Dorsal mesencephalic projections to pons, medulla, and spinal cord in the cat: limbic and non-limbic components.

The vertebrate dorsal mesencephalon consists of the superior colliculus, the dorsal portion of the periaqueductal gray, and the mesencephalic trigeminal neurons in between. These structures, via their descending pathways, take part in various behavioral responses to environmental stimuli. This study was undertaken to compare the origins and trajectories of these pathways in the cat. Injections of horseradish peroxidase into the cervical spinal cord and upper medullary medial tegmentum retrogradely labeled cells mainly in the contralateral intermediate and deep superior colliculus, and in the ipsilateral dorsal and lateral periaqueductal gray and adjacent tegmentum. Only injections in the medullary lateral tegmental field labeled mesencephalic trigeminal neurons ipsilaterally. Autoradiographic tracing results, based on injections across the dorsal mesencephalon, revealed three efferent fiberstreams. A massive first fiberstream (limbic pathway), consisting of thin fibers, descended ipsilaterally from the dorsal and lateral periaqueductal gray and adjacent superior colliculus through the mesencephalic and pontine lateral tegmentum, terminating in these areas as well as in the ventral third of the caudal pontine and medullary medial tegmentum. A few fibers from the dorsal periaqueductal gray matter (PAG) were distributed bilaterally to the dorsal vagal, solitary, and retroambiguus nuclei. The second fiberstream (the predorsal bundle) descended contralaterally from the superior colliculus (SC) and consisted of both thick and thin labeled fibers. The thin fibers terminated bilaterally in the dorsomedial nucleus reticularis tegmenti pontis and the medial half of the caudal medial accessory inferior olive. The thick fibers targeted the contralateral dorsal two thirds of the caudal pontine and medullary medial tegmental fields, and the facial, abducens, lateral reticular, subtrigeminal, and prepositus hypoglossi nuclei. A few fibers recrossed the midline to terminate in the ipsilateral medial tegmentum. Caudal to the obex, fibers terminated laterally in the tegmentum and upper cervical intermediate zone. From the lateral SC, fibers terminated bilaterally in the lateral tegmental fields of the pons and medulla and lateral facial subnuclei. The third fiberstream (mesencephalic trigeminal or Probst tract) terminated in the supratrigeminal and motor trigeminal nuclei, and laterally in the tegmentum and upper cervical intermediate zone. In summary, neurons in the PAG and in the deep layers of the SC give rise to a massive ipsilateral descending pathway, in which a medial-to-lateral organization exists. A similar topographical pattern occurs in the crossed SC projections. The possibility that these completely different descending systems cooperate in producing specific defensive behaviors is discussed.     

Mesencephalic projections to the facial nucleus in the cat. An autoradiographical tracing study

In 33 cats the projections of different parts of the mesencephalon to the facial nucleus were studied with the aid of the autoradiographical tracing method. The results indicate the existence of many different mesencephalo-facial pathways. The dorsomedial facial subnucleus, containing motoneurons innervating ear muscles, receives afferents from 4 different mesencephalic areas: a, the most rostral mesencephalic reticular formation; b, the nucleus of Darkschewitsch and/or the ventral part of the rostral PAG; c, the interstitial nucleus of Cajal and/or the mesencephalic tegmentum dorsomedial to the red nucleus. These areas project bilaterally by way of an ipsilateral medial tegmental pathway. The medial part of the deep tectum. This area projects bilaterally by way of the tecto-spinal tract. The lateral mesencephalic tegmentum close to the parabigeminal nucleus. This area projects mainly contralaterally by way of a separate contralateral lateral tegmental fiber bundle. The mesencephalic tegmentum just dorsolateral to the red nucleus and perhaps from the dorsolateral red nucleus itself. This area projects contralaterally by way of the rubrospinal tract. The intermediate facial subnucleus containing motoneurons innervating the muscle around the eye, receives afferents from two different mesencephalic areas: The dorsal part of the rostral as well as caudal red nucleus (but not from its caudal pole) and from the dorsally adjoining mesencephalic tegmentum including the area of the nucleus of Darkschewitsch and the interstitial nucleus of Cajal. These areas project contralaterally by way of the contralateral rubrospinal tract. The nucleus of the optic tract and/or the olivary pretectal nucleus. This area projects contralaterally by way of a contralateral medial tegmental pathway. The lateral and ventrolateral facial subnuclei containing motoneurons innervating the muscles around the mouth receive afferents from two different mesencephalic areas: The lateral part of the deep tectal layers. This area projects contralaterally by way of the tecto-spinal tract. The nucleus raphe dorsalis and perhaps the nucleus centralis superior. This area projects by way of the lateral tegmentum of caudal pons and medulla.     

Termination patterns of serotoninergic medullary raphespinal fibers in the rat lumbar spinal cord: an anterograde immunohistochemical study

Electrical and chemical stimulation given in the ventral medullary raphe nuclei inhibits spinal nociceptive reflexes and spinal nociceptive transmission; serotoninergic receptors have been demonstrated to partially mediate that inhibition. In the present study, the termination patterns of raphespinal fibers in the rat lumbar spinal cord demonstrating serotonin-like immunoreactivity were examined by using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in combination with immunohistochemistry. Fibers and terminations from the ventral medullary raphe nuclei (raphe magnus and raphe pallidus) demonstrating both PHA-L- and serotonin-like immunoreactivity were identified in all laminae of the dorsal horn and the ventral horn. Networks of large fibers, characterized by large boutons, and which did not demonstrate serotonin-like immunoreactivity, were identified in deeper laminae of the dorsal horn. The heterogeneous morphology of raphespinal fibers identified in the dorsal horn suggests that these fibers also may be heterogeneous in neurochemistry and function. Medial medullary sites outside the raphe nuclei were found to innervate the ventral horn and all laminae of the dorsal horn, with the exception of lamina I. Descending fibers and terminations also demonstrating serotonin-like immunoreactivity were identified in deep laminae (III, IV, V, VI) of the dorsal horn and in the ventral horn. Similarly, large fiber networks were identified which did not demonstrate serotonin-like immunoreactivity.     

Demonstration of topographically organized projections from the hypothalamus to the pontine nuclei: an experimental anatomical study in the cat

In 22 cats implantations and injections of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) or Fluoro-Gold were placed in the pontine nuclei or the hypothalamus. The occurrence and distribution of labeled cells in the hypothalamus and of labeled terminal fibers in the pontine nuclei were mapped. Following implantations of HRP-WGA ventromedially in rostral parts of the pontine nuclei, 22-44% of all labeled cells in the brainstem and diencephalon are found in the medial mamillary nucleus ipsilateral to the implantation. Some labeled cells are also found in the supramamillary, premamillary, anterior mamillary, and tuberomamillary nuclei. Thus, labeled cells in the hypothalamus make up 33-54% of all labeled cells in the brainstem and diencephalon in such cases. In contrast, implantations and injections in mediocaudal parts of the pontine nuclei result in labeling of cells mainly in the posterior, dorsal, and lateral hypothalamic areas (terminology of Bleier: The Hypothalamus of the Cat. Baltimore: Johns Hopkins Press, '61). In these cases the labeled cells in the hypothalamus make up 16-25% of all labeled cells in the brainstem and diencephalon. Implantations in more lateral parts of the pontine nuclei label only a few cells in the hypothalamus. Following implantations of HRP-WGA in restricted parts of the hypothalamus, fibers from the medial mamillary nucleus were found to terminate ventromedially at all rostrocaudal levels of the pontine nuclei, ipsilateral to the implantation. In the rostralmost part of the pontine nuclei, the terminal labeling forms a dense, transversely oriented, c-shaped band. Fibers from the posterior and dorsal hypothalamic areas terminate medially and dorsomedially in the caudal third of the pontine nuclei. Sparse terminal labeling is also seen in lateral parts of the pontine nuclei and medially at more rostral levels. In two cases with small implantations of HRP-WGA ventromedially in rostral parts of the pontine nuclei, labeled cells are found both in the medial mamillary nucleus and the cingulate gyrus. Thus, it seems possible that fibers from the medial mamillary nucleus and the cingulate gyrus converge upon a restricted area ventromedially in rostral parts of the pontine nuclei.     

Hypothalamic projections to the ventral medulla oblongata in the rat, with special reference to the nucleus raphe pallidus: a study using autoradiographic and HRP techniques

Hypothalamic descending projections to the medullary ventral surface were studied autoradiographically in the rat. A small amount of [3H]leucine was injected unilaterally into various parts of the hypothalamus by air pressure. Abundant and characteristic terminal labelings were observed bilaterally in the nucleus raphe pallidus, the ventral surface of the pyramidal tract and the nucleus interfascicularis hypoglossi, after injections into the dorsal posterior hypothalamic area caudal to the paraventricular hypothalamic nucleus. Conspicuous, but less numerous labelings were observed in the nucleus raphe obscurus and the ipsilateral raphe magnus. After an injection of [3H]leucine into the hypothalamus and injections of horseradish peroxidase (HRP) into the spinal cord in the same animal, silver grains were densely distributed around HRP-labeled neurons in the nucleus raphe pallidus including the nucleus interfascicularis hypoglossi. The present results suggest that the dorsal posterior hypothalamic area projects directly to the spinal-projecting neurons of the nucleus raphe pallidus.     

Morphology of pontomedullary raphe and reticular formation neurons in the brainstem of the cat: an intracellular HRP study

In order to understand better the anatomical substrates underlying processing of sensory information, the cytoarchitecture of neurons in the pontomedullary raphe and reticular formation was investigated following intracellular injections of horseradish peroxidase in the cat. Raphe cells studied were located in the nucleus raphe magnus, nucleus raphe obscurus, and nucleus raphe pallidus. The most prominent type had a smooth, oval cell body and oval dendritic tree with dendrites extending laterally into the adjacent reticular formation. Two other raphe cell types, large cells with a dorsoventral orientation of both cell body and dendritic tree, and very small cells, were rarer. The primary dendritic orientation lay in the coronal plane for all three raphe cell types. Wispy, straight, or clublike spines were located on more distal regions of dendrites, although we also found spineless dendrites. Raphe cells lying near longitudinal fiber pathways exhibited bundling of dendrites around the passing axon fascicles. Reticular formation cells studied were located in the nucleus gigantocellularis, nucleus magnocellularis, nucleus paragigantocellularis dorsalis, and nucleus reticularis paramedianus. Two morphological types were found on the basis of dendritic branching patterns: sparsely branched and densely branched. Most reticular formation cells had round dendritic trees as viewed in the coronal plane and polygonal cell bodies that were medium to large in size. There was no correlation between reticular formation cell morphology and nuclear location. Spines were more common on the densely branched cells, but for both reticular cell types they were usually absent from cell bodies and proximal dendrites. Thus, by using the criteria of dendritic branching and arbor shape along with distance from the midline it was possible to identify raphe cells as distinct from reticular formation cells. In contrast, no morphological characteristics were found that would differentiate cells in the two major median reticular formation nuclei, gigantocellularis and magnocellularis.     

Serotonin- and substance P-containing projections to the nucleus tractus solitarii of the rat

The objective of the present study was to determine the location of the neurons that give rise to serotonin- and substance P-containing terminals in the nucleus tractus solitarii. This was done by injecting rhodamine-filled latex microspheres into the nucleus tractus solitarii of rats to retrogradely label neuronal cell bodies and by processing sections from the brains of these animals to determine whether the labelled neurons contained serotonin or substance P immunoreactivity. Serotonin-immunoreactive neurons that projected to the nucleus tractus solitarii were found in the nucleus raphe magnus, nucleus raphe obscurus, nucleus raphe pallidus, and in the ventral medulla, lateral to the pyramidal tract. Substance P-immunoreactive neurons that projected to the nucleus tractus solitarii were found in similar areas but were proportionately less numerous in the nucleus raphe magnus and proportionately more numerous in the nucleus raphe pallidus. It is concluded that neurons in the medullary raphe nuclei, some of which presumably utilize serotonin or substance P as a neurotransmitter, could regulate autonomic function via direct projections to the nucleus tractus solitarii.     

Projections between the hypothalamus and the dorsal vagal complex in the cat: An HRP and autoradiographic study

The hypothalamus is known to be intimately involved in the control of autonomic function. This study provides detailed information about pathways between the hypothalamus and the dorsal vagal complex in cat. Injection of horseradish peroxidase into the dorsomedial medulla produced retrograde neuronal labeling in the paraventricular nucleus of the hypothalamus. Injection of 3H-leucine into the paraventricular nucleus produced dense anterograde labeling in the dorsal motor nucleus of the vagus, and lighter labeling in the nucleus of the tractus solitarius, particularly in its medial subnucleus. The subnucleus gelatinous was virtually free of label, except in its medial and lateral portions. Anterograde labeling was distributed bilaterally, with an ipsilateral predominance. Injection of horseradish peroxidase into the area of the paraventricular nucleus produced retrograde neuronal labeling bilaterally in the nucleus of the tractus solitarius and the reticular formation ventrolateral to the dorsal vagal complex. anterograde terminal labeling overlapped the distribution of retrogradely labeled neurons. These findings are compared to those in rat, and discussed in relation to their functional implications.     

The organization of the gastric efferent projections in the brainstem of monkey: An HRP study

Topographic localization of neurons in the dorsal motor nucleus (DMN) of the vagus innervating the stomach and the extent of central decussation of its fibers were investigated in the monkeys after chronic unilateral cervical vagotomy. This study presents findings in regard to the non-topographic representation of the stomach in both DMN and lack of a well-defined decussation of its fibers in the brainstem of monkeys. Reported findings in the rat and cat vis-a-vis our own results in the monkey indicate species difference in the organization of efferent vagal gastric fibers. The evidence of a very small number of HRP-labeled cells in DMN on the vagotomized side after intervals of 2-36 weeks is being reported here, for what we believe to be the first time, and its significance has been discussed.     

Hypoalgesia induced by blockade of noradrenergic projections to the raphe magnus: reversal by blockade of noradrenergic projections to the spinal cord

Previous studies have demonstrated that microinjection of noradrenergic (NA) antagonists such as phentolamine in the nucleus raphe magnus (NRM) produces hypoalgesia. This hypoalgesia appears to result from disinhibition of raphe-spinal serotonergic neurons since it is blocked by intrathecally injected methysergide. The present studies demonstrate that the hypoalgesia produced by microinjection of phentolamine in the NRM is also abolished by intrathecal administration of phentolamine. The results suggest that the hypoalgesia produced by microinjection of NA antagonists in the NRM is also mediated, at least in part, by the activation of spinally projecting NA neurons. Such hypoalgesia does not appear to be mediated by activation of enkephalinergic neurons since intrathecal injection of the opiate antagonist naloxone did not attenuate the hypoalgesia.     

Electrophysiological studies of a rostral projection from the nucleus raphe magnus to the hypothalamus in the rat and cat

Neurones in nucleus raphe magnus (NRM) and the adjacent reticular formation with rostral projections were identified by their antidromic responses to stimulation at periventricular forebrain sites in rats and cats. In subsequent experiments, the effects of stimulation in the midline of the ventral medulla were tested on the activities of periventricular forebrain neurones. Taken together, the results of these experiments suggest that a direct inhibitory projection may exist from NRM to ventromedial forebrain structures including the anterior hypothalamus/preoptic region in rats in addition to polysynaptic pathways which mediate both excitations and inhibitions in rats and cats.     

Specificity of spinal projections from hypothalamic and brainstem areas which innervate sympathetic preganglionic neurons

The specificity and topographic organization of afferent projections to the intermediolateral column (IML) were examined using retrograde transport of fluorescent tracers injected into pairs of thoracic spinal segments. Neurons within the hypothalamus (parvocellular paraventricular nucleus, dorsomedial nucleus and lateral hypothalamus), pons (Kolliker-Fuse and A5 nuclei) and medulla (ventrolateral nucleus of the solitary tract and rostral ventrolateral medulla) each appeared to innervate only a single spinal segment. Neurons in each cell group projecting to different spinal segments were intermixed and showed no evidence of topographic organization. These results provide a potential anatomical substrate for organ-specific autonomic responses to physiological and psychological stimuli.     

Separate neurons in the paraventricular nucleus project to the median eminence and to the medulla or spinal cord

Double labeling experiments with the retrogradely transported fluorescent tracers bisbenzimide and True blue indicate that separate populations of cells in the paraventricular nucleus of the hypothalamus project to the median eminence and to the dorsomedial medulla or spinal cord in the rat. The cell populations giving rise to each projection are, however, at least partially intermixed in different parts of the nucleus.     

大鼠脑干SP能神经元向腰骶髓后连合核的投射

采用荧光金逆行标记和免疫荧光组织化学技术，观察了大鼠脑干ＳＰ能神经元向腰骶髓后连合核（ＤＣＮ）的投射状况。将ＦＧ压力注入ＤＣＮ后，脑干中缝苍白核、中缝隐核、中缝大核和巨细胞网状核α部腹外侧部的一些ＦＧ逆标神经元呈现ＳＰ样免疫反应阳性。结果表明，脑干的ＳＰ能下行纤维可终止于脊髓ＤＣＮ区。     

Localization of met-enkephalin-like immunoreactivity within pain-related nuclei of cervical spinal cord, brainstem and midbrain in the cat

Met-enkephalin immunoreactivity was investigated with an indirect immunoperoxidase technique in the cervical spinal cord, brainstem and midbrain of the cat, paying special attention to pain-related nuclei. Different technical conditions were used to reveal preferentially met-enkephalin-containing fibres and terminals or perikarya. Immunoreactive fibres and terminals were revealed optimally in sections from control animals incubated with detergent (Triton X-100). Immunoreactive perikarya were revealed in colchicine treated animals. Comparison between different routes of administration showed that local injections of colchicine are needed to reveal optimally immunoreactive perikarya in nuclei located far from the ventricles. Met-enkephalin-containing fibres and terminals are widely distributed in the posterior brain and spinal cord. The densest network of immunoreactive fibres are observed in the superficial layers of the cervical spinal cord and the caudal trigeminal nucleus, in the nucleus of the solitary tract, the nucleus of the facial nerve, the nucleus of the prepositus hypoglossi, the nucleus raphe pallidus, the medial vestibular nucleus, the interpedoncular nucleus and the substantia nigra. A moderate staining of fibres is observed in various nuclei including the ventral horn of the spinal cord and caudal trigeminal nucleus, the brainstem and midbrain reticular formation, the inferior olivary complex, the nucleus of the descending trigeminal tract and the periaqueductal grey. Met-enkephalin-containing perikarya are present in all the nuclei cited before, except in the inferior olivary complex. The densest aggregation of enkephalin-like perikarya is observed in the nucleus raphe magnus, nucleus raphe obscurus, nucleus raphe pallidus, nucleus reticularis gigantocellularis pars α and nucleus reticularis lateralis. The general distribution of enkephalin-containing structures in the cervical spinal cord, brainstem and midbrain of the cat appears very similar to that of the rat except in the substantia nigra where met-enkephalin cell bodies are found in the cat but not in the rat. In particular the pain-related nuclei present a similar distribution of the peptide in the two species; however, met-enkephalin-containing cell bodies are much more numerous in the cat than in the rat (notably in the reticular formation). Similar types of metenkephalin innervation occur in the dorsal and intermediate grey of the spinal cord and of the caudal trigeminal nucleus supporting further that the functional organizations of these regions are closely related.     

Direct projections from the globus pallidus to the paraventricular nucleus of the thalamus in the rat

After injecting horseradish peroxidase into the thalamic regions around the paraventricular thalamic nucleus (Pv) in the rat, small neurons in the globus pallidus (GP) were labeled retrogradely with the ezyme. After injecting [³H]leucine into the GP, terminal labeling was autoradiographically observed in the Pv bilaterally with an ipsilateral dominance. These terminals in the Pv were shown by electron microscopic autoradiography to make asymmetrical synaptic contacts upon small dendrites of Pv neurons.     

Primary afferent projections from dorsal and ventral roots to autonomic preganglionic neurons in the cat sacral spinal cord: light and electron microscopic observations

HRP applied to cut dorsal and ventral roots of the cat sacral spinal cord labeled afferent axons with swellings in close apposition to labeled preganglionic neurons (PGNs) in the sacral parasympathetic nucleus. Electron microscopy allowed characterization of synaptic contacts between afferents and PGNs. The results suggest that both the dorsal and ventral root afferents can directly activate autonomic preganglionic neurons.