The brainstem projection to the lateral geniculate nucleus in the cat: identification of cholinergic and monoaminergic elements

The pontomesencephalic projection to the dorsal lateral geniculate nucleus (dLGN) of the cat was analyzed by combining retrograde transport of rhodamine-labeled latex spheres and immunohistochemistry. After injections of latex beads into the dLGN, sections of the brainstem were treated immunohistochemically for choline acetyltransferase (ChAT), serotonin (Ser), tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH). Essentially, six regions in the brainstem contained retrogradely labeled cells: the superior colliculus, the parabigeminal nucleus, the dorsal raphe nuclei, the parabrachial area of the central tegmental field, the marginal nucleus of the brachium conjunctivum, and the nucleus coeruleus. Furthermore, isolated retrogradely labeled cells were present in the central nucleus of the raphe, in the cuneiform nucleus, and in the periaqueductal gray. Most serotoninergic double-labeled cells were found in the medial and lateral divisions of the dorsal raphe nuclei, but a few were also present in the central nucleus of the raphe. In the sections immunostained for ChAT, double-labeled cells were located in the central tegmental field, in the marginal nucleus of the brachium conjunctivum, and in the nucleus coeruleus. In the sections treated for TH and DBH, double-labeled cells showed a similar distribution, and like the ChAT(+) cells, they were located mainly in the central tegmental field, in the marginal nucleus of the brachium conjunctivum, and in the nucleus coeruleus. In these regions the cholinergic and noradrenergic cells that projected to the lateral geniculate nucleus were intermingled, the former predominating rostrally and the latter caudally. The majority of retrogradely labeled cells were located in the region of the central tegmental field in the vicinity of the brachium conjunctivum, and most of these cells were also ChAT-immunoreactive. We, therefore, conclude that the cholinergic projection is the most important of the central core projections ascending to the dLGN.     

Amygdaloid and pontine projections to the ventromedial nucleus of the hypothalamus

Amygdaloid and pontine projections to the feline ventromedial nucleus of the hypothalamus (HVM) were studied with retrograde transport of horseradish peroxidase (HRP) and anterograde transport of tritiated amino acids. Following injections of HRP into HVM, amygdaloid neurons were labeled in the ipsilateral cortical and medial nuclei and the ventral portion of the parvocellular part of the basal nucleus. In experiments in which HRP was injected into the tuberal hypothalamus following stria terminalis lesions, it was determined that amygdaloid neurons projecting to HVM by way of the stria terminalis were located in the cortical and medial nuclei while those projecting through another route, presumably the ventral amygdalofugal pathway, were found in the rostral part of the medial nucleus and the parvocellular basal nucleus. Following HRP injection into lateral hypothalamus at the level of HVM, labeled neurons were seen in the magnocellular basal nucleus. After preoptic injections, neurons containing the HRP reaction product were in cortical and medial nuclei and magnocellular and parvocellular parts of the basal nucleus. In addition to cells in the amygdala, rostral pontine neurons were labeled after HRP injections into HVM. The cells were located ipsilateral to the injection, mostly in the dorsal nucleus of the lateral lemniscus, lateral and dorsolateral to the brachium conjunctivum. The pontine cells labeled following HVM injections of HRP were different from those labeled following lateral hypothalamic and preoptic region injections. The pontine projection to HVM was confirmed using axoplasmic transport autoradiography. A mixture of tritiated leucine and tritiated proline was injected into the lateral pontine region labeled after HRP injections into HVM. Labeled axons ascending in the medial forebrain bundle terminated throughout the rostro-caudal extent of HVM.     

Cerebellothalamic projections in the rat: An autoradiographic and degeneration study

The purpose of this study was to determine the topographical organization of cerebellothalamic projections in the rat. Following stereotaxic injections of ³H-leucine or electrolytic lesions in the cerebellar nuclei, efferent fibers were observed to emerge from the cerebellum through two discrete routes. Fibers from the fastigial nucleus decussated within the cerebellum, formed the crossed ascending limb of the uncinate fasciculus, ascended in the dorsal part of the midbrain tegmentum, and entered the thalamus. Cerebellothalamic fibers from the interpositus and dentate nuclei coursed in the ipsilateral brachium conjuctivum, decussated in the caudal midbrain, and ascended to the thalamus via the crossed ascending limb of the brachium conjunctivum. Cerebellar terminations were observed in the intralaminar, lateral, and ventral tier thalamic nuclei as well as in the medial dorsal nucleus. Projections to the intralaminar nuclei were more pronounced from the dentate and posterior interpositus than from the anterior interpositus and fastigial nuclei. The lateral thalamic nuclei received a projection from the dentate and posterior interpositus nuclei while the fastigial nucleus projected to the medial dorsal nucleus. Within the rostral ventral tier nuclei fastigiothalamic terminations were localized in the medial parts of the ventral medial and ventral lateral nuclei, whereas dentatothalamic projections were concentrated in the lateral parts of the ventral medial nucleus and the medial half of the ventral lateral nucleus. Terminations from the posterior interpositus nucleus were observed ventrally and laterally within the caudal two-thirds of the ventral medial nucleus and throughout the ventral lateral nucleus, where they were densest in the lateral part of its lateral wing and within the central part of its cap. The anterior interpositus nucleus also projected to the central and lateral parts of the ventral lateral nucleus, but these terminations were considerably less dense than those from the posterior interpositus. A few fibers from the interpositus nuclei terminated in the medial part of the rostral pole of the ventral posterior nucleus. A prominent recrossing of cerebellothalamic fibers from the fastigial, posterior interpositus, and dentate nuclei occurred through the central medial nucleus of the internal medullary lamina. These terminated within the ipsilateral ventral lateral and intralaminar nuclei. These results show that each of the cerebellar nuclei project to the thalamus and that their terminations are topographically organized in the rostral ventral tier nuclei. The clustering of autoradiographic silver grains or terminal degeneration observed in the thalamic nuclei suggests a medial-to-lateral organization of this cerebellothalamic system.     

Characteristics of the neuronal activation of the pontine nuclei proper in the cat in cortico- and cerebellofugal impulse flow

Antidromic activation of the pontine nuclei neurons evoked by stimulation of brachium pontis, brachium conjunctivum (in rare cases), cerebellar central nuclei, pyramidal tract and sensorimotor cerebral cortex was studied in narcotized cats using the intracellular recording technique. The projection to the cerebellar lateral nucleus was shown to be the most pronounced among pontine nuclear projections. Monosynaptic excitation of the pontine nuclei neurons during stimulation of the pyramidal tract, cerebellar central nuclei and brachium conjunctivum was revealed. Peculiarities and significance of the connections revealed for the functioning of cortico-ponto-cerebellar system are discussed.     

Connections of the tectum of the rattlesnake Crotalus viridis: an HRP study.

We have studied the connections of the tectum of the rattlesnake by tectal application of horseradish peroxidase. The tectum receives bilateral input from nucleus lentiformis mesencephali, posterolateral tegmental nuclei, anterior tegmental nuclei and periventricular nuclei; ipsilateral input from nucleus geniculatus pretectalis, and lateral geniculate nucleus pars dorsalis; and contralateral input from dorso-lateral posterior tegmental nucleus and the previously undescribed nucleus reticularis caloris (RC). RC is located on the ventro-lateral surface of the medulla and consists of large cells 25--45 micrometer in diameter. Efferent projections from the tectum can be traced to the ipsilateral nucleus lentiformis mesencephali, the ipsilateral lateral geniculate region, anterior tegmental region and a wide bilateral area of the neuropil of the ventral tegmentum and ventral medualla. We have not found any direct tectal projections from the sensory trigeminal nuclei including the nucleus of the lateral descending trigeminal tract (LTTD). We suggest that in the rattlesnake, RC is the intermediate link connecting LTTD to the tectum.     

Efferent fibers of the deep cerebellar nuclei in hedgehogs

Three main deep cerbellar nuclei are apparent in hedgehogs belonging to the genera Erinaceus and Hemiechinus; however, at various levels they exhibit a considerable continuity with one another. Electrolytic unilateral lesions were placed in the deep cerebellar nuclei of these hedgehogs, and additional animals were subjected to a midline incision of the cerebellum between the two fastigial nuclei. Degenerating axons were traced from the sites of lesions using the Nauta and Fink-Heimer techniques. The typical mammalian pattern is evident in the distribution of the cerebellifugal fibers of the hedgehog. Crossed and uncrossed fastigial efferent fibers are directed primarily toward vestibular nuclei and the bulbar reticular formation except for a relatively small ascending limb of the uncinate fasciculus. The brachium conjunctivum originates from the nucleus interpositus and nucleus lateralis. The efferents of these nuclei are directed rostrally to the contralateral red nucleus. Fibers passing beyond the level of the red nucleus terminate in the thalamic nuclei. Fibers from the brachium conjunctivun also supply the inferior and superior colliculi. Axons forming the descending limb of the brachium conjunctivum are divided into medial and lateral fascicles.     

Distribution of somatostatin-28 (1-12) in the cat brainstem: an immunocytochemical study.

We studied the distribution of somatostatin-28 (1-12)-immunoreactive fibers and cell bodies in the cat brainstem. A moderate density of cell bodies containing the peptide was observed in the ventral nucleus of the lateral lemniscus, accessory dorsal tegmental nucleus, retrofacial nucleus and in the lateral reticular nucleus, whereas a low density of such perikarya was found in the interpeduncular nucleus, nucleus incertus, nucleus sagulum, gigantocellular tegmental field, nucleus of the trapezoid body, nucleus praepositus hypoglosii, lateral and magnocellular tegmental fields, nucleus of the solitary tract, nucleus ambiguous and in the nucleus intercalatus. Moreover, a moderate density of somatostatin-28 (1-12)-immunoreactive processes was found in the dorsal nucleus of the raphe, dorsal tegmental nucleus, accessory dorsal tegmental nucleus, periaqueductal gray and in the marginal nucleus of the brachium conjunctivum. Finally, few immunoreactive fibers were visualized in the interpeduncular nucleus, cuneiform nucleus, locus coeruleus, nucleus incertus, superior and inferior central nuclei, nucleus sagulum, ventral nucleus of the lateral lemniscus, nucleus praepositus hypoglosii, medial vestibular nucleus, K?lliker-Fuse area, nucleus ambiguous, retrofacial nucleus, postpyramidal nucleus of the raphe, nucleus of the solitary tract, dorsal motor nucleus of the vagus, lateral reticular nucleus and laminar and alaminar spinal trigeminal nuclei.     

Cerebellopontine projections in the American opossum. A study of their origin, distribution and overlap with fibers from the cerebral cortex

The origin, course and distribution of cerebellopontine fibers was studied in the opossum by employing the Nauta-Gygax and Fink-Heimer techniques. Our results substantiate and extnd those of Brodal, Destombes, Lacerda and Angaut ('72) concerning the existence of cerebellopontine projections and provide evidence for a hitherto unreported fastigial projection to the basilar pons. Destruction of the caudal, medial division of the fastigial nucleus elicits bilateral degeneration in a restricted area of the medial pontine nucleus. This small terminal field is located in the angle between the medial lemniscus and the pyramidal tract and is found throughout the caudal three-fifths of the pons. The degenerating fibers do not course within the descending brachium conjunctivum, but reach the pons by filtering through the reticular formation from the uncinate fasciculus. Lesions that involve either the interpositus anterior or the dentate nucleus produce degeneration within the contralateral descending brachium conjunctivum and basilar pons. Terminal fields are located within the median, medial (paramedian nucleus of cat), peduncular, ventral and lateral nuclei. The heaviest degeneration is in the medial nucleus. Although cerebellar and cortical projections have different targets in the basilar pons, there is some overlap. Fastigial and preorbital fibers have partial overlap in the dorsal part of the medial nucleus, whereas the peduncular and lateral nuclei are the areas of overlap between the interpositus anterior and dentate projections with those from forelimb (and probably face) cortical areas. This overlap is particularly obvious in the caudal part of the lateral nucleus and occurs between fibers from limb motor-sensory cortex and those arising mainly within the anterior interpositus nucleus. There is no pontine overlap between cerebellar and visual or auditory cortical projections.     

The cerebellopontine system in the rat. I. Autoradiographic studies

This study utilized light microscopic autoradiographic procedures to describe the projections from the three major subdivisions of the deep cerebellar nuclei (DCN) to the basilar pontine nuclei (BPN). Although the vast majority of cerebellopontine axons reached the BPN via the descending limb of the brachium conjunctivum (BC) after crossing the midline within the midbrain, a relatively small number of ipsilaterally projecting fibers was also observed. Fascicles of cerebellopontine axons left the main bundle of descending limb fibers throughout much of the rostrocaudal length of the BPN and passed around and through the medial lemniscus and cerebral peduncle to enter the pontine gray. The lateral cerebellar nucleus gave rise to the largest number of cerebellopontine fibers, whose terminal fields exhibited both diffuse and patchlike labeling patterns within each of the major subdivisions of the BPN including medial, ventral, lateral, and dorsal areas. Projections from the interpositus complex exclusive of its posterior division were fewer and less widely distributed than those from the lateral nucleus. Interpositopontine fibers terminated primarily in the caudal one-half of the BPN in medial, ventral, and lateral regions and overlapped somewhat with projections from the lateral cerebellar nucleus. Pontine projections emanating from the medial cerebellar nucleus were the fewest and most restricted in distribution relative to the other two cerebellar efferent systems. Such fibers formed a patchlike network of terminal fields which extended throughout much of the rostrocaudal length of the BPN in medial and dorsomedial regions. A relatively small but considerable number of ipsilateral cerebellopontine fibers terminated in pontine regions, which often mirrored the typical contralateral projection fields. Although it proved difficult to determine the precise origin of the ipsilateral fiber systems, it appeared that each of the three major DCN subdivisions made some contribution. Also it was apparent that considerable overlap existed between cerebellopontine projection zones and those of other pontine afferents including sensorimotor, visual, and auditory cortices, the superior colliculus, and the mammillary nuclei of the hypothalamus. Moreover, cerebellopontine terminal fields were congruent in some instances with discrete clusters of BPN neurons which serve as the source of pontocerebellar fiber systems, reaching portions of the lateral cerebellar hemispheres, posterior vermis, and the paraflocculus.     

Brainstem afferents to the lateral mesencephalic tegmental region of the cat

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

The efferent connections of the cerebellar nuclei in the pangolin

The connections of the cerebellar nuclei were traced in a primitive and specialized eutherian mammal, the pangolin, by placing varied unilateral lesions in the basal cerebellar nuclei and staining the ensuing fiber degeneration with the selective staining techniques of Marchi and Nauta. The results showed a cerebellifugal system that is basically similar to the pattern described for other mammals. The brachium conjunctivum arises primarily from the interpositus and dentate nuclei and follows the typical mammalian course and termination in the red nucleus and thalamus. In addition, a rather extensive termination in the dorsal mesencephalic tegmentum is present. A variation was observed in the descending limb of the brachium conjunctivum which divides into two tracts, medial and lateral. The fastigial projections are directed mainly to caudal rather than rostral areas with extensive terminations in vestibular and reticular areas. The present study establishes further the constancy of the general organization of cerebellar efferents in mammals and the primitive position of the cerebellifugal system in phylogeny. An assumption is made that the efferent connections of the cerebellum are present in one form in all therian mammals.     

Projections of the parabrachial nucleus in the pigeon (Columba livia).

The ascending and descending projections of the parabrachial nuclear complex in the pigeon have been charted with autoradiographic and histochemical (WGA-HRP) techniques. The ascending projections originate from a group of subnuclei surrounding various components of the brachium conjunctivum, namely, the superficial lateral, dorsolateral, dorsomedial, and ventromedial subnuclei. The projections are predominantly ipsilateral and travel in the quintofrontal tract. They are primarily to the medial and lateral hypothalamus (including the periventricular nucleus and the strata cellulare internum and externum), certain dorsal thalamic nuclei, the nucleus of the pallial commissure, the bed nucleus of the stria terminalis, the ventral paleostriatum, the olfactory tubercle, the nucleus accumbens, and a dorsolateral nucleus of the posterior archistriatum. There are weaker or more diffuse projections to the rostral locus coeruleus (cell group A8), the compact portion of the pedunculopontine tegmental nucleus, the central grey and intercollicular region, the ventral area of Tsai, the medial spiriform nucleus, the nucleus subrotundus, the anterior preoptic area, and the diagonal band of Broca. The parabrachial subnuclei have partially differential projections to these targets, some of which also receive projections from the nucleus of the solitary tract (Arends, Wild, and Zeigler: J. Comp. Neurol. 278:405-429, '88). Most of the targets, particularly those in the basal forebrain (viz., the periventricular nucleus and the strata cellulare internum and externum of the hypothalamus, the bed nucleus of the stria terminalis, and its lateral extension into the ventral paleostriatum, which may be comparable with the substantia innominata), have reciprocal connections with the parabrachial and solitary tract subnuclei and therefore may be said to compose parts of a "visceral forebrain system" analogous to that described in the rat (Van der Kooy et al: J. Comp. Neurol. 224:1-24, '84). The descending projections to the lower brainstem arise in large part from a ventrolateral subnucleus that may be comparable with the K?lliker-Fuse nucleus of mammals. They are mainly to the ventrolateral medulla, nucleus ambiguus, and massively to the hypoglossal nucleus, particularly its tracheosyringeal portion. These projections are therefore likely to be importantly involved in the control of vocalization and respiration (Wild and Arends: Brain Res. 407:191-194, '87). Some of these results have been presented in abstract form (Wild, Arends, and Zeigler: Soc. Neurosci. Abst. 13:308, '87).     

Biochemical mapping of the noradrenergic ventral bundle projection sites: Evidence for a noradrenergic-dopaminergic interaction

Norepinephrine (NE) and dopamine (DA) concentration and dopamine turnover were measured 12 days after a unilateral or bilateral noradrenergic ventral bundle (VB) transection to determine the noradrenergic projection sites and possible interactions with dopaminergic systems.Both bilateral and unilateral VB transection resulted in a significant reduction of NE of the nucleus accumbens, lateral septal nucleus, medial forebrain bundle, ventromedial nucleus, dorsomedial nucleus and medial amygdaloid nucleus. Bilateral transection also decreased NE content of the median eminence and the periventricular and arcuate nuclei. In the medial preoptic nucleus, the nucleus interstitialis striae terminalis and the central gray catecholamine area, bilateral transection significantly decreased NE concentrations while unilateral lesions had no significant effect. The anterior hypothalamic, lateral preoptic, and paraventricular nuclei responded to bilateral VB transection with a decrease in NE concentration and to unilateral lesion with a bilateral increase in NE. In the dorsal hippocampus and the caudate nucleus, bilateral lesions had no effect on NE concentrations while unilateral transection significantly decreased NE concentrations. Regions in which neither bilateral nor unilateral VB transection produced a significant change in NE content are the olfactory tubercle, the nucleus tractus diagonalis, substantia nigra pars compacta and reticulata, ventral tegmental area, habenula, superior colliculus, and the cingulate and piriform cortices.Transection of the noradrenergic ventral bundle also produced changes in dopaminergic systems suggesting a noradrenergic-dopaminergic interaction. Bilateral VB transection decreased the dopamine concentration and turnover in the nucleus accumbens, increased steady-state levels and turnover in the nucleus tractus diagonalis and increased dopamine concentration in the lateral septum. Unilateral VB transection decreased DA concentration bilaterally in the caudate nucleus, olfactory tubercle, nucleus accumbens and the nucleus interstitialis striae terminalis but increased concentrations in the substantia nigra pars reticulata (ipsilateral) and in the ventral tegmental area (bilateral). These results indicate a broad projection field for the noradrenergic ventral bundle and suggest a noradrenergic-dopaminergic interaction.     

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

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

Afferent projections to the ventral tegmental area of Tsai and interfascicular nucleus: a horseradish peroxidase study in the rat.

Using the retrograde transport of horseradish peroxidase (HRP), a study has been made of projections to the ventral tegmental area of Tsai (VTA) and related dopaminergic cell groups (A 10). In order to minimise the possibility of damage to fibres of passage, a technique was evolved for the microiontophoresis of HRP such that minimal current strengths and durations were applied. In addition to a sham injection, control injections were also made to the medial lemnisuc, red nucleus, deep tegmental decussations, mesencephalic reticular formation and brachium conjunctivum. Following HRP injections confined to the areas of the VTA containing the dopamine cell groups, labelled neurons appeared in prefrontal cortex, dorsal bank of rhinal sulcus, nucleus accumbens, bed nucleus of stria terminalis, amygdala, diagonal band of Broca, substantis innominata, magnocellular preoptic area, medial and lateral preoptic areas, anterior, lateral and postero-dorsal hypothalamus, lateral habenular, nucleus parafascicular nucleus of thalamus, superior colliculus, nucleus raphe dorsalis, nucleus raphe nagnus and pontis, dorsal and ventral parabrachial nuclei, locus coeruleus and deep cerebellar nuclei. Regions containing catecholamine groups A 1, A 5, A 6, A 7, A 9, A 13 and the serotonin group B 7 corresponded to the topography of labeled cell groups. Injections of HRP to the interfascicular nucleus resulted in labeling predominantly confined to the medial habenular and median raphe nuclei. The results are discussed in relation to the known connections of these regions. Other regions of the brain labelled by VTA injections are assessed in relation to control injections and the limitations of the HRP technique. A review of the organisation of some of these afferents in relation to the known cortical-subcortical-mesencephalic projection systems, suggests that the VTA is in a position to recieve information from a massively convergent system derived ultimately from the entire archi-, paleo-, and neo-cerebral cortices. In addition A 10 dopaminergic neurons are known to project to restricted regions of both pre-frontal and entorhinal cortices, which themselves also recieve massively convergent association cortico-cortical connections. It would appear reasonable to propose that these neurons perform a correspondingly important integrative function.     

Postnatal development of preproenkephalin mRNA containing neurons in the rat lower brainstem

Postnatal developmental changes of preproenkephalin (PPE) gene expression in rat brainstem neurons were studied by in situ hybridization histochemistry. On the basis of PPE mRNA expression, brainstem neurons were categorized into three types: 1) type I neurons were characterized by constant or increasing expression of PPE mRNA during postnatal development; 2) type II neurons started to express PPE mRNA several days after birth and continued to do so thereafter; and 3) type III neurons showed transient expression of PPE mRNA or stopped expressing the mRNA during early postnatal development. Type I PPE neurons were observed in diverse brainstem structures including the mesencephalic and pontine central gray matter, various reticular and raphe nuclei, the ventral tegmental area of Tsai, the interpeduncular nucleus, the nucleus of the brachium of the inferior colliculus, the ventral and dorsal tegmental nuclei of Gudden, the sphenoid nucleus, the laterodorsal tegmental nucleus, Barrington's nucleus, the parabrachial region, the lateral lemniscus and its related nuclei, the trapezoid nucleus, the rostral and ventromedial periolivary nuclei, the mesencephalic trigeminal and principal sensory trigeminal nuclei, the locus coeruleus, the subcoeruleus nucleus, the medial and spinal vestibular nuclei, the dorsal and ventral cochlear nuclei, the medial and lateral cerebellar nuclei, the Roller nucleus, and the intermedius nucleus of the medulla. Type II PPE neurons were found in the superior colliculus, the inferior colliculus, the central part of the dorsal tegmental nucleus, and as Golgi neurons in the granular layer of the cerebellum. Type III PPE neurons were located in the substantia nigra, the red nucleus, the superior olive, the motor trigeminal nucleus, the facial nucleus, the inferior olive, the dorsal motor nucleus of the vagus, and the hypoglossal nucleus. Such region-specific expression of the PPE gene during postnatal ontogeny suggests that rat brainstem PPE neurons may be involved in a variety of developmental events, such as cell proliferation, differentiation, and migration.     

Differential projections to the intralaminar and gustatory thalamus from the parabrachial area: a PHA-L study in the rat

The organization of projections from the parabrachial (PB) area to the ventral posterior parvicellular (VPpc) "gustatory" and intralaminar nuclei of the thalamus was studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA-L), into subregions of the PB area. The present study is a follow-up of three former studies (Bernard et al. [1993] J. Comp. Neurol. 329:201-229; Aldén et al. [1994] J. Comp. Neurol. 341:289-314; Bester et al. [1997a] J. Comp. Neurol. 383:245-281) that examined PB projections onto the amygdala, the bed nucleus of the stria terminalis, and the hypothalamus. Our data showed that (1) the region centered in the internal lateral PB subnucleus projects densely with a bilateral and symmetric pattern to the caudal portion of the paracentral and, to a lesser extent, to the adjacent portion of the central and parafascicular medial thalamic nuclei; (2) the mesencephalic PB region centered in the ventral lateral subnucleus and scattered neurons in the subjacent brachium conjunctivum project primarily, although diffusely, to the central medial thalamic nucleus. The third region includes two subgroups: (3a) the medial subgroup, including the medial, the waist area, and the ventral lateral subnuclei of the pontine PB area, projects bilaterally but with a weak ipsilateral predominance to the VPpc, terminals bearing large varicosities. Additionally, a diffuse projection with small varicosities spreads in the area between the two VPpc nuclei and the central medial nucleus. (3b) The lateral subgroup, centered in the external medial subnucleus, projects with a contralateral predominance in the periphery of the VPpc nuclei, most terminals being located around the dorsomedial tip. It is suggested that the PB projections to the intralaminar nucleus could be involved in cortical limbic arousal processing in relation with nociceptive, (somatic, visceral, and intraoral) and gustatory aversive stimuli. The projection with large varicosities inside the VPpc could process gustatory discrimination.     

Afferents to oculomotor nuclei from area "Y" in Macaca mulatta: an anterograde degeneration study

Electrolytic lesions were placed in the dentate and interpositus nuclei of the monkey M. mulatta and the resulting anterograde degeneration was stained with the Wiitanen or Nauta-Laidlaw techniques. Two of 19 lesions produced preterminal degeneration in the oculomotor nuclei. In both cases the lesions also damaged vestibular area “y” subjacent to the rostral pole of the dentate nucleus. The course and terminal distribution of anterograde degeneration to the oculomotor nuclei was the same in both cases. Degenerating fibers were found in lateral parts of the ipsilateral MLF, and preterminal degeneration was found in the ipsilateral abducens and trochlear nuclei and the dorsal subdivision of the oculomotor nucleus. Degenerating fibers were also traced from the crossed brachium conjunctivum to the contralateral paramedian subdivision of the oculomotor nucleus. These fibers appeared to course in dorsomedial parts of the brachium. Lesions of the dentate and interpositus nuclei which did not damage area “y” produced no anterograde axonal degeneration in the MLF or the oculomotor nerve nuclei. The results are discussed with regard to previous reports of cerebello-oculomotor fibers originating in the dentate and interpositus nuclei. The results suggest that area “y”, rather than the cerebellar nuclei, projects principally to oculomotor neurons that control vertical eye movements.     

Dopamine and norepinephrine levels in the nucleus accumbens, olfactory tubercle and corpus striatum following lesions in the ventral tegmentalarea.

Dopamine and norepinephrine levels were examined in 3 forebrain regions following unilateral lesions either in the ventral medial tegmental area (VMT) or in the substantia nigra. The dopamine and norepinephrine content of the nucleus accumbens, olfactory tubercle and corpus striatum were assayed ipsilaterally and contralaterally in unilaterally lesioned rats sacrificed 2, 5, 10, and 20 days after the placement of the lesions. In the nucleus accumbens and olfactory tubercle ipsilateral dopamine levels were significantly reduced below the contralateral levels at 2 days, and were decreased by 56% and 65%, respectively, 10 days after the lesion. A 30% reduction of dopamine levels occurred in corpus striatum as well, following lesions in the VMT. Lesions in the substantia nigra decreased ipsilateral dopamine levels by 68% in the corpus striatum, without affecting dopamine levels in the olfactory tubercle or nucleus accumbens. Norepinephrine levels on the side ipsilateral to the lesion did not significantly differ from contralateral levels in any of the 3 regions following lesions either in the VMT or in the substantia nigra. These results demonstrate the specificity of projection in the mesolimbic dopamine system as suggested by the original histofluorescence studies.     

A catecholaminergic projection from the ventral tegmental area to the diagonal band of broca: Modulation by neurotensin

The ventral tegmental area contains a high density of dopaminergic perikarya having ascending projections to a number of limbic forebrain regions. In this study, we use combined retrograde labeling with horseradish peroxidase (HRP) and immunohistochemical staining for tyrosine hydroxylase to examine the catecholaminergic projection from the ventral tegmental area to the diagonal band of Broca. When injection of HRP was restricted to the diagonal band, only neurons in the nucleus linearis, nucleus interfascicularis and ventromedial portion of the nucleus paranigralis were labeled. In contrast, HRP injection into the adjacent nucleus accumbens labeled neurons throughout these nuclei, plus the nucleus parabrachialis pigmentosus, nucleus retroruber and substantia nigra, pars compacta. Approximately 60% of neurons in the ventral tegmental area labeled from the diagonal band contained tyrosine hydroxylase, compared with 79% of the neurons labeled from the nucleus accumbens. Neurotensin is a tridecapeptide found in the ventral tegmental area which has been shown to activate dopamine neurons projecting to the nucleus accumbens. In this study, microinjection of neurotensin into ventral tegmental nuclei which contained neurons retrogradely labeled from the diagonal band significantly elevated the levels of dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the diagonal band. The results of this study demonstrate that a catecholaminergic projection exists from the ventral tegmental area to the diagonal band of Broca, and that this pathway can be stimulated by intra-ventral tegmental injection with neurotensin.