Organization of the ascending striatal afferents in monkeys

Horseradish peroxidase was injected in various parts of the caudate nucleus and the putamen of monkeys to ascertain the relative locations of striatal projecting cells in the mesencephalon. The nigrostriatal component, as expected, is the greatest but numerous cells of the mesencephalic raphe system also project to the striatum. The projections from the pars compacta are organized in a topographical manner in all principal planes. The rostral two thirds of the substantia nigra are related to the head of the caudate nucleus. Nigral neurons projecting to the putamen are more posteriorly located and display an anteroposterior topography. The medial two thirds of the pars compacta send efferents to the head of the caudate nucleus from ventromedial to laterodorsal regions, reflecting a mediolateral topographical relationship. An inverse relationship exists dorsoventrally between nigra and caudate so that ventral compacta cells project to dorsal caudate and the dorsally situated neurons project to ventral-ventro-medial caudate regions. The dorsal and lateral parts of the putamen are more intimately related to the lateral and posterior nigra; by contrast, the ventral and ventromedial putamen receives more afferents from medial and central regions of the substantia nigra. A large group of cells in the tegmentum dorsal and medial to the medial lemniscus shows continuity with the pars compacta, and has similar connections with the striatum. This cell group should be included with the pars compacta. Significant overlap exists between the projection fields in all planes, making the nigrostriatal topographical organization seem less than precise. This apparent lack of point-to-point reciprocity may be due to the considerable size difference between the striatum and the substantia nigra. The raphe nuclei project to the greater part of the striatum but more significantly to its ventral and medial regions. The paranigral cell group sends its efferents mainly to the ventral striatum.     

The sites of origin of dopaminergic afferent fibers to the lateral habenular nucleus in the rat

The lateral habenular nucleus of the rat contains a dense plexus of dopaminergic fibers, which are more marked in the medial part of the lateral habenular nucleus than in its lateral counterpart. Employing a combination of fluorescent retrograde axonal tracing with fluorogold and tyrosine hydroxylase immunofluorescence histochemistry, we investigated the distribution of cells of origin of the dopaminergic afferent fibers to the lateral habenular nucleus in the rat. The cells double-labeled with both fluorogold injected into the lateral habenular nucleus and tyrosine hydroxylase antisera were seen in a variety of fore- and midbrain regions, including the bed nucleus of the stria terminalis, medial preoptic area, periventricular, ventromedial, and dorsomedial hypothalamic nuclei, ventral tegmental area, interfascicular nucleus, substantia nigra pars compacta, ventrolateral division of the midbrain periaqueductal gray, and dorsal raphe nucleus. The double-labeled cells were located bilaterally with an ipsilateral predominance, and constituted approximately 10% of the total fluorogold-positive cell population. We have further observed by anterograde axonal tracing with Phaseolus vulgaris–leucoagglutinin that projection fibers arising from the sites of origin of the dopaminergic afferent fibers to the lateral habenular nucleus terminate mainly in the medial part of the lateral habenular nucleus, and to a lesser extent in its lateral conterpart. Thus, we have found in the present study that the dopaminergic neurons sending their axons to the lateral habenular nucleus are widely distributed in the A9, A10, A14, and A15 dopaminergic cell groups. Such dopaminergic neurons may exert regulatory influences upon many limbic-associated brain regions via the lateral habenular nucleus. © 1993 Wiley-Liss, Inc.     

Topographic organization of the brainstem afferents to the mediodorsal thalamic nucleus

The afferent projections from the brainstem to the mediodorsal thalamic nucleus (MD) were studied in the cat, by means of retrograde transport of horseradish peroxidase. A topographical arrangement of these projections is described. The medial part of MD is the area of the nucleus which receives fewer afferents from the brainstem. After injections in this part, labeled neurons were observed mainly in the interpeduncular nucleus, the ventral tegmental area and the substantia nigra. After injections of HRP in the intermediate part of the MD, labeled cells were seen mainly in the interpeduncular nucleus, substantia nigra, dorsal and centralis superior raphe nuclei, dorsal tegmental nucleus, and coeruleus complex. Less conspicuous was the number of labeled cells in the central gray and the dorsolateral portion of the tegmentum of the mesencephalon and pons. After injections in the lateral part of MD, labeled neurons were observed mainly in the deep layers of the superior colliculus, central gray, the oral paramedian pontine reticular tegmentum, and the interpeduncular nucleus. Labeled cells were also observed in the substantia nigra, locus coeruleus, dorsal tegmental nucleus, cuneiform area, and the mesencephalic reticular formation. These findings show the MD as a thalamic link of three different groups of brainstem structures projecting to different cortical areas with different functional significance.     

Monoamine distribution in primate brain V. Monoaminergic nuclei: Anatomy,pathways and local organization

The noradrenergic, dopaminergic, and serotonergic cell groups of the brain stem and caudal diencephalon, and their projections, were examined in neonatal and adult squirrel monkeys, rhesus monkeys, and stump-tail monkeys utilizing the Falck-Hillarp formaldehyde condensation reaction. The axonal pathways fluoresced in neonatal monkeys and permitted direct visualization of the major bundles. Cell groups in the ventral and dorsal tegmentum of the medulla and pons (A1, A2, A3, A7) gave rise to a ventral ascending catecholamine pathway which coursed through the ventral tegmentum of the brain stem. The locus coeruleus (A4, A6) gave rise to a dorsal ascending catecholamine pathway which coursed through the medial region of the tegmentum above the ventral pathway. Prominent catecholamine cell bodies (Acg) in the central gray of the midbrain, rostral to the locus coeruleus, gave rise to an ascending dorsal periventricular pathway which ran dorsally in the tegmentum; some fibers then rapidly coursed ventrally to join a confluence with other ascending brain stem catecholamine axonal projections. The catecholamine axons ran through the medial forebrain bundle in the lateral hypothalamus, and sent further projections into limbic forebrain and cortical structures. Dopaminergic cells of the ventral tegmental area gave rise to an ascending ventral periventricular system which coursed through the most ventromedial region of the tegmentum, entered the medial forebrain bundle, and further coursed into regions of frontal and cingulate cortex, and limbic forebrain regions. The substantia nigra and some lateral cells of the lateral ventral tegmental area sent axons through the most ventral regions of the tegmentum above, and within the substantia nigra. These axons coursed into the lateral hypothalamus adjacent to the other monoaminergic axons, and proceeded to move further lateral as they ascended rostrally. They ran through the internal capsule and projected into the caudate nucleus and putamen. A major descending periventricular catecholamine system was found in the dorsal and medial region of the tegmentum of the lower brain stem, projecting into the medulla and spinal cord. Only scattered fluorescent axons were found descending to the spinal cord through the ventral tegmentum. Other catecholamine cell groups were noted in one or more primate species; they were found within the solitary tract (i.e. group Ast), and directly beneath the aqueduct (i.e. group Aaq). The hypothalamic cell groups A11–A14 were found in the caudal hypothalamus. Except for the short projection of the arcuate nucleus (A 12) to the contact zone of the median eminence, these cells gave rise to scattered axons which formed no prominent bundles visible with fluorescence histochemistry.The serotonergic cell bodies were found in the raphe nuclei of the brain stem and adjacent tegmental fields, and gave rise to both ascending and descending pathways. Nuclei raphe obscurus (B2), pallidus (B1), and magnus (B3) gave rise to dorsal and ventral descending pathways which descended to the caudal brain stem and spinal cord in a paramedian position alongside the nuclei. Nuclei raphe ponds (B5) and dorsalis (B6, B7) gave rise to a dorsal ascending serotonergic pathway, while nucleus centralis superior (B8,B9) and associated serotonergic tegmental cells gave rise to a ventral ascending serotonergic pathway. The ascending pathways coursed through the medial forebrain bundle and further projected to numerous diencephalic and telencephalic nuclei and regions.The monoamine pathways are represented in coronal, sagittal, and horizontal sections. Although differences were noted among the species examined, the general outline of the cell groups and pathways was similar. However, the primate patterns differed in several ways from comparable systems in the rat.The local organization of primate and monoaminergic nuclei demonstrated several unique characteristics. All monoaminergic nuclei demonstrated transmitter histofluorescence in primary dendrites, and sometimes in secondary or even tertiary dendrites. Some of these dendrites formed large dendrite bundles (e.g. nuclei raphe obscurus and pallidus in the caudal medulla, nuclei raphe dorsalis and centralis superior in the rostral pons and caudal mesencephalon) which possessed dendrites from both fluorescent and non-fluorescent neurons. Smaller bundles of fluorescent dendrites also were found in the locus coeruleus (coursing across the tract of the mesencephalic nucleus of V) and in the pars reticulata of substantia nigra. Further characteristics of the dendritic arborizations of the major monoaminergic nuclei are described utilizing Golgi-Cox impregnanted material. Electron microscopic observations of the locus coeruleus, substantia nigra, and raphe nuclei revealed a direct apposition of the basement membrane of some capillaries with the plasma membrane of somas and dendrites. Golgi-Cox observations revealed tanycytes on the floor of the fourth ventricle whose shafts projected into the two major raphe dendrite bundles, locus coeruleus, and the A2 region. These observations suggest that local dendritic modulation may play an important role in the regulation of neuronal excitability of some of the monoamine cell groups, and that blood-borne or CSF-borne ligands may have ready access to receptor surfaces on some monoamine cells through the unique neuronal-vascular and tanycyte shaft relationships, respectively.Electron microscopy of the medullary and dorsal raphe nuclei, locus coeruleus, substantia nigra, and ventral tegmental area revealed the presence of numerous dendro-dendritic synapses, sometimes demonstrating membrane specializations or vesicles, but not both. Each nucleus possessed a significant population (50% or more) of cells with absent or extemely sparse axo-somatic synapses. Theses somas were invested with astrocytic processes or with extended regions of the somatic membranes of oligodendroglia. Most of the synapses on these cells were axo-dendritic or dendro-dendritic. The axo-dendritic synapses terminated on both spines and parent dendrites. Some of these neurons in the raphe nuclei were tentatively identified at the ultrastructural level as serotonergic, and in locus coeruleus as catecholaminergic, utilizing x-ray analytical electron microscopic examination of chromium-tagged, glutaraldehyde-condensed monoamines. These ultrastructural observations reinforce the important role of dendrites in these major monoaminergic nuclei for the integration of afferent information from incoming axons and from dendrites of both monoaminergic and non-monoaminergic cells.     

Afferent and efferent connections of the medial preoptic area in the rat: A WGA-HRP study

Afferent and efferent connections of the medial preoptic area including medial preoptic nucleus (MP) and periventricular area at the MP level were examined using WGA-HRP as a marker. Injections were performed by insertion of micropipette containing (1) small amount of HRP powder or (2) dryed HRP solution for 24 to 48 hr until the fixation or for 5 min respectively. Dorsal and ventral approaches of injection micropipettes were performed and the results were compared. Previously reported reciprocal connections with lateral septum, bed nucleus of the stria terminalis, medial amygdaloid nucleus, lateral hypothalamic nucleus, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus, supramammillary nucleus, central gray at the mesencephalon, raphe dorsalis, raphe medianus, and lateral parabrachial nucleus have been confirmed. In addition, we found reciprocal connections with septo-hypothalamic nucleus, amygdalo-hipocampal nucleus, subiculum, parafascicular thalamic nucleus, posterior thalamic nucleus at the caudo-ventral subdivision, median preoptic nucleus, lateral preoptic nucleus, anterior hypothalamic nucleus, periventricular area at the caudal hypothalamic level, dorsomedial hypothalamic nucleus, posterior hypothalamic nucleus, dorsal and ventral premammillary nucleus, lateral mammillary nucleus, peripeduncular nucleus, periventricular gray, ventral tegmental area, interpeduncular nucleus, nucleus raphe pontis, nucleus raphe magnus, pedunculo-pontine tegmental nucleus, gigantocellular reticular nucleus and solitary tract nucleus. The areas which had only efferent connections from MP were accumbens, caudate putamen, ventral pallidum, substantia innominata, lateral habenular nucleus, paratenial thalamic nucleus, paraventricular thalamic nucleus, mediodorsal thalamic nucleus, reuniens thalamic nucleus, median eminence, medial mammillary nucleus, subthalamic nucleus, pars compacta of substantia nigra, oculomotor nucleus, red nucleus, laterodorsal tegmental nucleus, reticular tegmental nucleus, cuneiform nucleus, nucleus locus coeruleus, and dorsal motor nucleus of vagus among which substantia innominata and median eminence were previously reported. Efferent connections to the nucleus of Darkschewitsch, interstitial nucleus of Cajal, dorsal tegmental nucleus, ventral tegmental nucleus, vestibular nuclei, nucleus raphe obsculus were very weak or abscent in the ventral approach while they were observed in dorsal approach. Previously reported afferent connections from dorsal tegmental nucleus, cuneiform nucleus, and nucleus locus ceruleus were not detected in this study.(ABSTRACT TRUNCATED AT 400 WORDS)     

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

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

Efferent connections of the habenular nuclei in the rat.

The efferent connections of the medial (MHb) and lateral (LHb) habenular nuclei in the rat were demonstrated autoradiographically following small injections of tritiated amino acids localized within various parts of the habenular complex. Comparison of individual cases led to the following conclusions. MHb efferents form the core portion of the fasciculus retroflexus and pass to the interpeduncular nucleus (IP) in which they terminate in a topographic pattern that refects 90 degrees rotations such that dorsal MHb projects to lateral IP, medial MHb to ventral, and lateral MHb to dorsal IP. Most MHb fibers cross in the interpeduncular necleus in the "figure 8" pattern described by Cajal, and terminate throughout the width of IP with only moderate preference for the ipsilateral side. However, the most dorsal part of MHb projects almost exclusively to the most lateral IP zone in a cluster pattern that is particularly dense on the ipsilateral side. The MHb appears to have no other significant projections, but very sparse MHb fibers may pass to the supracommissural septum and to the median raphe nucleus. Except for some fibers passing ventrally into the mediodorsal nucleus, all of the LHb efferents enter the fasciculus retroflexus and compose the mantle portion of the bundle. No LHb projections follow the stria medullaris. In the ventral tegmental area LHb efferents become organized into groups that disperse in several directions: (a) Rostrally directed fibers follow the medial forebrain bundle to the lateral, posterior and dorsomedial hypothalamic nuclei, ventromedial thalamic nucleus, lateral preoptic area, substantia innominata and ventrolateral septum. (b) Fibers turning laterally distribute to the substantia nigra, pars compacta (SNC); a small number continue through SNC to adjacent tegmentum. (c) The largest contingent of LHb efferents passes dorsocaudally into paramedian midbrain regions including median and dorsal raphe nuclei, and to adjacent tegmental reticular formation. Sparse addition LHb projections pass to the pretectal area, superior colliculus, nucleus reticularis tegmenti pontis, parabrachial nuclei and locus coeruleus. No LHb projections appear to involve the interpeduncular nucleus. All of these connections are in varying degree bilateral, with decussations in the supramammillary region, ventral tegmental area and median raphe nucleus. On the basis of differential afferent and efferent connections, the LHb can be divided into a medial (M-LHb) and a lateral (L-LHb) portion. The M-LHb, receiving most of its afferents from limbic regions and only few from globus pallidus, projects mainly to the raphe nuclei, while L-LHb, afferented mainly by globus pallidus and in lesser degree by the limbic forebrain, projects predominantly to a large region of reticular formation alongside the median raphe nucleus. Both M-LHb and L-LHb, however, project to SNC. The reported data are discussed in correlation with recent histochemical findings.     

Some anatomical observations on the projections from the hypothalamus to brainstem and spinal cord: an HRP and autoradiographic tracing study in the cat

The hypothalamus is closely involved in a wide variety of behavioral, autonomic, visceral, and endocrine functions. To find out which descending pathways are involved in these functions, we investigated them by horseradish peroxidase (HRP) and autoradiographic tracing techniques. HRP injections at various levels of the spinal cord resulted in a nearly uniform distribution of HRP-labeled neurons in most areas of the hypothalamus except for the anterior part. After HRP injections in the raphe magnus (NRM) and adjoining tegmentum the distribution of labeled neurons was again uniform, but many were found in the anterior hypothalamus as well. Injections of 3H-leucine in the hypothalamus demonstrated that: The anterior hypothalamic area sent many fibers through the medial forebrain bundle (MFB) to terminate in the ventral tegmental area of Tsai (VTA), the rostral raphe nuclei, the nucleus Edinger-Westphal, the dorsal part of the substantia nigra, the periaqueductal gray (PAG), and the interpeduncular nuclei. Further caudally a lateral fiber stream (mainly derived from the lateral parts of the anterior hypothalamic area) distributed fibers to the parabrachial nuclei, nucleus subcoeruleus, locus coeruleus, the micturition-coordinating region, the caudal brainstem lateral tegmentum, and the solitary and dorsal vagal nucleus. Furthermore, a medial fiber stream (mainly derived from the medial parts of the anterior hypothalamic area) distributed fibers to the superior central and dorsal raphe nucleus and to the NRM, nucleus raphe pallidus (NRP), and adjoining tegmentum. The medial and posterior hypothalamic area including the paraventricular hypothalamic nucleus (PVN) sent fibers to approximately the same mesencephalic structures as the anterior hypothalamic area. Further caudally two different fiber bundles were observed. A medial stream distributed labeled fibers to the NRM, rostral NRP, the upper thoracic intermediolateral cell group, and spinal lamina X. A second and well-defined fiber stream, probably derived from the PVN, distributed many fibers to specific parts of the lateral tegmental field, to the solitary and dorsal vagal nuclei, and, in the spinal cord, to lamina I and X, to the thoracolumbar and sacral intermediolateral cell column, and to the nucleus of Onuf. The lateral hypothalamic area sent many labeled fibers to the lateral part of the brainstem and many terminated in the caudal brainstem lateral tegmentum, including the parabrachial nuclei, locus coeruleus, nucleus subcoeruleus, and the solitary and dorsal vagal nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)     

Efferent connections of the substantia nigra and ventral tegmental area in the rat

Small injections of tritiated leucine and proline confined to the ventral tegmental area (AVT) were found to label fibers ascending: (a) to the entire ventromedial half of the striatum, but most massively to the ventral striatal zone that includes the nucleus accumbens; (b) to the thalamus: lateral habenular nucleus, nuclei reuniens and centralis medius, and the most medial zone of the mediodorsal nucleus; (c) to the posterior hypothalamic nucleus and possibly the lateral hypothalamic and preoptic region; (d) to the nuclei amygdalae centralis, lateralis and medialis; (e) to the bed nucleus of the stria terminalis, the nucleus of the diagonal band, and the medial half of the lateral septal nucleus; (f) to the anteromedial (frontocingulate) cortex; and (g) to the entorhinal area. Further AVT efferents descend to the medial half of the midbrain tegmentum including an anterior region of the median raphe nucleus, to the ventral half of the central grey substance including the dorsal raphe nucleus, to the parabrachial nuclei, and to the locus coeruleus. Similar injections centered in the pars compacta of the substantia nigra (SNC) label fibers that are distributed in the striatum in an orderly medial-to-lateral arrangement, and almost entirely avoid the nucleus accumbens and olfactory tubercle. With the exception of the lateral quarter of the substantia nigra, which apparently does not project to the extreme rostral pole of the striatum, each small SNC locus, regardless of its anteroposterior localization, distributes nigrostriatal fibers throughout the length of the striatum. Descending SNC efferents are distributed to the same general regions that receive descending AVT projections, except that no SNC fibers appear to enter the locus coeruleus. Isotope injections confined to the pars reticulata (SNR) label sparse nigrostriatal fibers, and numerous nigrothalamic fibers ascending mainly to the nucleus ventromedialis and in lesser number to the parafascicular nucleus and the paralamellar zone of the nucleus mediodorsalis. Descending SNR fibers leave the nigra as a voluminous fiber bundle that bifurcates into a large nigrotectal and a smaller nigrotegmental component, the latter terminating largely in the pedunculopontine nucleus of the pontomesencephalic tegmentum.     

The connections of the septal region in the rat

The efferent, afferent and intrinsic connections of the septal region have been analyzed in the rat with the autoradiographic method. The lateral septal nucleus, which can be divided into dorsal, intermediate and ventral parts, receives its major input from the hippocampal formation and projects to the medial septal-diagonal band complex. The ventral part of the nucleus also sends fibers through the medial forebrain bundle to the medial preoptic and anterior hypothalamic areas, to the lateral hypothalamic area and the dorsomedial nucleus, to the mammillary body (including the supramammillary region), and to the ventral tegmental area. The medial septal nucleus/diagonal band complex projects back to the hippocampal formation by way of the dorsal fornix, fimbria, and possibly the cingulum. Both nuclei also project through the medial forebrain bundle to the medial and lateral preoptic areas, to the lateral hypothalamic area, and to the mammillary complex. The medial septal nucleus also sends fibers to the midbrain (the ventral tegmental area and raphe nuclei) and to the parataenial nucleus of the thalamus, while the nucleus of the diagonal band has an additional projection to the anterior limbic area. Ascending inputs to the medial septal nucleus/diagonal band complex arise in several hypothalamic nuclei and in the brainstem aminergic cell groups. The posterior septal nuclei (the septofimbrial and triangular nuclei) receive their major input from the hippocampal formation, and project in a topographically ordered manner upon the habenular nuclei and the interpeduncular nuclear complex. The bed nucleus of the stria terminalis receives its major input from the amygdala (Krettek and Price, '78); but other afferents arise from the ventral subiculum, the ventromedial nucleus, and the brainstem aminergic cell groups. The principal output of the bed nucleus is through the medial forebrain bundle to the substantia innominata, the nucleus accumbens, most parts of the hypothalamus and the preoptic area, the central tegmental fields of the midbrain, the ventral tegmental area, the dorsal and median nuclei of the raphe, and the locus coeruleus. The bed nucleus also projects to the anterior nuclei of the thalamus, the parataenial and paraventricular nuclei, and the medial habenular nucleus, and through the stria terminalis to the medial and central nuclei of the amygdala, and to the amygdalo-hippocampal transition area.     

ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean zucker rats

The binding sites of nociceptin (also named orphanin FQ), the endogenous ligand of ORL1 (opiate receptor like 1), were localized in rat brain, using an autoradiographic procedure. High levels of binding were observed in the cingulate, retrosplenial, perirhinal, insular and occipital cortex, anterior and posteromedial cortical amygdaloid nuclei, basolateral amygdaloid nucleus, amygdaloid complex, posterior hippocampus, dorsal endopiriform, central medial thalamic, paraventricular, rhomboid thalamic, suprachiasmatic, ventromedial hypothalamic nuclei, mammillary complex, superficial gray layer of the superior colliculus, locus coeruleus, dorsal raphe nucleus. More moderate labelling was observed in the prefrontal, fronto–parietal, temporal, piriform cortex, dentate gyrus, anterior olfactory nucleus, olfactory tubercle, shell of nucleus accumbens, claustrum, lateral septum, laterodorsal thalamic, medial habenular, subthalamic, reuniens thalamic nuclei, subiculum, periaqueductal grey matter and pons. A lower binding site density was observed in the anterior and medial hippocampus, olfactory bulb, caudate putamen, the core of the nucleus accumbens, medial septum, ventrolateral, ventroposterolateral and mediodorsal thalamic nuclei, lateral and medial geniculate nuclei, hypothalamic area, substantia nigra, ventral tegmentum area and interpedoncular nucleus. A moderate and similar labelling was found in the dorsal and ventral horn of the spinal cord. No labelling was apparent in the corpus callosum. Thus, it appears that the ORL1 receptor is particularly abundant in the cerebral cortex, limbic system of the rat brain and some areas involved in pain perception.     

Afferent connections of the striatum and the nucleus accumbens in the lizard Gekko gecko

The afferent connections of the striatum and the nucleus accumbens of the lizard Gekko gecko were studied with retrograde tracing by means of horseradish peroxidase and Fluoro-Gold and with anterograde tracing by means of Phaseolus vulgaris leukoagglutinin. The striatum receives projections from the cortex, the dorsal ventricular ridge, the lateral amygdaloid nucleus, the globus pallidus, the anterior peduncular nucleus, the ventral tegmental area and substantia nigra, the area ventral to the substantia nigra, and the dorsal thalamus. The nucleus accumbens is projected upon by the cortex, the diagonal band, the ventral pallidum, the lateral preoptic area, the ventral tegmental area, and the dorsal thalamus. The source of the cortical projection to the striatum and the nucleus accumbens is a longitudinal zone in the dorsal cortex that, rostrally in the hemisphere, is located medially and, more caudally, in its middle one third. The medial and rostrolateral areas of the dorsal ventricular ridge each project to the striatum in a vertical zone. The fibers from the caudolateral area of the ridge end in two oblique bands located parallel to the border between the dorsal ventricular ridge and the striatum. The pathways from the mesencephalic tegmentum to the striatum and the nucleus accumbens show a medial to lateral topography. This is similar to the situation in birds, but contrary to that in mammals in which these pathways are extensively interconnected. The specific sensory nuclei of the dorsal thalamus were found to project not only to the dorsal ventricular ridge, but also, and in a topographical fashion, to the striatum. The dorsomedial thalamic nucleus, which innervates the dorsal ventricular ridge, has additional projections to the striatum and the nucleus accumbens. This projection pattern is similar to that of the intralaminar thalamic nuclei of birds and mammals.     

An HRP study of the afferent connections to rat lateral hypothalamic region

Afferent connections to the lateral hypothalamic region in the rat were studied using horseradish peroxidase (HRP). HRP was injected iontophoretically by a parapharyngeal approach. After HRP injections into the lateral hypothalamic area, labeled cells were found mainly in the medial prefrontal and infralimbic cortices, lateral and dorsal septal nuclei, nucleus accumbens, bed nucleus of the stria terminalis, medial and lateral amygdaloid nuclei, lateral habenular nucleus, peripeduncular nucleus, ventral tegmental area, mesencephalic and pontine central gray, ventral nucleus of the lateral lemniscus, lateral parabrachial area, raphe nuclei and the nucleus locus coeruleus. Labeled cells following HRP injections into the lateral preoptic area were found mainly in the lateral and dorsal septal nuclei, nucleus accumbens, diagonal band, ventral part of the globus pallidus, bed nucleus of the stria terminalis, central amygdaloid nucleus, mesencephalic and pontine central gray, dorsal raphe nucleus, parabrachial area and the nucleus locus coeruleus. The intrahypothalamic connections were also discussed.     

Histochemical mapping of dopamine neurons and fiber pathways in dog mesencephalon

A topographic mapping of dopamine (DA)-containing neurons and fibers was done mainly in the mesencephalon of the dog using the fluorescent histochemical technique of Falck and Hillarp. The extensive DA neuron system was found to be located in the ventral and medial regions of the mesencephalon; the pars compacta of the substantia nigra, the area almost corresponding to the ventral tegmental area of Tsai (hich consists of three groups, a caudal, the nucleus parabrachialis pigmentosus, a ventral, the nucleus paranigralis and a rostral, the caudal part of the nucleus tegmentalis gventralis of Tsai), the nucleus linearis of the raphe, and the mesencephalic reticular formation. The nigro-neostriatal projection can be traced in the non-treated or nialamide plus L-dopa treated puppies without the lesion-degeneration technique. Most fibers arising from these DA cell groups assemble at the prerubral area and ascend just dorsal to the medial forebrain bundle. Most fibers turn laterally at the lateral hypothalamus and enter the neostriatum via the dorsal part of the subthalamic nucleus, the zona incerta and the capsula interna. These findings show that the distribution of DA neurons and the nigro-neostriatal pathway are fundamentally similar to those in other mammals. In this study, the processes of the nigral and paranigral DA neurons have been demonstrated to project into the pars reticulata in the dog.     

Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study.

The ascending projections of the locus coeruleus were studied using an autoradiographic method. The major projection of locus coeruleus neurons ascends in a dorsal pathway traversing the midbrain tegmentum in a position ventrolateral to the periaqueductal gray. At the caudal diencephalon the locus coeruleus axons descend to enter the medial forebrain bundle at a caudal tuberal hypothalamic level. They are jointed in the medial forebrain bundle by a much smaller locus coeruleus projection which takes a ventral course through the midbrain tegmentum and enters the medial forebrain bundle via the mammillary peduncle and ventral tegmental area. Terminal projections are evident in the midbrain to the periaqueductal gray, tegmentum and raphe nuclei. There are widespread projections to the dorsal thalamus. The heaviest of these are to the intralaminar nuclei, the anteroventral and anteromedial nuclei, the dorsal lateral geniculate and the paraventricular nucleus. In the hypothalamus the largest projections are to the lateral hypothalamic area, periventricular nucleus, supraoptic nucleus and paraventricular nucleus. As the locus coeruleus projection ascends in the medial forebrain bundle, fibers leave it to traverse the lateral hypothalamus and zona incerta and enter the internal capsule, the ventral amygdaloid bundle and ansa peduncularis. These appear to terminate in the amygdaloid complex and, via the external capsule, in the lateral and dorsal neocortex. At the level of the septum 4 projections are evident. One group of fibers enters the stria medullaris to terminate in the paraventricular nucleus and habenular nuclei. A second group joins the stria terminalis to terminate in the anygdaloid complex. The third group turns into the diagonal band and medial septum; some fibers terminate in the septal nuclei and others continue into the fornix to termimate in hippocampus. A large component continues around the corpus callosum into the cingulum to terminate in the cingulate and adjacent neocortex, the subiculum and hippocampus. The remaining fibers continue rostrally in the medial forebrain bundle to terminate in olfactory forebrain and frontal neocortex. Commissural projections arise at 4 locations. The first decussation occurs in the dorsal tegmentum just below the central gray rostral to the locus coeruleus. The crossing fibers enter the contralateral dorsal bundle. A second group of fibers leaves the ipsilateral dorsal pathway, crosses in the posterior commissure and enters the contralateral dorsal pathway at the level. The third commissural projection arises more rostrally and crosses in the dorsal supraoptic commissure to enter the contralateral medial forebrain bundle. The fourth commissural projection is through the anterior commissure. The termination of the contralateral projection appears similar to that of the ipsilateral projection.     

Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata

The infralimbic area (IL) and prelimbic area (PL) have been postulated as an autonomic motor region in the medial prefrontal cortex. The present study was conducted to reveal the projection sites of IL and PL of the monkey, Macaca fuscata, using biotinylated dextran amine as an anterograde tracer. IL and PL projected densely to the ventromedial caudate nucleus, the core and shell of the nucleus accumbens (Acb), parvicellular lateral basal and magnocellular accessory basal nuclei of the amygdala, lateral preoptic area, ventromedial hypothalamic nucleus, tubero-mammillary nucleus (TM), medial part of the magnocellular and dorsal part of the parvicellular (MDpc) dorsomedial thalamic nuclei, reunience and medial part of the medial pulvinar nucleus, and dorso-lateral part of the periaqueductal gray (PAGdl) in the mesencephalon. Moderately to weakly projected areas were the intermediate and lateral parts of the agranular insular cortex, orbital part of area 12, agranular and dysgranular part of the temporal pole cortex (TPa-g), auditory temporal cortex, lateral and medial (MS) septal nuclei, bed nucleus of the stria terminalis, diagonal band of Broca, substantia innominata, and medial preoptic area, dorsomedial, lateral, and posterior hypothalamic nuclei, magnocellular lateral basal and lateral amygdaloid nuclei, paratenial, paraventricular (PV), inter-antero-medial (IAM), reticular, central medial (CeM), parafascicular (PF) and limitans nuclei of the thalamus, lateral habenular nucleus, pedunculo-pontine nucleus, dorsal part of the lateral lemniscal nucleus, ventral tegmental area (VTA), dorsal raphe, superior central nucleus, medial and lateral parabrachial nuclei (PBl) and nucleus locus coeruleus (LC). A few scattered terminals were observed in the perifornical nucleus of the hypothalamus and substantia nigra pars compacta. PL and area 24 were characterized by projections to the entorhinal (Ent) and piriform (Pir) cortex as well as to the magnocellular part of the ventral anterior thalamic nucleus (VAmc). The morphology of the terminal arborization in each nuclei was different in appearance, perhaps reflecting the synaptic interaction between the nerve terminals and postsynaptic dendrites. PL projected uniquely to Ent, Pir and VAmc and IL projected uniquely to TPa-g, MS, IAM, CeM, MDpc, PF, PBl and LC. IL projected more strongly than PL to the shell of Acb, amygdaloid nuclei, PV, TM, VTA and PAGdl. The present results support the hypothesis that IL is a major cortical autonomic motor area and PL integrates limbic and autonomic inputs in the primate.     

Brainstem innervation of prefrontal and anterior cingulate cortex in the rhesus monkey revealed by retrograde transport of HRP

The cells of origin of projections from the brainstem to the dorsolateral and orbital prefrontal granular cortex and to the anterior cingulate cortex of the rhesus monkey were analyzed by means of retrograde axonal transport of the enzyme horseradish peroxidase (HRP). Following injections in various portions of the dorsolateral prefrontal and in the cingulate cortex, HRP-positive neurons were found in three main locations: (1) the ventral midbrain including the anterior ventral tegmental area, the medial one-third of the substantia nigra pars compacta, and the retrorubral nucleus; (2) the central superior nucleus and the dorsal raphe nucleus, primarily in its caudal subdivision; and (3) the locus coeruleus and adjacent medial parabrachial nucleus. Labeled neurons in the raphe nuclei and locus coeruleus were distributed bilaterally. A basically similar pattern of labeled somata was found in the brainstem with HRP injections in the orbital prefrontal cortex. Scattered HRP-positive cells were found throughout the ipsilateral ventral tegmental area and in ventromedial portions of the retrorubral nucleus, and a large number of HRP-positive cells were distributed bilaterally in the dorsal raphe and central superior nuclei as well as the dorsolateral pontine tegmentum. However, in contrast to the results obtained with injections on the dorsolateral and medial aspects of the hemisphere, labeled neurons were not found in any portion of the substantia nigra. The neurons labeled retrogradely after injection of HRP in these various regions of the frontal lobe in rhesus monkey correspond both in location and morphology to the monoamine-containing neurons of the brainstem and are thus very likely the source of dopamine, norepinephrine, and serotonin found in the frontal cortex of the same species.     

Afferent connections of septal nuclei of the domestic chick (Gallus domesticus): a retrograde pathway tracing study

The afferents to the septum of the domestic chicken were studied using retrograde tracers, rhodamine conjugated latex bead or Fast Blue, placed in different septal subregions. The results were verified by anterograde tracer injections deposited to selected areas. The main telencephalic afferents to the septum arise ipsilaterally from the hippocampal formation, dorsolateral corticoid area, piriform cortex, amygdaloid pallium, and the ventral pallidum. Contralateral afferents originate from the lateral septum and the amygdaloid pallium. A massive bilateral projection arises from the lateral hypothalamus. Other hypothalamic afferents arise from the periventricular, paraventricular and anterior medial nuclei, and the premammillary and mammillary areas. The dorsal thalamic nuclei (dorsal medial anterior and posterior) and the reticular dorsal nuclei also contribute septal afferents. Brainstem afferents arise bilaterally from the ventral tegmental area, substantia nigra, central gray, A8, locus coeruleus, ventral subcoeruleus nucleus, and raphe nuclei. The main terminal fields for septal afferents lie in the lateral septal nucleus and the belt of medial septal nucleus. The core of the latter is invaded mainly by fibers from the brainstem, presumably belonging to the ascending activating system. The septal afferents of the chicken are largely similar to those of other avian and nonavian species. The most prominent differences with previous pigeon data were found in the subregional selectivity of the hippocampal formation, dorsolateral corticoid area, mammillary nuclei, some dorsal thalamic nuclei, substantia nigra, and subcoeruleus nuclei in their projections to defined septal nuclei.     

Brainstem afferents to the magnocellular basal forebrain studied by axonal transport, immunohistochemistry, and electrophysiology in the rat

Brainstem afferents to the magnocellular basal forebrain were studied by using tract tracing, immunohistochemistry and extracellular recordings in the rat. WGA-HRP injections into the horizontal limb of the diagonal band (HDB) and the magnocellular preoptic area (MgPA) retrogradely labelled many neurons in the pedunculopontine and laterodorsal tegmental nuclei, dorsal raphe nucleus, and ventral tegmental area. Areas with moderate numbers of retrogradely labelled neurons included the median raphe nucleus, and area lateral to the medial longitudinal fasciculus in the pons, the locus ceruleus, and the medial parabrachial nucleus. A few labelled neurons were seen in the substantia nigra pars compacta, mesencephalic and pontine reticular formation, a midline area in the pontine central gray, lateral parabrachial nucleus, raphe magnus, prepositus hypoglossal nucleus, nucleus of the solitary tract, and ventrolateral medulla. A similar but not identical distribution of labelled neurons was seen following WGA-HRP injections into the nucleus basalis magnocellularis. The possible neurotransmitter content of some of these afferents to the HDB/MgPA was examined by combining retrograde Fluoro-Gold labelling and immunofluorescence. In the mesopontine tegmentum, many retrogradely labelled neurons were immunoreactive for choline acetyltransferase. In the dorsal raphe nucleus, some retrogradely labelled neurons were positive for serotonin and some for tyrosine hydroxylase (TH); however, the majority of retrogradely labelled neurons in this region were not immunoreactive for either marker. The ventral tegmental area, substantia nigra pars compacta, and locus ceruleus contained retrogradely labelled neurons which were also immunoreactive for TH. Of the retrogradely labelled neurons occasionally observed in the nucleus of the solitary tract, prepositus hypoglossal nucleus, and ventrolateral medulla, some were immunoreactive for either TH or phenylethanolamine-N-methyltransferase. To characterize functionally some of these brainstem afferents, extracellular recordings were made from antidromically identified cortically projecting neurons, mostly located in the HDB and MgPA. In agreement with most previous studies, about half (48%) of these neurons were spontaneously active. Electrical stimulation in the vicinity of the pedunculopontine tegmental and dorsal raphe nuclei elicited either excitatory or inhibitory responses in 21% (13/62) of the cortically projecting neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Differential projections of habenular nuclei

Lesions were made in the lateral and medial habenular nuclei of the cat. Subsequent degeneration of nerve fibers and terminalis was studied using Nauta-Gygax silver technique. The medial and lateral habenular nuclei project differentially to the septum, olfactory, tubercle, thalamus, midbrain tegmentum and tectum. The diffuse part of the habenulopeduncular tract rises from the lateral habenular nucleus and the compact part rises from both nuclei. Degenerating terminals were seen caudally in the following nuclei: interpeduncular, central superior, dorsal raphae, ventral tegmental (from the medial habenular nucleus), dosral tegmental (from the lateral habenular nucleus), pretectal area, superior colliculus and inferior colliculus (from the lateral habenular nucleus). Rostral projections course in the medial part of the stria medullaris from the medial habenular nucleus and in the lateral part of the stria medullaris from the lateral habenular nucleus: Degenerating terminals were seen rostrally in the following nuclei: dorsomedial, anteroventral, anterodorsal, paraventricular, posterior medial septal (from the medial habenular nucleus) and preoptic area (from the lateral habenular nucleus). Projections occur from the medial habenular nucleus to the amygdala via the stria terminalis. The habenular nuclei are considered to be structures of the limbic system which are differentially related to midbrain, thalamic, amygdaloid, septal and preoptic structures via feedback circuits.