Calretinin-immunoreactive local circuit neurons in area 17 of the cynomolgus monkey,Macaca fascicularis

The connections of local circuit neurons immunoreactive for calcium-binding protein calretinin (CR-ir) were studied in area 17 of the macaque monkey visual cortex. Most CR-ir neurons were located in layers 2 and 3A. They were polymorphic and included bitufted, multipolar, pyramid-shaped neurons with smooth dendrites and Cajal-Retzius cells. The majority of CR-ir neurons were γ-aminobutyric acid (GABA)-immunopositive (approximately 90%), and comprised about 14% of the total GABAergic neuron population. The axons of CR-ir cells had local arbors within layers 1–3, but the major trunks descended to deep layers 5 and 6 where they formed dense terminal fields within narrow columns (100–150 μm). This specific innervation of layers 5 and 6 appeared as a distinct feature of area 17 as it was not seen in the adjacent area 18. CR-ir boutons (n = 168) were GABA-ir (95%) and formed symmetric synapses. In layers 1–3, the majority of postsynaptic targets (n = 64) were GABAergic local circuit neurons [postsynaptic target distribution: GABA-positive dendrites (67%) and somata (14%), and GABA-negative dendrites (13%) and spines (6%)]. In deep layers, the most synapses (80%; n = 187) were formed with pyramidal cells where they provided a basket-type innervation [postsynaptic target distribution: GABA-positive dendrites (19%) and somata (1%), and GABA-negative dendrites (50%), spines (20%) and somata (10%)]. Unlike other GABAergic neurons, which innervate mainly pyramidal neurons, the CR-ir subpopulation only has pyramids as a preferred target in the deep layers (layers 5 and 6); however, in the superficial layers of the area 17, they selectively form synapses mainly with other GABAergic cells. Thus, the CR-ir neurons appear to have a dual function of disinhibiting superficial layer neurons and inhibiting pyramidal output neurons in the deep layers. J. Comp. Neurol. 379:113-132, 1997. © 1997 Wiley-Liss, Inc.     

X-ray localization of limbic structures in the cynomolgus monkey (Macaca fascicularis)

The anterior/posterior (AP) and dorsal/ventral positions of 3 subcortical structures, the amygdala, the mamillary bodies, and the anterior commissure, were estimated with respect to the skull in a series of cynomolgus monkeys (Macaca fascicularis). The distance from the external auditory meatus, from which stereotaxic coordinates are typically derived, to these structures was found to be highly variable. In contrast, radiography revealed that a skull landmark which forms part of the sphenoid bone lies at a remarkably constant distance from these 3 structures. The posterior clinoid process also proved to be a more accurate reference point than the auditory meatus, although it was less reliable than the sphenoid landmark. It is proposed that the position of the sphenoid bone could be used to localize a wide range of limbic and basal forebrain structures.     

A stereotaxic atlas of the brain of the cynomolgus monkey (Macaca fascicularis)

Outline drawings of representative frontal sections of the Macaca fascicularis brain are presented in stereotaxic coordinates. The levels extend from the rostral tip of the neostriatum to the posterior end of the deep cerebellar nuclei. The illustrations are based on photographs of unstained frozen sections of three formalin-fixed brains in which stainless steel needles were inserted to mark the horizontal zero and several anteroposterior positions. The sections were not stained in order to prevent shrinkage. Stereotaxic measurements were taken in situ of the highest points on the cortical surface, the position of the central and lunate sulcus, and of certain landmarks at the base of the cranium in a large number of monkeys. These data along with brain dimensions and the weight of animals are displayed in tables to indicate individual variations and to aid investigators in determining the best stereotaxic coordinates for a given structure. It is recommended that the cortical point of entry for an electrode or needle be routinely noted and be compared to the parameters in the atlas to compensate for deviations in the horizontal plane.     

Cortical projections of the non-entorhinal hippocampal formation in the cynomolgus monkey (Macaca fascicularis)

Episodic memory consolidation requires the integrity of the anatomical pathways between the cerebral cortex and the hippocampal formation. Whilst the largest cortical output of the hippocampal formation originates in the entorhinal cortex, direct projections from CA1, subiculum and presubiculum to the cortex have been reported. The aim of this study is the assessment of the extent, topography and relative strength of those projections, as a parallel/alternate route of memory processing. A total of 45 injections in 28 Macaca fascicularis monkeys were used. Cortical deposits of fluorescent tracers (20 cases, 3% Fast Blue, 2% Diamidino Yellow) or 1% WGA-HRP (eight cases) were made in different cortical areas of the frontal, temporal and parietal lobes, as well as cingulate cortex by direct exposure of the cortical surface. After appropriate survival, animals were perfused and the brains serially sectioned at 50 microm and the retrograde labelling charted with an X-Y digitizing system. Retrograde neuronal labelling was observed in CA1, subiculum, presubiculum and parasubiculum; it was absent in the dentate gyrus, CA3 and CA2. Compared to other portions of the hippocampal formation, the CA1-subiculum border had the highest number of labelled neurons (especially after deposits in the rostral perirhinal cortex), followed by medial frontal cortex, temporal pole, orbitofrontal, anterior and posterior cingulate cortices, parietal and inferotemporal cortices, and no labelling after posterior inferotemporal and lateral frontal cortices. Our results indicate that CA1, subiculum, presubiculum and parasubiculum send direct output to cortical areas. This nonentorhinal, hippocampal formation cortical output may be relevant in memory processing.     

Projections from Gudden's tegmental nuclei to the mammillary body region in the cynomolgus monkey (Macaca fascicularis)

Gudden's tegmental nuclei provide major inputs to the rodent mammillary bodies, where they are thought to be important for learning and navigation. Comparable projections have yet to be described in the primate brain, where part of the problem has been in effectively delineating these nuclei. Immunohistochemical staining of tissue from a series of macaque monkeys (Macaca mulatta) showed that cells in the region of both the ventral and dorsal tegmental nuclei selectively stain for parvalbumin, thus helping to reveal these nuclei. These same tegmental nuclei were not selectively revealed when tissue was stained for SMI32, acetylcholinesterase, calbindin, or calretinin. In a parallel study, horseradish peroxidase was injected into the mammillary bodies of five cynomolgus monkeys (Macaca fascicularis). Retrogradely labeled neurons were consistently found in the three subdivisions of the ventral tegmental nucleus of Gudden, which are located immediately below, within, and above the medial longitudinal fasciculus. Further projections to the mammillary body region arose from cells in the anterior tegmental nucleus, which appears to be a rostral continuation of the infrafascicular part of the ventral tegmental nucleus. In the dorsal tegmental nucleus of Gudden, labeled cells were most evident when the tracer injection was more laterally placed in the mammillary bodies, consistent with a projection to the lateral mammillary nucleus. The present study not only demonstrates that the primate mammillary bodies receive parallel inputs from the dorsal and ventral tegmental nuclei of Gudden, but also helps to confirm the extent of these poorly distinguished nuclei in the monkey brain.     

Musculotopic organization of the hypoglossal nucleus in the cynomolgus monkey, Macaca fascicularis.

The movements of the tongue in feeding and vocalization are enabled by a complex system of interdigitated muscle fibers in the tongue body. Because of this complexity, the detailed anatomical connections between individual intrinsic tongue muscles and corresponding motoneurons in the hypoglossal nucleus have not been described for any mammal. In this study we describe the distribution of retrogradely labeled neurons in the hypoglossal nucleus, following injections of wheat-germ agglutinin-horseradish peroxidase into different regions of the tongue of 21 cynomolgus monkeys. These experiments demonstrate a spatial organization of hypoglossal motoneurons that reflects the anatomical and functional organization of tongue body muscles: motoneurons innervating the transversus and verticalis muscles are located in medial hypoglossal nucleus regions, motoneurons innervating the genioglossus are located in intermediate hypoglossal nucleus regions, motoneurons innervating the hyoglossus and inferior longitudinalis are located in ventrolateral hypoglossal nucleus regions, and motoneurons innervating the styloglossus and superior longitudinalis are located in dorsolateral hypoglossal nucleus regions. Motoneurons innervating the suprahyoid muscle, the geniohyoid, are situated in a cell column separated ventrally from the main body of the hypoglossal nucleus. Motoneurons innervating the palatoglossus are located in the nucleus ambiguus and, possibly, in dorsolateral hypoglossal nucleus regions. Motoneurons of the medial divisions of the hypoglossal nucleus innervate tongue muscles that are oriented in planes transverse to the long axis of the tongue whereas motoneurons of the lateral divisions innervate tongue muscles that are oriented parallel to this axis. These results suggest that the segregation of motoneurons corresponds to the functional distinction between tongue protrusion and retrusion.     

Abnormal neuronal and glial argyrophilic fibrillary structures in the brain of an aged albino cynomolgus monkey (Macaca fascicularis)

An aged albino male cynomolgus monkey (Macaca fascicularis) more than 35 years old died after showing neurological signs including gait disturbance, trembling, drowsing tendency and a decrease in activity. Neuropathological examination revealed glial fibrillary tangles (GFTs) mainly distributed in the putamen, caudate nucleus, thalamic nuclei, substantia nigra, red nucleus, globus pallidus, trapezoid body, pyramid, pons and medulla oblongata of the brain, and neurofibrillary tangles (NFTs) in the thalamic nuclei. These structures were positively stained by the modified Gallyas-Braak (GB) method and immunostained for tau. The tau-positive argyrophilic GFTs were morphologically classified into four types, as in human cases, i.e., tufts of abnormal fibers (TAFs), thorn-shaped astrocytes (TSAs), glial coiled bodies (GCBs) and argyrophilic threads (ATs) depending on their GB profiles, and GCBs were the major structures in this case. Some of these structures were also immunoreactive for α-synuclein. The glial cells possessing the structures were negative for glial fibrillary acidic protein, a marker for astrocytes, indicating that the argyrophilic GFTs were present in oligodendroglia. In addition, marked neuronal loss and ubiquitin-positive spheroid bodies were observed in the substantia nigra and globus pallidus. According to the characteristic distribution of the argyrophilic structures in neurons and glial cells as well as clinical signs, the monkey might have suffered from a neurodegenerative disease such as progressive supranuclear palsy (PSP). This is the first report of the occurrence of a neurodegenerative disease in a nonhuman animal. Received: 16 November 1999 / Revised, accepted: 31 January 2000     

Laminar distribution of receptors in monkey (Macaca fascicularis) geniculostriate system

We have examined the laminar distributions of eight types of receptor in the primary visual cortex (area 17) and the lateral geniculate nucleus (LGN) of the macaque monkey. The receptor populations and subpopulations examined included those selective for gamma-aminobutyric acid (GABA) (using [3H]-muscimol as ligand), L-glutamate-related receptors (using [3H]-L-glutamate and [3H]-AMPA), muscarinic acetylcholine (using [3H]-quinuclidinyl benzilate--QNB and [3H]-N-methyl scopolamine--NMS), cholecystokinin (CCK) (using [3H] pentagastrin), benzodiazepine (using [3H]-flunitrazepam), and adenosine (using [3H]-cyclohexyladenosine--CHA). Each of the receptors examined exhibited characteristic and differing laminar patterns of binding in the striate cortex. Perhaps reflecting the high density of cell bodies and synapses in layer 4C, most receptors, except those labelled by [3H]-L-glutamate or [3H]-AMPA, showed dense concentrations in this layer. Layers 4B and 5, which contain relatively few cell bodies and heavy myelin concentrations, were in general lightly labelled. Layer 6 showed relatively heavy labelling when [3H]-AMPA (quisqualate) or [3H]-pentagastrin (CCK) were used as ligands. The superficial layers of the cortex were zones of relative concentration of GABA, benzodiazepine, acetylcholine, glutamate-related, and adenosine receptors. In general, the binding patterns resembled those previously described for cat visual cortex, but there were also some clear differences. The distributions of all of these receptors likely reflect the differential input substances to different laminae of the visual cortex. Of the receptors examined, only those for GABA, benzodiazepine, and acetylcholine were found in substantial concentration in the LGN. Of these, GABA and benzodiazepine receptors showed especially dense binding in the magnocellular layers of the LGN compared to the parvicellular layers.     

Induction of acquired factor IX inhibitors in cynomolgus monkey (Macaca fascicularis): a new primate model of hemophilia B

Inherited hemophilia dog and other transient hemophilic animal models have been used for evaluation of hemostatic agents for use in treatment of hemophilia. We established the first nonhuman primate hemophilic model by immunizing cynomolgus monkeys with human FIX (hFIX) in adjuvants. FIX activities of all three hFIX-immunized monkeys decreased transiently to less than 10% in accordance with prolongation of activated partial thromboplastin time (APTT). Forty micrograms of human factor VIIa (hFVIIa) per kilogram body weight (that was reported to be clinically effective) was administered to the monkey with the highest inhibitor titer to evaluate its usefulness as a hemophilia inhibitor model. Results of thromboelastography (TEG) after the injection demonstrated that the hemostatic effect of FVIIa in this model would be similar to that in hemophiliacs with inhibitors. The antibodies purified from the monkey's plasma by hFIX-immobilized gel were composed of two types: Ca(2+)-dependent and -independent antibodies, with features of IgG(1) and IgG(4). Both types of antibodies reacted to cynomolgus FIX, and only Ca(2+)-dependent antibodies also expressed inhibitory activity against cynomolgus FIX. Immunoblotting analyses of Ca(2+)-dependent antibodies using hFIX and its derivatives suggested that they recognized the Ca(2+)-dependent conformation related to the gamma-carboxyglutamic acid (Gla) domain. Comparison of FIX cDNA from human, cynomolgus monkey, and other species, and the results of immunization of various animals (goats, beagle dogs, rabbits, and rats) with hFIX in adjuvants strongly suggested that the development of acquired FIX inhibitors in the monkeys might be due to high cross-reactivity of the antibodies to molecular mimic antigens, hFIX, and cynomolgus FIX.     

Central projections and trigeminal ganglion location of corneal afferent neurons in the monkey, Macaca fascicularis

The method of transganglionic transport of horseradish peroxidase-wheat germ agglutinin conjugate (HRP-WGA) was used to determine the location within the monkey trigeminal ganglion of the primary afferent neurons that innervate the cornea, and the brainstem and spinal cord termination sites of these cells. In each of four animals. Gelfoam pledgets were saturated with 2% HRP-WGA in saline and applied to the scratched surface of the central cornea for 30 minutes. Postmortem examination of the corneal whole mounts revealed that the tracer solution remained confined to approximately the central one-fourth of the cornea with no spread into the peripheral cornea or limbus. Seventy-two to 96 hours after tracer application, 126-242 labeled cell bodies were observed in the medial region of the ipsilateral trigeminal ganglion. The majority of neurons were concentrated in an area of the ganglion that lay directly caudal to the entering fibers of the ophthalmic nerve, but smaller numbers of cells lay somewhat more laterally, near the region where the ophthalmic and maxillary nerves come together. A very small number of neurons in one animal innervated the cornea by sending their fibers into the maxillary nerve. HRP-WGA-labeled terminal fields were present to some extent in all four major rostrocaudal subdivisions of the ipsilateral trigeminal brainstem nuclear complex (TBNC), but the size of the terminal fields and the intensity of labeling differed markedly from one level of the TBNC to the next. Labeled fibers projected heavily to the transitional zone between caudal pars interpolaris and rostral pars caudalis (i.e., the "periobex" region of the TBNC) and moderately to the trigeminal main sensory nucleus, pars oralis, and caudal pars caudalis at the level of the pyramidal decussation. Remaining areas of the TBNC, including rostral pars interpolaris and the midlevel of pars caudalis, received few, if any, corneal afferent projections. Occasional labeled fibers were observed in the dorsal horn of C1 and in the rostral half of C2. It is hoped that data generated in the current investigation of nonhuman primates will contribute to a better understanding of the neural substrates that subserve corneal sensation and the blink reflex in humans.     

Vasoactive intestinal polypeptide nerve fibers in human and monkey (Macaca fascicularis and Macaca mulatta) kidneys

Nerve fibers immunoreactive for vasoactive intestinal polypeptide (VIP) were demonstrated for the first time by the indirect immunofluorescence technique in human and monkey kidneys. VIP-immunoreactive nerve fibers showing varicosities were observed in the adventitia of arcuate arteries and their branches. The density of VIP-immunoreactive nerve fibers decreased from the juxtamedullary region to the cortex. Occasionally a VIP-immunoreactive varicose nerve fiber was observed near the vascular pole of a glomerulus, but no direct innervation of afferent or efferent arterioles in either monkey or human kidney was found. The distribution of VIP-immunoreactive nerve fibers in the monkey and human kidneys was similar to that reported in other species, with less density. The functional role of VIP in the innervation of the kidney is not known, but various suggestions have been made regarding the possible involvement of VIP on vasodilation of selective intrarenal blood vessels, renin secretion, and/or effects on tubules. While none of these questions were established at this time they would appear to be logical areas for further study.     

Symptoms and behavioral features induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in an old Java monkey [Macaca cynomolgus fascicularis (Raffles)]

The study concerns symptoms and behavioral characteristics induced by MPTP in a 20-year-old Macaca cynomolgus fascicularis, their evolution over 7 months, and the animal's response to 1-dopa treatment. The symptoms which the animal developed include those that have been described earlier in Macaca mulatta and Saimiri sciureus, i.e., rigidity, action tremor, postural tremor, postural flexion, hypokinesia, and bradykinesia. In addition, however, the animal developed a 3.8 Hz resting tremor which in humans is pathognomonic of Parkinson's disease, as well as cogwheeling, the glabellar tap sign, drooling, impaired ability to relax, and many other symptoms. Also unlike previously described MPTP monkeys, the animal's symptoms neither improved spontaneously, nor did they remain stable shortly after MPTP injection. Instead, symptoms steadily progressed to reach a severe status 2 months after MPTP, and further progression was apparent after another 5 months. Therapeutic responses to 1-dopa required accumulation of or kindling by the 100 mg unit doses that were spaced 4 hr apart, were often organized in time as ON episodes that alternated with OFF episodes, and were associated with dyskinesias and bizarre behavior. Of particular interest is that the animal showed kinesia paradoxa which, in humans, constitutes a feature that is unique to Parkinson's disease among the extrapyramidal disorders. In addition to available evidence, the present findings validate the syndrome induced by MPTP in monkey as an animal analogue of Parkinson's disease. Taxonomic category, age, and the occurrence of shock in response to MPTP are discussed as variables that may possibly co-determine the pathology which MPTP may induce in monkey.     

Differential development and electrophysiological activity in cultured cortical neurons from the mouse and cynomolgus monkey

In vitro cultures of primary cortical neurons are widely used to investigate neuronal function. However, it has yet to be fully investigated whether there are significant differences in development and function between cultured rodent and primate cortical neurons, and whether these differences influence the utilization of cultured cortical neurons to model pathological conditions. Using in vitro culture techniques combined with immunofluorescence and electrophysiological methods, our study found that the development and maturation of primary cerebral cortical neurons from cynomolgus monkeys were slower than those from mice. We used a microelectrode array technique to compare the electrophysiological differences in cortical neurons, and found that primary cortical neurons from the mouse brain began to show electrical activity earlier than those from the cynomolgus monkey. Although cultured monkey cortical neurons developed slowly in vitro, they exhibited typical pathological features-revealed by immunofluorescent staining-when infected with adeno-associated viral vectors expressing mutant huntingtin(HTT), the Huntington's disease protein. A quantitative analysis of the cultured monkey cortical neurons also confirmed that mutant HTT significantly reduced the length of neurites. Therefore, compared with the primary cortical neurons of mice, cultured monkey cortical neurons have longer developmental and survival times and greater sustained physiological activity, such as electrophysiological activity. Our findings also suggest that primary cynomolgus monkey neurons cultured in vitro can simulate a cell model of human neurodegenerative disease, and may be useful for investigating time-dependent neuronal death as well as treatment via neuronal regeneration. All mouse experiments and protocols were approved by the Animal Care and Use Committee of Jinan University of China(IACUC Approval No. 20200512-04) on May 12, 2020. All monkey experiments were approved by the IACUC protocol(IACUC Approval No. LDACU 20190820-01) on August 23, 2019 for animal management and use.     

The morphology and connections of the posterior hypothalamus in the cynomolgus monkey (Macaca fascicularis). II. Efferent connections

The efferent connections of the posterior hypothalamus have been analyzed autoradiographically in a series of eight cynomolgus monkey (Macaca fascicularis) brains with injections of ³H-amino acids in different regions of the mamillary complex and the surrounding areas. The medial mamillary nucleus was found to project through the mamillothalamic tract to the ipsilateral anteroventral, anteromedial, and interanteromedial nuclei, and by way of the mamillotegmental tract principally to the deep tegmental nucleus (of Gudden). It also appears to contribute fibers to the medial forebrain bundle, some of which reach as far rostrally as the medial septal nucleus. The lateral mamillary nucleus projects through the mamillothalamic tract bilaterally upon the anterodorsal nuclei of the thalamus, and through the mamillotegmental system to the dorsal tegmental nucleus; it also appears to contribute fibers to the medial forebrain bundle. The supramamillary area has extensive ascending and descending connections that are distributed with the medial forebrain bundle to the hypothalamus and rostral midbrain; in addition, it gives rise to an unusually well-defined projection to field CA2 of the hippocampus and to a narrow zone overlying the outer part of the granule cell layer and the adjoining part of the molecular layer of the dentate gyrus. We have not been able to distinguish the connections of the posterior hypothalamic nucleus from those of the caudal part of the lateral hypothalamic area: they both appear to contribute substantially to the ascending components of the medial forebrain bundle, and through its descending projection to the tegmental fields of the midbrain, the nucleus centralis superior of the raphe complex, the locus coeruleus, and the central gray as far caudally as the facial nerve. Their further projections to the spinal cord were not examined. Viewed broadly, and in the light of previous work, our observations confirm, once again, the constancy of the connections of the hypothalamus in the mammalian brain, and the pivotal position that the posterior hypothalamus occupies in the elaborate system of connections that links the limbic areas of the forebrain with the complex of structures that Nauta has aptly designated the “midbrain limbic region”.     

The morphology and connections of the posterior hypothalamus in the cynomolgus monkey (Macaca fascicularis). I. Cytoarchitectonic organization

The cytoarchitectonic organization of the posterior hypothalamus of the cynomolgus monkey (Macaca fascicularis) was analyzed in Nissl, Golgi, acetylcholinesterase, and reduced silver preparations. The region consists of a number of cell masses that differ considerably in their discreteness and in the homogeneity of their neuronal populations. The nuclei identified include: the medial mamillary nucleus (in which at least three distinct subdivisions can be recognized—a pars medialis, a pars lateralis, and a pars basalis); the small-celled nucleus intercalatus; the large-celled lateral mamillary nucleus; a single premamillary nucleus; the tuberomamillary nucleus; the posterior hypothalamic nucleus; the caudal extension of the lateral hypothalamic area; the supramamillary area; and the paramamillary nucleus (which appears to correspond to the nucleus of the nucleus of the ansa lenticularis of other workers). As a basis for the subsequent experimental study of the efferent connections of the posterior hypothalamus, the location of each of these cell masses is described and illustrated in a series of low-power photomicrographs, as are the form and distribution of the resident neuronal populations of the various components of themamillary complex as seen in Golgi preparations.     

Transplantation of embryonic serotonin immunoreactive neurons into the transected spinal cord of adult monkey (Macaca fascicularis).

Five adult monkeys (Macaca fascicularis) underwent a total section of the spinal cord at the thoracic level (T6). Four of them received a daily treatment with cyclosporin (10 mg/kg). Ten days later, two animals treated with cyclosporin and one without cyclosporin received at T8 and T10 levels an injection of a cell suspension prepared from the rhombencephalon of a 40-day-old macaque embryo. Two control animals received one injection of Hank's balanced salt solution. The animals were sacrificed after 2 months (one grafted and one control) and 3 months (two grafted and one control), and their spinal cord was processed for the immunocytochemical detection of serotonin using light and electron microscopy. After 2 months of survival, serotonergic neurons had survived and developed within the transplant. Three months after transplantation, in the animal treated with cyclosporin, serotonergic neurons were found to survive with their axons growing into the host grey matter and establishing axosomatic and axodendritic synapses in the ventral horn. If the graft was isolated in the white matter no fibers were seen invading the grey matter.     

Projections of thalamic gustatory and lingual areas in the monkey, Macaca fascicularis

The efferent projections of the parvicellular division of the ventroposteromedial nucleus of the thalamus (VMPpc; thalamic taste area) were traced to cortex in Macaca fascicularis by using tritiated amino acid autoradiography. Labeled fascicles could be traced from VPMpc to two discrete regions of cortex. The primary efferent projection was located on ipsilateral insular-opercular cortex adjacent to the superior limiting sulcus and extended as far rostrally as the posterior lateral orbitofrontal cortex. An additional projection was located within primary somatosensory (SI) cortex subjacent to the anterior subcentral sulcus. Following autoradiographic injections in VPM, the trigeminal somatosensory relay, a dense terminal plexus was labeled on SI cortex of both pre- and postcentral gyri, but not within insular-opercular cortex. The autoradiographic data were verified by injecting each cortical projection area with horseradish peroxidase (HRP) and observing the pattern of retrogradely labeled somata within the thalamus. Injections in the precentral gyrus near the anterior subcentral sulcus retrogradely labeled neurons within VPMpc, whereas injections further caudally near the floor of the central sulcus labeled neurons within VPM. Injections of HRP within opercular, insular, or posterior lateral orbitofrontal cortex retrogradely labeled neurons within VPMpc.     

Funicular trajectories of brainstem neurons projecting to the lumbar spinal cord in the monkey (Macaca fascicularis): a retrograde labeling study

Brainstem nuclei projecting to the lumbar spinal cord in the monkey were identified by using horseradish peroxidase and the fluorescent dye granular blue. These retrogradely transported tracers were used in fluid and/or gel forms to determine the funicular trajectories of the brainstem-spinal projections. The major descending components of the dorsal funiculus arose from the n. gracilis, n. cuneatus, and the n. of the solitary tract. Major components of the dorsolateral funiculus (DLF) came from the raphe complex, medullary and pontine reticular formation, locus coeruleus, Edinger-Westphal n., and red n. Other nuclei giving rise to minor contributions to the DLF included n. gracilis, n. cuneatus, n. of the solitary tract, medial and spinal vestibular n., subcoeruleus, periaqueductal gray, interstitial n. of Cajal, n. of Darkschewitsch, and the anteromedian n. The major components of ventral cord paths (ventrolateral and ventral funiculi) arose from the raphe complex, the medullary and pontine reticular formation, lateral and spinal vestibular n., and the coerulean complex. Minor contributions to the ventral paths descended from the dorsal motor n. of X, n. of the solitary tract, medial vestibular n., paralemniscal reticular formation, dorsal parabrachial n., n. cuneiformis, periaqueductal gray, K?lliker-Fuse n., and red n. The possible functional implications of the funicular distribution of these descending pathways are discussed from the perspective of descending inhibition and pain modulation.