Organization of primate internal pallidum as revealed by fluorescent retrograde tracing of its efferent projections.
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The cellular origin and degree of collateralization of the pallidointralaminar and pallidonigral projections in squirrel monkey (Saimiri sciureus) were studied using Evans blue (EB) and a mixture of DAPI-Primuline (DP) as fluorescent retrograde tracers. In a first series of experiments EB was injected into the VA/VL thalamic nuclei whereas DP was delivered into the CM/Pf complex. After these injections numerous EB-labeled cells were scattered throughout the central 'motor' zone of the internal segment of the globus pallidus (GPi), compared to a smaller number of DP-positive neurons forming two small but distinct clusters in central GPi. The majority of the neurons within these two clusters were double-labeled. In addition, EB-labeled cells were disclosed in the lateral two-thirds of substantia nigra pars reticulata (SNr), whereas DP-positive neurons occurred in a wide variety of structures including the nucleus reticularis thalami, the SNr, the periaqueductal gray, the superior colliculus, the midbrain raphe nuclei, the pedunculopontine nucleus (TPP) area (bilaterally), and the locus coeruleus. In a second series of experiments, EB was injected into the CM/Pf complex whereas DP was delivered into the TPP area of the midbrain tegmentum. After these injections two small clusters of EB-labeled cells and a larger number of more uniformly distributed DP-positive cells occurred in the core of GPi. The cell clusters were similar in size and location to those observed after VA/VL-CM/Pf injection, but contained only a minority of double-labeled neurons. The distribution of non-pallidal cells projecting to CM/Pf complex was similar to that reported above, whereas retrogradely labeled cells resulting from TPP injection were disclosed in the paraventricular hypothalamic nucleus, the central amygdaloid nucleus, the preoptico-hypothalamic complex, the lateral habenula, the ventral tegmental area, and the SNr where some double-labeled cells were present. In a third series of experiments DP alone was injected into the entire substantia nigra (SN), involving both pars compacta and pars reticulata. The SN injection produced retrograde cell labeling in numerous structures such as the striatum, the rostral intralaminar nuclei, the subthalamic nucleus, the TPP area (bilaterally), the dorsal raphe nucleus and the locus coeruleus. At pallidal levels, a moderate number of DP-labeled cells occurred within the dorsal half of the external segment of the globus pallidus (GPe), whereas the GPi was virtually devoid of labeled neurons. The GPi appeared nevertheless surrounded ventromedially by numerous large-sized DP-positive cells belonging to the substantia innominata.(ABSTRACT TRUNCATED AT 400 WORDS)
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The cellular origin and degree of collateralization of the subcortical afferents to the caudate nucleus and the putamen in squirrel monkeys (Saimiri sciureus) were studied using the following combinations of fluorescent retrograde tracers: Evans blue and DAPI-Primuline, Fast blue and Nuclear yellow, True blue and Nuclear yellow. After the injections, cells containing the tracer delivered in caudate nucleus (caudate-labeled cells) and others labeled with the complementary tracer injected in putamen (putamen-labeled cells) occur in large number in intralaminar nuclei, substantia nigra pars compacta, midbrain raphe nuclei and central midbrain tegmentum. In addition, a small to moderate number of putamen-labeled cells is found in external pallidum, pulvinar and laterodorsal thalamic nuclei, and basolateral amygdaloid nucleus, whereas some caudate and putamen-labeled cells are scattered in ventral tegmental area and locus coeruleus. However, ver few double-labeled cells are present in all these structures. In rostral intralaminar nuclei, the labeled cells are not confined to the know cytoarchitectonic boundaries of the nuclei but impinge slightly upon ventrolateral and mediodorsal nuclei. At this level, the caudate-labeled cells lie more dorsally and medially relative to putamen-labeled cells, but a high degree of intermingling exists and some double-labeled cells occur particularly in nucleus centralis lateralis. In caudal intralaminar nuclei, caudate-labeled cells are strictly confined to parafascicular nucleus and putamen-labeled cells present only in centre median, without any overlap between the two neuronal populations. In substantia nigra pars compacta, clusters of caudate-labeled cells are closely intermingled with clusters of putamen-labeled cells according to a complex mosaic-like pattern that varies along the rostrocaudal extent of the structure. Overall, however, caudate-labeled cells predominate rostrodorsally and putamen-labeled cells are more abundant caudoventrally in substantia nigra pars compacta, with only a few double-labeled cells. Some caudate and putamen-labeled cells are also scattered in contralateral substantia nigra pars compacta. In dorsal raphe nucleus, putamen labeled cells tend to occupy a more lateral position relative to caudate-labeled cells, with again very few double-labeled neurons. The caudate and putamen-labeled cells are less numerous and more closely intermingled in nucleus centralis superior. Numerous striatal afferent cells are also found bilaterally in the peribrachial region of midbrain tegmentum, comprising the pedunculopontine nucleus area.(ABSTRACT TRUNCATED AT 400 WORDS)
The cellular origin and degree of collateralization of the efferent projections of the substantia nigra pars reticulata (SNr) in the squirrel monkey (Saimiri sciureus) were studied using the following combinations of fluorescent retrograde tracers: Evans blue and DAPI-Primuline, Fast blue and Nuclear yellow, True blue and Nuclear yellow. In a first series of experiments one tracer was injected in the ventral anterior (VA) and ventral lateral (VL) thalamic nuclei, and the complementary tracer was delivered in the peribrachial area of midbrain tegmentum. After thalamo-tegmental injections numerous nigrothalamic neurons occur in clusters, particularly in rostrolateral part of SNr, whereas the nigrotegmental neurons prevail in caudomedial segment of SNr. However, a significant overlap exists between these two populations. The nigrothalamic and nigrotegmental neurons are present in about equal number in SNr with as much as 60% of these neurons being double-labeled. In a second series of experiments injections were made concomitantly in VA/VL nuclei and in superior colliculus. After thalamo-collicular injections the nigrothalamic neurons are found in larger number than the nigrocollicular neurons which are mostly confined to the middle third of SNr. About 15-20% of all SNr positive neurons are double-labeled, although this proportion climbs to 30-40% in certain sections taken through the middle third of SNr. Finally, injections were made concomittantly in superior colliculus and in midbrain tegmentum. In contrast to the findings obtained after thalamo-tegmental and thalamo-collicular injections, only about 10% of SNr neurons appear to be double-labeled after colliculo-tegmental injections. All injections made in present study have produced retrograde cell labeling in contralateral SNr. However, by far the largest number of contralateral labeled neurons is found after superior colliculus injection. These findings reveal that the SNr neurons in primate, as those in rat and cat, display a high degree of axonal branching. As such, the output organization of SNr appears to differ markedly from that of the substantia nigra pars compacta, but is remarkably similar to that of the internal pallidum which is the other major output structure of the basal ganglia.
Four cases of muco-epidermoid carcinoma of the conjunctiva are described, with an electron microscopy study in one case. Three patients were over 70 years and the fourth one 39 years old. In all cases, the tumor was primarily located close to the limbus and appeared as a quiescent corneoscleral ulcer or as a diffuse limbal thickening. Histologically, they showed an admixture of epidermoid and mucus secreting cells on alcian blue staining, and this was confirmed by electron microscopy. These tumors appear to be locally aggressive and rapidly recurring, and they invade the intra-ocular structures and/or orbit. One patient died 6 years after the onset of the disease. Prognosis is therefore poor and the lesion requires early treatment by wide local excision and a strict follow up for early detection of any recurrence.
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The exact cellular origin and the degree of collateralization of the major efferent projections from the internal segment of globus pallidus (GPi) in squirrel monkey (Saimiri sciureus) were studied using Evans blue (EB) and a mixture of DAPI-primuline (DP) as retrograde fluorescent tracers. After the concomitant injection of EB in VA/VL thalamic nuclei and of DP in habenula on the same side, numerous EB-labeled cells were found in the central portion of GPi compared to a much smaller number of DP-labeled neurons mostly encountered at the periphery of GPi. Only very few double-labeled cells were visualized in these experiments indicating that the pallidohabenular and pallidothalamic pathways arise largely from two different cell populations, each having a preferential distribution in GPi. On the other hand, a multitude of both EB- and DP-labeled cells occurred in the central portion of GPi after the concomitant injection of EB in VA/VL nuclei and of DP in nucleus tegmenti pedunculopontinus of the midbrain tegmentum. Although the EB-labeled cells tend to be more abundant in the dorsolateral half, and the DP-labeled cells more numerous in the ventromedial half of GPi, about 70-75% of the cells in the core of GPi were double-labeled in such a case. This indicates that the pallidothalamic and pallidotegmental fibers arise largely from the same neurons in the core of GPi. A number of DP-labeled cells was also found in the contralateral GPi revealing that the pallidotegmental pathway is partly (15-20%) crossed. In addition, numerous DP-labeled cells (projecting to brain stem) occurred in the medial two-thirds of the substantia nigra pars reticulata (SNr), whereas EB-labeled cells (projecting to the thalamus) abounded in the lateral third of SNr. A small number of double-labeled SNr cells were also encountered after thalamus-midbrain injection. These findings suggest that in regard to its output elements, the primate GPi is organized according to a complex pattern consisting of: (1) a central 'motor' zone where most neurons send axonal branches to both thalamus and midbrain; and (2) a peripheral 'limbic' zone which encroaches largely upon the lateral hypothalamus and whose cells project only to habenula. These two pallidal zones are furthermore embedded in a peripallidal neuronal network composed of large acetylcholinesterase-containing cells related to nucleus basalis and projecting diffusely to neocortex.
The zona incerta (ZI) and lateral hypothalamic afferents to the midbrain reticular formation (MRF) of cat were investigated with the horseradish peroxidase (HRP) technique and by using antidromic identification in experiments on chronically implanted, behaving preparations. Following HRP injections restricted to the MRF territory (nucleus cuneiformis and central tegmental field), the largest number of retrogradely labeled cells appeared in the medial third of the ipsilateral ZI. Labeling extended medially to the adjacent lateral hypothalamus. The number of positive elements gradually diminished towards the lateral extremity of the ZI and continuing reticularis thalamic nucleus. Ventral lateral geniculate neurons were consistently labeled. No positive elements were found in ventrobasal, pulvinar-lateralis posterior and ventralis lateralis thalamic nuclei. The MRF-evoked antidromic invasion of ZI cells occurred with a sharp mode between 0.5 and 0.75 ms (median latency of the whole sample: 0.6 ms). The conduction velocity of the ZI leads to MRF axons is twice as high as the values found in the reciprocal MRF leads to ZI projection. In addition to the antidromically elicited discharges, MRF stimulated resulted in short-latency synaptic excitation, sometimes following the antidromic invasion of the same neuron. The difference between the discharge rates of ZI neurons during EEG-desynchronized and EEG-synchronized behavioral states was not significant. A statistically significant increase in firing rates was found in ZI neurons during waking periods with movements compared to quiet, motionless epochs of waking. The possible involvement of caudally projecting ZI cells in the preparation of postural and/or phasic motor functions is discussed.
The topographical distribution and morphological characteristics of neurons containing acetylcholinesterase (AChE, EC 3.1.1.7) in the basal forebrain of the cat were studied by means of the Butcher's pharmaco-histochemical technique involving staining for AChE at various times after the administration of di-isopropylfluorophosphate (DFP). This method allows a clear visualization of numerous AChE-producing neurons in olfactory tubercle, medial septal-diagonal band area, hypothalamus and basal ganglia. In olfactory tubercle the AChE neurons abound in the deep polymorph layer where they form several types of cell clusters topographically related to the islands of Calleja. The AChE neurons in medial septal nucleus appear morphologically similar to those in nucleus of the diagonal band. As a whole, the medial septal-diagonal band area stands out as one of the major AChE cell collections in basal forebrain. In hypothalamus, neurons staining intensely for AChE occur particularly in supraoptic and paraventricular nuclei and in supramammillary nucleus. The neurons in lateral hypothalamic area stain only moderately for the enzyme. On the other hand, numerous large-sized AChE cells are scattered throughout the neostriatum. However, the AChE cells in putamen appear morphologically different, more numerous per mm2, and larger than those in caudate nucleus suggesting that the feline neostriatum is not a homogeneous structure. The globus pallidus contains both small and large cells that stain lightly and intensely for AChE, respectively. The small pallidal cells are similar to entopeduncular cells and it is proposed that they form the typical pallidal elements. In contrast, the large pallidal AChE cells appear similar to AChE neurons lying in adjacent substantia innominata, and are continuous with the AChE cells in medial septal-diagonal band area. It is suggested that these magnocellular AChE neurons form a population of "limbic" elements within the feline basal ganglia.
Seven episodes of rhabdomyolysis with acute renal failure (ARF) have been observed in 6 patients treated with various short-acting tranquilizers and antidepressants. Clinical features usually included severe hyperthermia, diffuse hypertonicity with or without coma, circulatory failure or unstable blood pressure, and often acute respiratory failure. Serum CPK were always elevated. The type of ARF was prerenal failure without oliguria in 5/7 episodes, and acute tubular necrosis in 2/7 episodes, requiring hemodialyses in one patient. Three patients died. In any case, the tranquilizers and antidepressants responsible for this syndrome were stopped, and electrolyte disorders and acidosis were corrected. Associated acute circulatory failure, septicemia and/or acute hepatic failure required prompt therapy, and artificial ventilation was required in 4 instances. The further use of phenothiazines, butyrophenones, sulpiride and their derivatives should be avoided in any patient having developed such an accident, whose pathophysiology is similar to that described in malignant hyperthermia of various origin.
The cat globus pallidus (GP) was found to contain both small and large cells that stain lightly and intensely for acetylcholinesterase (AChE), respectively. The small GP cells are similar to entopeduncular (EN) cells and it is proposed that both should be considered as 'typical' pallidal neurons. In contrast, large GP cells are similar to intensely stained AChE cells present in the substantia innominata (SI) and the putamen (PUT). Furthermore, HRP injection into the neocortex was found to label numerous large AChE cells in GP and a lesser number of similar neurons in PUT and SI. No HRP labeling was observed in the smaller cells of EN, GP and PUT. These findings suggest that the magnocellular AChE neurons in feline basal ganglia may be part of a single population of 'limbic' elements.
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The distribution of monoamine (MA)-containing nerve cell bodies in the brain stem of the chicken (Gallus domesticus) was studied by means of paraformaldehyde and glyoxylic acid fluorescent histochemical methods. The MA neurons were further characterized morphologically and histochemically in material prepared for the demonstration of acetylcholinesterase (AChE). In the rostral midbrain of the chicken, two large collections of catecholamine (CA)-containing cells are found: one located in the ventromedial and the other in the dorsolateral (pedunculopontine nucleus) portions of the tegmentum. On the basis of their topographic location, CA content, and fiber connections, these ventromedial and dorsolateral cell groups can be tentatively associated with the CA-containing neuronal populations of the mammalian ventral tegmental area and pars compacta of the substantia nigra, respectively. In the caudal midbrain of the chicken, numerous CA-containing cells are intermingled with serotonin (5HT)-containing perikarya beneath as well as within the decussation of the superior cerebellar peduncles. At isthmus levels, abundant, closely-packed CA-containing cells are encountered along the lateral border of the central gray. These neurons, which display a very high AChE activity, appear to be equivalent to those of the mammalian locus coeruleus. A multitude of medium-sized 5HT-containing neuronal somata occurs within the raphe region of the isthmus. Some of these somata closely surround the medial longitudinal fasciculus. This 5HT-containing cell group also massively invades the lateral tegmentum, where it becomes closely intermingled with the CA-containing neurons of the locus coeruleus and subcoeruleus. All of these 5 HT-containing neurons display a moderate to high AChE activity. In the medulla the number of MA-containing neurons is much smaller than in the upper brain stem. Nevertheless, 5HT-containing cells are present within the raphe region, particularly in the upper two-thirds of the medulla, and CA-containing perikarya can be found along the lateral border of the medulla and within the confines of the nucleus solitarius. The findings of the present study reveal that the MA-containing neuronal systems in the avian brain stem are organized according to a pattern that is much more complex than the one disclosed in reptiles or in other nonmammalian vertebrates. This complexity arises in large part from the fact that the 5HT-containing systems undergo a prominent lateralization in birds, which leads to a close intermingling of 5HT-containing and CA-containing neuronal elements at various levels of the neuraxis.
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Injections of horseradish peroxidase (HRP) involving the entire habenular complex in rat, cat and squirrel monkey (Saimiri sciureus) label (1) numerous cells in anterior lateral hypothalamic area, (2) a moderate number of cells in lateral preoptic area, substantia innominata, nucleus of diagonal band and postcommissural septum, and (3) a few cells in medial hypothalamus, ipsilaterally, in all three species. Some labeled cells also occur in corresponding regions contralaterally. The contribution of these limbic structures to the innervation of habenula is thus strikingly similar in the three groups. In contrast, significant species variations are found in respect to pallidal afferents. Whereas the entopeduncular nucleus in rat stands out as the main source of forebrain habenular afferents, the same structure in cat appears to contribute less substantially than adjoining lateral hypothalamus to the innervation of habenula. In monkey habenular afferents also arise principally from lateral hypothalamic neurons. At pallidal levels, labeled cells are nevertheless abundant in the rostral pole of primate internal pallidum. More caudally, they are found in significant number along internal and accessory medullary laminae where they intermingle with acetylcholinesterase-containing neurons which do not themselves project significantly upon habenula. This heterogeneous distribution of labeled pallidal cells indicates that the pallidohabenular projections in primate may arise, at least in part, from specific neuronal subpopulations within internal pallidum.