Ascending projections from the pedunculopontine tegmental nucleus and the adjacent mesopontine tegmentum in the rat

Ascending projections from the pedunculopontine tegmental nucleus (PPT) and the surrounding mesopontine tegmentum to the forebrain in the rat are here examined by using both retrograde and anterograde tracing techniques combined with choline acetyltransferase (ChAT) immunohistochemistry. The anterogradely transported lectin Phaseolus vulgaris-leukoagglutinin (PHA-L) was iontophoretically injected into the PPT in 12 rats. Anterogradely labelled fibers and varicosities were observed in the thalamic nuclei, confirming the findings of our previous retrograde studies (Hallanger et al: J. Comp. Neurol. 262:105-124, '87). In addition, PHA-L-labelled fibers and varicosities suggestive of terminal fields were observed in the anterior, tuberal, and posterior lateral hypothalamic regions, the ventral pallidum in the region of the nucleus basalis of Meynert, the dorsal and intermediate lateral septal nuclei, and in the central and medial nuclei of the amygdala. To determine whether these were cholinergic projections, the retrograde tracer WGA-HRP was injected into terminal fields in the hypothalamus, septum, ventral pallidum, and amygdala. Numerous ChAT-immunoreactive neurons in the PPT and laterodorsal tegmental nucleus (LDT) were retrogradely labelled from the lateral hypothalamus. These cholinergic neurons constituted over 20% of those retrogradely labelled in the dorsolateral mesopontine tegmentum; the balance consisted of noncholinergic neurons of the central tegmental field, retrorubral field, and cuneiform nucleus. Following placement of WGA-HRP into dorsal and intermediate lateral septal regions, the vast majority (greater than 90%) of retrogradely labelled neurons were cholinergic neurons of the PPT and LDT, with few noncholinergic retrogradely labelled neurons in the adjacent tegmentum. In contrast, fewer cholinergic neurons were retrogradely labelled following placement of tracer into the nucleus basalis of Meynert or into the central, medial, and basolateral nuclei of the amygdala, while numerous noncholinergic neurons of the central tegmental field rostral to the PPT and of the retrorubral field adjacent to the PPT were retrogradely labelled in these cases. These anterograde and retrograde studies demonstrate that cholinergic PPT and LDT neurons provide a substantial proportion of mesopontine tegmental afferents to the hypothalamus and lateral septum, while projections to the nucleus basalis and the amygdala are minimal.     

Topography and synaptology of mamillary body projections to the mesencephalon and pons in the rat.

The anterograde and retrograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) was used to study the anatomical organization of descending projections from the mamillary body (MB) to the mesencephalon and pons at light and electron microscopic levels. Injections of WGA-HRP into the medial mamillary nucleus resulted in dense anterograde and retrograde labeling in the ventral tegmental nucleus, while injections in the lateral mamillary nucleus resulted in dense anterograde labeling in the dorsal tegmental nucleus pars dorsalis and dense anterograde and retrograde labeling in the pars ventralis of the dorsal tegmental nucleus. Anterogradely labeled fibers in the mamillotegmental tract diverged from the principal mamillary tract in an extensive dorsocaudally oriented swath of axons which extended to the dorsal and ventral tegmental nuclei, and numerous axons turned sharply ventrally and rostrally to terminate topographically in the dorsomedial nucleus reticularis tegmenti pontis and rostromedial pontine nuclei. The anterograde labeling in these two precerebellar relay nuclei was distributed near the midline such that projections from the lateral mamillary nucleus terminated mainly dorsomedial to the terminal fields of projections from the medial mamillary nucleus. In the dorsal and ventral tegmental nuclei, labeled axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions primarily with small diameter dendrites and to a lesser extent with neuronal somata. A few labeled terminals contained pleomorphic vesicles and formed symmetric synaptic junctions with dendrites and neuronal somata. Labeled axon terminals were also frequently found in synaptic contact with retrogradely labeled dendrites and neuronal somata in the dorsal and ventral tegmental nuclei. These findings indicate that neurons in the dorsal and ventral tegmental nuclei are reciprocally connected with MB projection neurons. In the nucleus reticularis tegmenti pontis and medial pontine nuclei, labeled axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions primarily with small diameter dendrites. The present study demonstrates that projections from the medial and lateral nuclei of the MB are topographically organized in the mesencephalon and pons. The synaptic morphology of mamillotegmental projections suggests that they may have excitatory influences primarily on the distal dendrites of neurons in these brain regions.     

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.     

Failure of amygdaloid lesions to increase the threshold for self-stimulation of the lateral hypothalamus and ventral tegmental area

It has been proposed that the directly stimulated axons underlying the rewarding effect of medial forebrain bundle (MFB) stimulation originate in the forebrain and descend at least as far as the ventral tegmentum. However, little is known about the location of the somata that give rise to these axons. Among the nuclei that contribute fibers to the descending component of the MFB and project past the lateral hypothalamus (LH) and ventral tegmental area (VTA) are cell groups within the amygdaloid complex. In this study, the rewarding effectiveness of stimulating the LH and VTA was measured before and after the amygdaloid complex was damaged by electrolytic lesions. Changes in rewarding effectiveness were inferred from shifts in the frequency required to sustain a half-maximal rate of lever-pressing at each of 3 currents. Following the lesions, there was no clear evidence of substantial, sustained decreases in rewarding effectiveness at the 14 stimulation sites, although one subject ceased to self-stimulate reliably. Given that the lesions damaged the principal amygdaloid sources of descending MFB fibers, these results suggest that the amygdaloid complex is not a major source of the directly activated fibers responsible for the rewarding effect of MFB stimulation.     

Efferent projections from the mammillary complex of the guinea pig: an autoradiographic study

The efferent projections from the medial and lateral mammillary nuclei of the guinea pig were traced after injecting tritiated amino acid. The major efferent started as the principal mammillary tract, but soon divided into mammillothalamic and mammillotegmental tracts. The mammillothalamic tract projected anterodorsally and terminated in the anterior dorsal, anterior ventral and anterior medial thalamic nuclei. The mammillotegmental tract projected caudally and terminated in the dorsal tegmental nucleus and central gray. The mammillary efferents in the mammillary peduncle ran via the tegmentum of the midbrain and pons. It terminated in the dorsal and ventral tegmental nuclei, basal pontine nucleus and pontine tegmental reticular nucleus. A diffuse mammillary projection had fibers directed dorsally which distributed in the midline thalamic nuclei and in central gray. Rostral projections via the medial forebrain bundle from the medial mammillary nucleus were found in the septal area and diagonal band of Broca. The lateral mammillary nucleus sent fibers which also joined the mammillothalamic and mammillotegmental tracts. These terminated bilaterally mainly in the anterior dorsal and anterior ventral nuclei of the thalamus, and caudally in the dorsal and ventral tegmental nuclei and basal pontine nucleus.     

Efferent connections of the lateral hypothalamic area of the rat: An autoradiographic investigation

The efferent projections of the lateral hypothalamic area (LHA) at mid-tuberal levels were examined with the autoradiographic tracing method. Connections were observed to widespread regions of the brain, from the telencephalon to the medulla. Ascending fibers course through LHA and the lateral preoptic area and lie lateral to the diagonal band of Broca. Fibers sweep dorsally into the lateral septal nucleus, cingulum bundle and medial cortex. Although sparse projections are found to the ventromedial hypothalamic nucleus, a prominent pathway courses to the dorsal and medial parvocellular subnuclei of the paraventricular nucleus. Labeled fibers in the stria medullaris project to the lateral habenular nucleus. The central nucleus of the amygdala is encapsulated by fibers from the stria terminalis and the ventral amygdalofugal pathway. The substantia innominate, nucleus paraventricularis of the thalamus, and bed nucleus of the stria terminalis also receive LHA fibers. Three descending pathways course to the brainstem: (1) periventricular system, (2) central tegmental tract (CTT), and (3) medial forebrain bundle (MFB). Periventricular fibers travel to the ventral and lateral parts of the midbrain central gray, dorsal raphe nucleus, and laterodorsal tegmental nucleus of the pens. Dorsally coursing fibers of CTT enter the central tegmental field and the lateral and medial parabrachial nuclei. The intermediate and deep layers of the superior colliculus receive some fibers. Fibers from CTT leave the parabranchial region by descending in the ventrolateral pontine and medullary reticular formation; some of these fibers sweep dorsomedially into the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and nucleus commissuralis. From MFB, fibers descend into the ventral tegmental area and to the border of the median raphe and raphe magnus nuclei.     

Cerebellar pathways to ventral midbrain and nigra

This study on cat and rat indicates that the cerebellar nuclei connect with a continuum of cells located on either side of midline in the ventral tegmentum of the midbrain. The following nuclei are located within this region: nigra, ruber, interpeduncularis, ventral tegmental (Tsai), and linearis rostralis. The nucleus fastigii projection is primarily ipsilateral to this region by way of a mediaal and dorsal pathway (accessory brachium conjunctivum). A greater number of these fibers terminates in medial as contrasted to lateral structures. The projections of nuclei interpositus-dentatus are primarily contralateral and become part of a lateral and ventral pathway through the brachium conjunctivum. Reduced-silver methods and horseradish peroxidase-treated materials furnish some evidence for a small Purkinje cell connection directly to the ventral tegmental area. Biochemical studies on dopamine levels in the forebrain indicate there is an increase ipsilateral to the cerebellar cortical lesion whereas a lesion in nucleus fastigii results in a decrease of dopamine levels in ipsilateral forebrain. Some cerebellar influences on catecholamine systems are discussed.     

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.     

Catecholaminergic systems in the zebrafish. II. Projection pathways and pattern of termination of the locus coeruleus

The locus coeruleus is a widely projecting isthmal noradrenergic nucleus. In the zebrafish, it consists of between three and ten neurons, most of which have multiple, bilaterally projecting axons. Immunohodolgical studies show that the locus coeruleus provides most, if not all, of the noradrenergic innervation of the brain rostral to the isthmus. The pathways and targets in the zebrafish are similar to ascending coeruleal projections of other vertebrates. Axons ascend through two amin pathways: the longitudinal catecholamine bundle and the periventricular catecholamine pathway. The former is a dense meshwork of varicosity-bearing axons which ascends along the lateral longitudinal fasciculus into the mesencephalon. In the posterior tuberal area, this bundle dives ventrally and assumes a lateral position. In the diencephalon, it takes up a position ventral to the medial forebrain bundle, and follows this bundle into the telencephalon, where it joins the medial olfactory tract to enter the olfactory bulb. The periventricular catecholamine pathway is a diffuse pathway consisting of thick, smooth axons. It is associated with the medial longitudianl fasciculus. Rostral to the nucleus of the medial longitudinal fasciculus, this pathway joins the longitudinal catecholamine bundle around the medial forebrain bundle. The Periventricular pathway gives rise to coarse terminal arbors with large but sparse varicosities, whereas the longitudinal catecholamine bundle gives rise to terminal plexuses with fine and dense fibers and varicosities. Among the more densely innervated regions are the raphé nucleus, the interpeduncular nucleus, the torus semicircularis, parts of the hypothalamus, and the suprachiasmatic and preoptic areas. The tours longitudinalis, optic tectum, cerebellum, habenular complex, the dorsomedial zone of area dorsalis telencephali, and the olfactory bulb are moderately innervated. The nucleus glomerulosus, the torus lateralis and lateral subnuclei of the nucleus diffusus, and the anterior tuberal nucleus are devoid of noradrenergic innervation. © 1994 Wiley-Liss, Inc.     

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.     

Efferent projections from the paraventricular nucleus mediating alpha 2-noradrenergic feeding

Feeding behavior elicited by central injection of the alpha-noradrenergic agonists, norepinephrine (NE) and clonidine (CLON), are believed to be mediated via postsynaptic alpha 2-type receptors located in the paraventricular nucleus (PVN). To map the course taken by essential efferent (descending) fibers of this PVN system for noradrenergically-stimulated feeding, the impact of diencephalic and lower brainstem coronal knife cuts, on the responses elicited by PVN-injected NE and CLON, was assessed. Rats that sustained damage in the periventricular gray area of the caudal thalamus and midbrain exhibited significant losses in feeding elicited by PVN injections of these drugs. In the case of animals with midbrain periventricular gray knife cuts, a significant increase in daily food intake was also observed, and this increase was positively correlated in magnitude with the attenuation of NE-induced feeding. This decrease in sensitivity to alpha 2-noradrenergic stimulation occurred with discrete periventricular knife cuts extending only 0.5 mm lateral to midline. In contrast, large ventral or lateral coronal knife cuts throughout the dorsal and ventral midbrain tegmentum left intact NE- and CLON-induced feeding. These findings provide evidence for localization of anatomical substrates which underlie PVN alpha 2-noradrenergic feeding. The efferent fibers of this system appear to exit from the PVN in a dorsomedial direction and course through the thalamic periventricular area. As this projection descends into the midbrain, it remains quite medial, maintaining this position throughout the midbrain central gray substance. At the level of the pons, just rostral to the locus coeruleus, this fiber projection appears to course ventrolaterally into the dorsolateral pontine tegmentum and possibly continue towards the dorsal vagal complex of the dorsomedial medulla.     

Postmortem anterograde tracing of intrahypothalamic projections of the human dorsomedial nucleus of the hypothalamus

Together with the paraventricular nucleus (PVN), the dorsomedial nucleus of the hypothalamus (DMH) acts as one of the hypothalamic centers that integrate autonomic and central information. The DMH in the rat brain has extensive intrahypothalamic connections and is implicated in a wide variety of functions. Up until now, no knowledge has been available to indicate that the human DMH might have functions similar to those of the rat DMH. In the present study, intrahypothalamic efferent projections of the human DMH were revealed by a recently developed in vitro postmortem tracing method. It was found that the most densely innervated areas are the PVN, the ventromedial nucleus of the hypothalamus, and the area below the PVN. Other significant terminal fields include the periventricular nucleus, the lateral hypothalamic area, and the medial part of the anteroventral hypothalamic area. Scarce fibers project to the suprachiasmatic nucleus, infundibular nucleus, posterior hypothalamic nucleus, and posterior part of the bed nucleus of the stria terminals. The projections of the ventral and dorsal part of the DMH show some differences. The dorsal part of the DMH has denser projections to the dorsal part of the PVN than to the ventral part of the PVN. In contrast, the ventral part of the DMH has denser projections to the ventral part of the PVN. Labeled fibers in the PVN from ventral and dorsal DMH appear to run near many vasopressin and oxytocin neurons of different sizes, and also near some corticotropin- releasing hormone neurons, suggesting that the DMH neurons may directly affect the functioning of these PVN neurons. In many aspects, the observed projections of the human DMH resemble those of the rat, indicating that the organization of DMH intrahypothalamic projections of human is similar to that of rat. The functional significance of DMH intrahypothalamic connections is discussed. J. Comp. Neurol. 401:16–33, 1998. © 1998 Wiley-Liss, Inc.     

Enhanced binocular interaction in the visual cortex of normal kittens subjected to intracortical norepinephrine perfusion

Immunoreactive fibers and varicosities in the hypothalamic paraventricular nucleus (PVN) were examined by light- and electronmicroscopy, following treatment of brain slices with specific antibodies to adrenocorticotropin (ACTH), beta-endorphin (beta-End) and alpha-melanotropin (alpha-MSH) peptides. In an attempt to provide a more precise, quantitative definition of the densities of immunoreactive elements, sections were analyzed by computer based image-analysis techniques. Fibers and varicosities immunostained with the 3 different antibodies displayed an identical distribution pattern throughout the nucleus suggesting that they are parts of the same, arcuate pro-opiomelanocortin (POMC) neuron system. Although immunoreactive varicosities were found all over the PVN, it was possible to identify a characteristic, density distribution pattern. At the ultrastructural level, immunoreactive presynaptic nerve terminals were observed forming symmetrical synaptic contacts with unlabeled dendrites. The majority of immunoreactive elements were found in the dorsal parvo- and caudal magnocellular subdivisions which give rise to long projections to the lower brainstem. Moderate density of POMC neural elements was observed in the anterior and medial (ventral portion) parvocellular subdivisions which project to the external zone of the median eminence. Only a few, widely scattered immunostained varicosities are found in the medial and lateral magnocellular subdivisions which project to the neurohypophysis. A combined lesion and immunocytochemical approach has shown that the bulk of the afferent neuronal input from arcuate POMC cells enters the PVN from a ventral direction.     

Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat

Ascending projections from the medial pontine reticular formation, the mesencephalic reticular formation, and the median raphe nucleus were examined using the autoradiographic technique. The majority of the ascending fibers labeled after injections of [3H]-leucine into the nucleus pontis caudalis (RPC) course through the brainstem within the tracts of Forel (tractus fasciculorum tegmenti of Forel) and directly ventral to them. At the caudal diencephalon, Forel's bundle divides into dorsal and ventral components bound primarily for the dorsal thalamus and the subthalamus, respectively. RPC fibers project to several regions involved in oculomotor/visual functions. These include the abducens nucleus, the intermediate gray layer of the superior colliculus (SCi), the anterior pretectal nucleus (APN), the ventral lateral geniculate nucleus (LGNv), and regions of the central gray directly bordering the oculomotor nucleus, the interstitial nucleus of Cajal, and the nucleus of Darkschewitsch. Few, if any, fibers from RPC (or from nucleus pontis oralis-RPO) terminate within the oculomotor nucleus proper. Other sites receiving heavy projections from the RPC include adjacent regions of the pontomesencephalic reticular formation (RF), the parafascicular (PF) and central lateral (CL) nuclei of the thalamus and the fields of Forel/zona incerta (FF-ZI). RPO fibers also ascend predominantly in Forel's bundle. Other ascending tracts for these fibers are the medial longitudinal fasciculus and the central tegmental tract (CTT). RPO fibers distribute significantly to the same structures of the oculomotor/visual system receiving projections from RPC. The RPO projections to the SCi and the APN are particularly pronounced. RPO fibers terminate heavily in several nuclei located ventrally within the rostral midbrain/caudal diencephalon. These include major dopamine-containing cell groups (the retrorubral nucleus, the ventral tegmental area, and the substantia nigra-pars compacta) as well as the interpeduncular nucleus, the lateral mammillary nucleus, and the supramammillary nucleus. Other prominent targets for RPO fibers include the mesencephalic RF, specific regions of the central gray, the PF, the CL, the paracentral and central medial nuclei of the thalamus, and the FF/ZI. The major bundle of the ascending fibers labeled after injections of the mesencephalic reticular formation (MRF) travels within the CTT in a position just lateral to the central gray, but a significant number of labeled axons also course in Forel's bundle.(ABSTRACT TRUNCATED AT 400 WORDS)     

Efferent projections from the paraventricular nucleus mediating α2-noradrenergic feeding

Feeding behavior elicited by central injection of the α-noradrenergic agonists, norepinephrine (NE) and clonidine (CLON), are believed to be mediated via postsynapticα₂-type receptors located in the paraventricular nucleus (PVN). To map the course taken by essential efferent (descending) fibers of this PVN system for noradrenergically-stimulated feeding, the impact of diencephalic and lower brainstem coronal knife cuts, on the responses elicited by PVN-injected NE and CLON, was assessed. Rats that sustained damage in the periventricular gray area of the caudal thalamus and midbrain exhibited significant losses in feeding elicited by PVN injections of these drugs. In the case of animals with midbrain periventricular gray knife cuts, a significant increase in daily food intake was also observed, and this increase was positively correlated in magnitude with the attenuation of NE-induced feeding. This decrease in sensitivity toα₂-noradrenergic stimulation occurred with discrete periventricular knife cuts extending only 0.5 mm lateral to midline. In contrast, large ventral or lateral coronal knife cuts throughout the dorsal and ventral midbrain tegmentum left intact NE- and CLON-induced feeding. These findings provide evidence for localization of anatomical substrates which underlie PVNα₂-noradrenergic feeding. The efferent fibers of this system appear to exit from the PVN in a dorsomedial direction and course through the thalamic periventricular area. As this projection descends into the midbrain, it remains quite medial, maintaining this position throughout the midbrain central gray substance. At the level of the pons, just rostral to the locus coeruleus, this fiber projection appears to course ventrolaterally into the dorsolateral pontine tegmentum and possibly continue towards the dorsal vagal complex of the dorsomedial medulla.     

Afferent projections to affective attack sites in cat hypothalamus

Quiet biting attack by a cat on a rat was elicited by electrical stimulation of sites in the cat's lateral hypothalamus.Horseradish peroxidase was deposited at the attack sites. Cells containing reaction products were found in gyrus proreus, anterior and central medial amygdaloid nuclei, lateral and medial preoptic areas, substantia innominata, the bed nuclei of stria terminalis, and anterior commissure. The dorsomedial area of the hypothalamus, paraventricular nucleus, suprammamillary region, and posterior hypothalamic area also contained reactive cells. In the midbrain the ventral tegmental area of Tsai, the dorsal and superior central nuclei of the raphe, central gray matter and interpeduncular nucleus were regions with reactive cells. In the pontine region, the locus coeruleus, parabrachial nuclei, nucleus of the lateral lemniscus, and the dorsal tegmental nucleus of Gudden all had reactive cells.There are many structures which send afferent projections to quiet attack sites located in the hypothalamus and the pontine tegmentum. The commonality of afferents to attack sites lends credence to the notion that a complex, distributed, interactive network underlies the neural basis of attack behavior.     

Specificity in the efferent projections of the nucleus accumbens in the rat: Comparison of the rostral pole projection patterns with those of the core and shell

The efferent connections of the rostral pole of the rat accumbens, where distinct core and shell subterritories can not be identified, were examined with the aid of the anterogradely transported plant lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L), for comparison with the previously reported projection patterns of the accumbal core and shell. Injection sites and transported PHA-L were evaluated with the aid of reference to adjacent sections processed to display substance P or calbindin 28 kD immunoreactivities, i.e., markers that demonstrate the core and shell. Lateral parts of the rostral pole gave rise to a “core-like” projection system that involved the rostroventral globus pallidus, subcommissural ventral pallidum, entopeduncular nucleus and an adjacent part of the lateral hypothalamus, lateral ventral tegmental area, dorsal pars compacta, and structures in the lateral mesencephalic tegmentum and central grey. The medial part of the rostral pole gave rise to a “shell-like” innervation of the subcommissural ventral pallidum, lateral preoptic region, lateral hypothalamus, ventral tegmental area, dorsalmost pars compacta, retrorubral field, lateral midbrain tegmentum, and central grey. In contrast to the large numbers of axon varicosities observed through the entire length of lateral hypothalamus following shell injections, dense accumulations of axon collaterals and varicosities in hypothalamus were limited to the levels of origin of the stria medullaris bundle and entopeduncular nucleus and to the posterlateral region following medial injections. The medial part of the rostral pole contributed some projections to preoptic and sublenticular regions, but not to the bed nucleus of the stria terminalis. Noteworthy concentrations of calbindin immunoreactive cells observed in the lateral rostral pole correlate with the origin of the “basal ganglia-like” projection system, provoking the speculation that ventral striatal calbindin immunoreactive cells contribute principally to basal ganglia-like projections while cells lacking calbindin immunoreactivity contribute to the innervation of hypothalamus and midbrain tegmentum. © 1993 Wiley-Liss, Inc.     

Mamillary body in the rat: topography and synaptology of projections from the subicular complex, prefrontal cortex, and midbrain tegmentum

The retrograde and anterograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) has been used to trace afferent connections of the rat mamillary body (MB) at the light and electron microscopic levels. Injections of WGA-HRP into different parts of the MB resulted in heavy retrograde labeling in the subicular complex, medial prefrontal cortex, and dorsal and ventral tegmental nuclei. Injections of WGA-HRP into each of these brain regions, respectively, resulted in anterograde labeling with specific distributions and characteristic synaptic organizations in the MB. Projections from the rostrodorsal and caudoventral subiculum terminated in a topographically organized laminar fashion in the medial mamillary nucleus bilaterally, whereas afferent projections from the presubiculum and parasubiculum terminated only in the lateral mamillary nucleus. Labeled axon terminals which originated from the subicular complex were characterized by round vesicles and formed asymmetric synaptic junctions with small-diameter dendrites and dendritic spines in the medial and lateral mamillary nuclei. Projections from the prefrontal cortex originated mainly in the infralimbic area and to a lesser degree in the prelimbic and anterior cingulate areas. Injections of tracer into these brain regions gave rise to dense labeling of axon terminals in the medial mamillary nucleus, pars medianus, and in the anterior dorsomedial portion of the pars medialis. The labeled terminals were characterized by round vesicles and formed asymmetric synaptic junctions with small-diameter dendrites and dendritic spines. Projections from the dorsal tegmental nucleus terminated in the ipsilateral lateral mamillary nucleus, whereas afferent projections from the anterior and posterior subnuclei of the ventral tegmental nucleus terminated topographically in the medial mamillary nucleus. The ventral tegmental nucleus, pars anterior projected to the midline region of the medial nucleus and the dorsolateral and ventromedial subdivisions of the pars posterior projected to medial and lateral parts of the medial nucleus, respectively. In contrast to the synaptic morphology of subicular complex and medial prefrontal cortex axon terminals in the MB, labeled axon terminals in the MB which originated from the midbrain tegmentum were characterized by pleomorphic vesicles and formed symmetric synaptic junctions with neuronal somata and proximal dendrites as well as distal dendrites and dendritic spines.(ABSTRACT TRUNCATED AT 400 WORDS)     

Evidence for GABAergic projections from the tegmental nuclei of Gudden to the mammillary body in the rat

Immunochemical studies have demonstrated the presence of large numbers of cells immunoreactive for glutamic acid decarboxylase (GAD) within the dorsal and ventral tegmental nuclei of gudden. Following injections of Fluoro-Gold into the medial mammillary nucleus, a substantial proportion of the retrogradely labeled neurons within the ventral tegmental nucleus displayed GAD-like immunoreactivity. Conversely, electrolytic or excitotoxic lesions of the ventral tegmental nucleus produced a large decrease in the number of fibers and terminals immunoreactive for GAD within the medial mammillary nucleus. In contrast, electrolytic lesions of the dorsal tegmental nucleus were found to produced a large decrease in GAD-like immunoreactivity which was restricted to the lateral mammillary nucleus. Control lesions placed caudal to the dorsal tegmental nucleus were without effect. These findings suggest that the dorsal and ventral nuclei send a substantial, topographically organized, GABAergic input to the mammillary body.     

Fiber degeneration associated with hyperphagia-inducing knife cuts in the hypothalamus

The pattern of axonal degeneration associated with hyperphagia-producing hypothalamic knife transections was investigated using the Fink-Heimer method for staining of degenerating axons and their terminal endings. Histological analysis of silver-stained material after parasagittal knife cuts which result in hyperphagia and obesity revealed fiber degeneration coursing longitudinally in the medial forebrain bundle including the perifornical component to reach the nucleus accumbens, the diagonal band, the preoptic-anterior hypothalamic junction, the lateral hypothalamus, the zona incerta, the periventricular thalamus, the parafascicular thalamic nucleus, the substantia nigra pars compacta, the central gray matter, the ventral tegmental area of T'sai and the superior colliculus. The data obtained in the present study lend support to the suggestion that projections coursing in the medial forebrain bundle interconnect the anteriomedial hypothalamus and the midbrain tegmentum and may underlie the hyperphagia and obesity produced by hypothalamic knife cuts.