injecting tritiated amino acids (leucine and/or proline), or horseradish peroxidase (HRP), selectively into a single ampulla. Central transport via the vestibular ganglion in animals receiving isotope implants or injections fell into three categories: (1) transport from ganglion cells innervating all receptive elements of the labyrinth, (2) transport from ganglion cells innervating the three semicircular ducts, and (3) transport from cells of the inferior vestibular ganglion innervating the posterior semicircular duct. Transneuronal transport of isotope was observed in secondary vestibular fibers in animals where proline was used and survival exceeded 12 days. Transneuronal labeling of secondary auditory fibers was independent of the [³H]amino acid used, and occurred with survivals of 10 or more days. HRP implanted into the ampulla of the lateral semicircular duct in several animals produced retrograde transport to efferent vestibular and cochlear neurons, but did not result in transganglionic labeling of primary vestibular or auditory fibers.Primary vestibular fibers terminate throughout the superior (SVN) and medial vestibular nuclei (MVN). Within SVN, terminals are most pronounced in its central large-celled portion, but extend into peripheral parts of the nucleus, except for a small medial area near its junction with the oral pole of MVN. Primary projections to MVN are homogenously distributed throughout the nucleus excepting a small circular area of sparse terminals along its ventral margin. Primary vestibular afferents terminate mainly in rostral and caudal portions of the inferior vestibular nucleus (IVN), but do not reach cell group ‘f’. Projections to the lateral vestibular nucleus (LVN) are restricted to its ventral part. Primary projections to the accessory vestibular nuclei reach the interstitial nucleus of the vestibular nerve (NIVN) and cell group ‘y’. Fibers project beyond the vestibular nuclei (VN) to terminate ipsilaterally in the accessory cuneate nucleus (ACN), the subtrigeminal lateral reticular nucleus (SLRN), and well-defined portions of the reticular formation (RF). Projections to SVN and MVN are derived primarily from ganglion cells innervating the semicircular ducts, while projections to caudal IVN, cell group ‘y’ and ACN are related mainly to macular portions of the vestibular ganglion. NIVN receives both macular and duct afferents. Posterior duct afferents terminate in medial portions of SVN, in rostrolateral portions of MVN, and in rostral IVN.Transneuronal transport of isotope increases the volume of terminal label in the ipsilateral VN, but not in dorsal LVN, or cell groups ‘f’ or ‘x’. The quality of transneuronal transport in secondary vestibular fibers is dependent upon: (1) survival time, (2) proximity to the VN, and (3) the excitatory or inhibitory nature of the projection.Primary vestibulocerebellar fibers terminate heavily in the ipsilateral nodulus and ventral uvula. Lesser projections reach the flocculus, deep folia of vermal lobules V and VI, and the lingula. Primary vestibulocerebellar projections terminate as mossy fiber rosettes in the granular layer of these cortical areas. No primary vestibular fibers terminate in the primate fastigial nuclei.     

Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat

The projections of the medial preoptic nucleus (MPN) were examined by making injections of the anterogradely transported lectin Phaseolus vulgaris leucoagglutinin (PHA-L) into the MPN and charting the distribution of labeled fibers. The evidence indicates that the MPN projects extensively to widely distributed regions in both the forebrain and brainstem, most of which also supply inputs to the nucleus. An important neuroendocrine role for the MPN is underscored by its extensive projections to almost all parts of the periventricular zone of the hypothalamus, including the anteroventral periventricular, anterior part of the periventricular, paraventricular (PVH), and arcuate nuclei, and a role in autonomic mechanisms is indicated by projections to such regions as the dorsal and lateral parvicellular parts of the PVH, the lateral parabrachial nucleus, and the nucleus of the solitary tract. Other projections of the MPN suggest participation in the initiation of specific motivated behaviors. For example, inputs to two nuclei of the medial zone of the hypothalamus, the ventromedial and dorsomedial nuclei, may be related to the control of reproductive and ingestive behaviors, respectively, although the possible functional significance of a strong projection to the ventral premammillary nucleus is presently unclear. The execution of these behaviors may involve activation of somatomotor regions via projections to the substantia innominata, zona incerta, ventral tegmental area, and pedunculopontine nucleus. Similarly, inputs to other regions that project directly to the spinal cord, such as the periaqueductal gray, the laterodorsal tegmental nucleus, certain medullary raphe nuclei, and the magnocellular reticular nucleus may also be involved in modulating somatic and/or autonomic reflexes. Finally, the MPN may influence a wide variety of physiological mechanisms and behaviors through its massive projections to areas like the ventral part of the lateral septal nucleus, the bed nucleus of the stria terminalis, the lateral hypothalamic area, the supramammillary nucleus, and the ventral tegmental area, all of which have extensive connections with regions along the medial forebrain bundle. Although the PHA-L method does not allow a clear demonstration of possible differential projections from each subdivision of the MPN, our results suggest that each of them does give rise to a unique pattern of outputs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Axonal trajectories and terminations of on- and off-cells in the cat lower brainstem

Two physiologically defined classes of pontomedullary raphe neurons were intracellularly labeled in order to determine the target nuclei of their axonal projections. In the lightly anesthetized cat, cells either increased (on-cells) or decreased (off-cells) their discharge rate during the paw withdrawal reflex evoked by noxious pinch or heat. On- and off-cells were injected with horseradish peroxidase and the initial course of labeled axons through the lower brainstem was reconstructed. On-cell projections to the pontomedullary raphe and medial reticular nuclei were sparse. On-cells projected densely to regions of the lateral reticular formation and the ventrolateral medulla at both rostral and caudal medullary levels. In general, on-cells had few collaterals and spare axonal swellings. In contrast to on-cells, most off-cells had axons that collateralized densely within the brainstem raphe and adjacent reticular formation. Such collaterals were either local, within the neuron's dendritic field, or distant, involving a projection of 1-8 mm. One off-cell had a dense terminal field within the sensory trigeminal complex, a projection that may subserve the inhibition of trigeminal sensory neurons produced by raphe magnus stimulation. Well-labeled off-cells had numerous collaterals and dense regions of axonal swellings. In summary, off-cells terminated densely in the raphe magnus and adjacent reticular formation whereas on-cells projected predominantly to the ventrolateral medulla, a region implicated in autonomic control. Local off-cell collaterals provide an anatomical substrate that would enable off-cells to coordinate the activity of on- and off-cells through synaptic contacts.     

The projection of locus coeruleus neurons to the spinal cord in the rat determined by anterograde tracing combined with immunocytochemistry

Pontospinal noradrenergic neurons located in the A5, A7 and locus coeruleus/subcoeruleus (LC/SC) nuclei are the major source of the noradrenergic innervation of the spinal cord. However, the specific terminations of spinally-projecting noradrenergic neurons located in these nuclei have not been clearly defined. The purpose of the experiments described in this report was to more precisely define the spinal terminations of neurons located in the LC/SC using the anterograde tracer phaseolus vulgaris-leucoagglutinin in combination with dopamine-beta-hydroxylase (D beta H) immunocytochemistry. In addition, the spinal cord regions in which LC/SC neurons terminate was assessed by measuring the reduction in the density of D beta H-immunoreactive axon terminals in specific spinal cord regions after a unilateral electrolytic lesion that included LC/SC neurons. The results of these experiments indicate that the axons of LC neurons are located primarily in the ipsilateral ventral funiculus and terminate most heavily in the medial part of laminae VII and VIII, the motoneuron pool of lamina IX, and lamina X. LC neurons provide a moderately dense innervation of the ventral part of the dorsal horn, but only a very sparse innervation of the superficial dorsal horn. The SC projects ipsilaterally in the ventrolateral funiculus and terminates diffusely in the intermediate and ventral laminae of the spinal cord.     

Ascending and descending projections of the nucleus reticularis gigantocellularis in the cat demonstrated by the anterograde neural tracer, Phaseolus vulgaris leucoagglutinin (PHA-L)

Ascending and descending projections of the nucleus reticularis gigantocellularis (NRGc) were studied in the cat by the anterograde tracer, Phaseolus vulgaris leucoagglutinin. Ascending fibers from the left or the right NRGc coursed through the bilateral medial reticular formation and some of them reached the diencephalon. In the brainstem, PHA-L-labeled fibers and their terminals were observed in the medial reticular formation, the cranial motor nuclei (III, IV, V, VI, VII, XII), the vestibular complex, the LC complex, the raphe nuclei, the periaqueductal gray, the red nucleus, the Edinger-Westphal nucleus and the interstitial nucleus of Cajal. In the diencephalon, they were observed in the dorsal thalamus and the hypothalamic regions. In the caudal medulla, labeled fibers and their terminals were observed in the nucleus prepositus hypoglossi, the nucleus intercalatus and the inferior olive. Descending axons from the NRGc coursed bilaterally through the ventral and ventrolateral funiculi as far caudal as the upper thoracic cord. Single axon collaterals arising from the descending axons gave off terminal fibers to the left or the right gray matter. Their terminals were located in laminae V-X, mainly in laminae VII and VIII. In lamina IX, they were distributed mainly in the medial portion. A few fibers originating from the descending axons ipsilateral to the PHA-L injection side coursed through the anterior or posterior commissure, and ended in laminae VI, VII and VIII. The functional implications of these findings are discussed in relation to the behavioral state control and the generalized motor inhibition.     

Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the higher order processing autonomic nuclei of the lower brainstem

The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB), as well as the intermediate reticular zone (IRZ) represent pivotal subordinate brainstem centres, all of which control autonomic functions. In this study, we investigated the occurrence and severity of the neuronal and glial cytoskeletal pathology in these six brainstem nuclei from 17 individuals with clinically diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP). The association between the severity of the pathology and the duration of the disease was investigated by means of correlation analysis. The brainstem nuclei in all of the PSP cases were affected by the neuronal cytoskeletal pathology, with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB marked involvement, and the LPB mild involvement. In the six nuclear greys studied, glial cells undergo alterations of their cytoskeleton on an irregular basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the severity of the neuronal or glial cytoskeletal pathology showed no correlation with the duration of PSP. In view of their functional role, the neuronal pathology in the nuclei studied offers a possible explanation for the autonomic dysfunctions that eventually develop in the course of PSP.     

A direct neural projection from the intergeniculate leaflet of the lateral geniculate nucleus to the deep pineal gland of the rat, demonstrated with Phaseolus vulgaris leucoagglutinin.

The anterograde tracerPhaseolus vulgaris leucoagglutinin (PHA-L) was injected into different subregions of the rat lateral geniculate nucleus. After a survival for 5–10 days, the rats were fixed by perfusion with 4% paraformaldehyde, whereafter the brains were cut in a cryostat and the tracer was localized by immunohistochemistry. After deposits of PHA-L involving the intergeniculate leaflet, a high number of PHA-L-immunoreactive fibers were observed to project directky into the posterior commissure. From the posterior commissure, some nerve fibers turned dorsally and entered into the deep pineal gland, a part of the pineal complex located in between the posterior and the habenular commissure. A few PHA-L-immunoreactive fibers were observed in the pineal stalk, but no fibers were detected in the superficial pineal gland. In cases where the injections were placed in the dorsal or ventral subnuclei, no immunoreactive nerve fibers were observed to enter the pineal complex. These results indicate that the intergeniculate leaflet of the lateral geniculate nucleus, a nucleus considered to be involved in circadian rhythmicity, might influence the pineal gland, via a neural projection to the rostral part of the pineal complex.