Distribution of vasopressin and vasoactive intestinal polypeptide (VIP) fibers in the human hypothalamus with special emphasis on suprachiasmatic nucleus efferent projections

The human suprachiasmatic nucleus (SCN) is located in the basal part of the anterior hypothalamus and is considered as the biological clock that generates circadian rhythms and synchronizes the daily activity pattern with the environmental light-dark cycle. However, the mechanisms and pathways by which the SCN transmits its information to the other brain areas are unknown. Therefore, in the present study, we investigated the efferent projections of the SCN by the immunocytochemical staining of two major peptidergic SCN neurotransmitters: vasopressin (VP) and vasoactive intestinal polypeptide (VIP). It confirmed that these peptides are present in different subdivisions of the SCN. The results of this investigation show that VP and VIP fibers arising from the SCN were detected to branch extensively and hence seem to innervate the SCN itself and the central and medial part of the anteroventral hypothalamic area (AVH), the area below the paraventricular nucleus (sub-PVN), the ventral part of the paraventricular nucleus (PVN), and the dorsomedial nucleus of the hypothalamus (DMH). There appeared to be substantial congruity between the presumptive human SCN projections and those as observed by tracing in rat or hamster. Regarding the anatomical organization of the human SCN projections, the main projection areas appeared to be the AVH, the sub-PVN, the ventral part of the PVN, and the DMH. The observation that VIP and in particular VP fibers pass between the SCN and the PVN suggests that the human SCN and the PVN may have a direct anatomical connection. In addition, VP and VIP fibers were detected in several other hypothalamic areas that are not known to have clear direct connections to the SCN. The possible origin of these VP and VIP fibers is discussed. J. Comp. Neurol. 383:397-414, 1997. © 1997 Wiley-Liss, Inc.     

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)     

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

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

Decussations of the descending paraventricular pathways to the brainstem and spinal cord autonomic centers.

Decussations of descending fibers of the hypothalamic paraventricular nucleus (PVN) were investigated by using Phaseolus vulgaris-leucoagglutinin (PHA-L) in intact and brainstem-operated rats. Fibers descend ipsilaterally along the brainstem and spinal cord and decussate at four levels: 1) Supramamillary decussations (SM). PVN fibers reach this area through the lateral hypothalamus and along the third ventricle in the dorsal hypothalamus. In the posterior hypothalamus some fibers crossover in the SM and terminate in the supramamillary region bilaterally. 2) Pontine tegmentum. PVN fibers run in the lateral part of the tegmentum arching to the basis of the pons. Some fibers crossover under the fourth ventricle. The locus ceruleus and the Barrington's nucleus receive bilateral innervation with ipsilateral dominance. 3) Commissural part of the nucleus of the solitary tract (NTS). The major crossover of PVN fibers is found here. The decussated fibers form a dense network here, and loop rostralward to innervate the entire NTS. A midsagittal knife-cut through the NTS eliminated paraventricular-fibers on the contralateral side. Synaptic contacts between PHA-L-labeled boutons and tyrozine hydroxilase-positive neurons were verified in the NTS. The caudal ventrolateral medulla also receives bilateral innervation. 4) Lamina X of the thoracic spinal cord. Paraventricular fibers enter the lateral funiculus ipsilaterally and innervate the intermediolateral cell column (IML). Some fibers cross the midline ventral and dorsal to the central canal running to the contralateral IML, at the level of the decussation. Our results demonstrated that paraventricular projections form a continuous descending pathway on their side of origin, and provide crossover fibers which may terminate segmentally without forming long tracts after crossover.     

Connections of the posterior nucleus of the amygdala.

The connections of a relatively homogeneous band of neurons in the caudal amygdala have been examined with anterograde and retrograde axonal tracing methods in the rat. This region, called here the posterior nucleus of the amygdala (PA), corresponds in part to an area that has been referred to as the cortico-amygdaloid transition area, posterior part of the medial nucleus of the amygdala, amygdalo-hippocampal transition area, and posteromedial basal nucleus. Experiments with fluorogold and phaseolus vulgaris leucoagglutinin (PHAL) indicate that the major neuronal input to the PA arises in the ventral premammillary nucleus, and that substantial projections also arise in olfactory-related areas such as the medial nucleus of the amygdala, bed nucleus of the accessory olfactory tract, and posterior cortical nucleus of the amygdala, as well as in the ventral subiculum and adjacent parts of hippocampal field CA1. Other seemingly minor inputs, including cholinergic fibers from the substantia innominata, dopaminergic fibers from the ventral tegmental area, and serotoninergic fibers from the dorsal nucleus of the raphe, were also identified. The efferent projections of the PA as determined with the PHAL method appear to follow five major routes: 1) a relatively small group of laterally directed fibers innervates the dorsal endopiriform nucleus, and a few of these fibers reach cortical area TR and the lateral entorhinal area; 2) another small group of fibers courses medially to innervate the ventral subiculum and adjacent parts of field CA1; 3) many fibers course ventrally to innervate the outer molecular layer of the medial part of the posterior cortical nucleus of the amygdala; 4) a moderate group of fibers courses rostrally to innervate primarily the posterodorsal part of the medial nucleus of the amygdala, although some fibers continue on to end less densely in rostral parts of the medial nucleus of the amygdala before leaving the amygdala through the ansa peduncularis; and 5) the major output of the PA courses through the stria terminalis. One branch of this pathway massively innervates the principal nucleus of the bed nuclei of the stria terminalis before entering the medial hypothalamus, where it ends massively in the anteroventral periventricular and medial preoptic nuclei, ventrolateral part of the ventromedial nucleus and adjacent parts of the basal lateral hypothalamic area, and ventral premammillary nucleus. The other branch sends fibers to the ventral lateral septal nucleus, nucleus accumbens, olfactory tubercle, and infralimbic area of the prefrontal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)     

Efferents from the medial anterior hypothalamic area in the guinea pig

Medial anterior hypothalamic connections were studied with H³-proline and autoradiography. Most of the axons projected to other hypothalamic nuclei. The major pathways were found ventral medial to the fornix and in the periventricular tract. Substantial projections were apparent in the ventromedial and dorsomedial nuclei with less label in the arcuate nucleus. The dorsal premammillary nuclei were labeled bilaterally, particularly with more caudal injections of anterior hypothalamus. Efferents were evident in the posterior hypothalamus and continued into the central gray of the midbrain. Labeled fibers reached the ventral tegmental area and in the reticular formation were traced only through pons. Rostral projections were to the medial and lateral preoptic areas and ventral lateral septum. The bed nucleus of stria terminalis was labeled and a very few fibers reached the medial amygdaloid nucleus. The periventricular nucleus of thalamus was labeled.     

Afferent connections to the amygdaloid complex of the rat and cat: II. Afferents from the hypothalamus and the basal telencephalon

The projections from the basal telencephalon and hypothalamus to each nucleus of the amygdaloid complex of the rat, and to the central amygdala of the cat, were investigated by the use of retrograde transport of horseradish peroxidase (HRP). The enzyme was injected stereotaxically by microiontophoresis, using three different approaches. The ventral pallidum (Heimer, '78) and ventral part of the globus pallidus were found to project to the lateral and basolateral nuclei of the amygdala. The substantia innominata projects diffusely to the entire amygdaloid complex, except to the lateral nucleus and the caudal part of the medial nucleus. The anterior amygdaloid area shows a similar projection field, the only difference being that this structure does not project to any parts of the medial nucleus. The dorsal subdivision of the nucleus of the lateral olfactory tract sends fibers to the ipsilateral as well as the contralateral basolateral nucleus, and possibly to the ipsilateral basomedial and cortical amygdala. The ventral subdivision of the nucleus of the lateral olfactory tract was massively labeled after an injection in the ipsilateral central nucleus, but this injection affected the commissural component of the stria terminalis. The nucleus of the horizontal limb of the diagonal band of Broca connects with the medial, central, and anterior cortical nuclei, whereas the bed nucleus of stria terminalis and medial preoptic area are related to the medial nucleus predominantly. The lateral preoptic area is only weakly labeled after intra-amygdaloid HRP injections. The hypothalamo-amygdaloid projections terminate preponderantly in the medial part of the amygdaloid complex. Thus, axons from neurons in the area dorsal and medial to the paraventricular nucleus of the hypothalamus distribute to the medial nucleus and intra-amygdaloid part of the bed nucleus of stria terminalis. Most of the amygdalopetal fibers from the ventromedial, ventral premammillary, and arcuate nuclei of the hypothalamus end in the medial nucleus, but some extend into the central nucleus. A few fibers from the ventromedial nucleus of the hypothalamus reach the basolateral nucleus. The lateral hypothalamic area projects heavily to the central nucleus, and more sparsely to the medial and basolateral nuclei. The dorsal hypothalamic area and supramammillary nucleus show restricted projections to the central and basolateral nuclei, respectively. There are only a modest number of crossed hypothalamo-amygdaloid fibers. Most of these originate in the ventromedial nucleus of the hypothalamus and terminate in the contralateral medial nucleus. The projections from the basal telencephalon and hypothalamus to the central nucleus of the amygdala of the cat are similar to the corresponding projections in the rat.     

Ascending projections of the mammillary region in the pigeon: emphasis on telencephalic connections

The ascending projections of the mammillary region of the hypothalamus and adjacent posterolateral hypothalamus were investigated by autoradiographic and horseradish peroxidase histochemical techniques. Analysis of the anterograde data revealed that the main contingent of mammillary fibers ascends in the medial forebrain bundle (MFB) in the lateral hypothalamic area. These fibers distribute to a number of telencephalic regions via three pathways. (1) Fibers course dorsomedially into the medial and lateral parts of the septum and continue into the hippocampus with a dense terminal field in the parahippocampal area. (2) Laterally coursing fibers project to area corticoidea dorsolateralis, area temporo-parieto-occipitalis, cortex piriformis, and the posterior part of archistriatum. (3) The fibers remaining in the MFB ascend into the "ventral paleostriatum," olfactory tubercle, and into the lateral and ventral borders of the rostral portion of lobus parolfactorius (LPO). Numerous fibers leave the LPO region and course dorsally into the deep layer of the Wulst, hyperstriatum dorsale (HD). Many fibers continue dorsolaterally through the HD and enter an unnamed region of the dorsolateral telencephalon (lateral to the vallecula) at the level of the olfactory bulb. Retrograde transport experiments revealed that the perikarya of origin-of-fiber projections to the parahippocampal area and to the rostral, dorsolateral telencephalon reside not only in nucleus mammillaris lateralis but also in posterolateral hypothalamic cells rostral and dorsal to this nucleus. The projection of these hypothalamic cells to the hippocampal formation and many other telencephalic regions in birds suggests that these cells are similar to the mammalian supramammillary nucleus and posterolateral hypothalamus rather than the mammillary nuclei.     

The efferent connections of the anterior hypothalamic area of the rat, cat and monkey.

The general morphology and topographic relations of the anterior hypothalamic area (AHA) in the rat, cat and squirrel monkey have been described, and its efferent connections analyzed autoradiographically, after small injections of 3H-labeled amino acids into, or around, the area. In all three species the AHA is rather poorly separated from the surrounding preoptic and hypothalamic areas and nuclei but shows three distinct cellular condensations, located rostrally, centrally, and posterodorsally. Closely associated with the AHA are the retrochiasmatic area, the anterior periventricular nucleus and the scattered neurons usually referred to as the accessory supraoptic nucleus. The AHA has primarily short connections to the adjoining medial preoptic area, the lateral hypothalamic area, the periventricular nucleus, the dorsomedial nucleus, and to the "capsule" of the ventromedial nucleus. However, it also has certain more distant projections, rostrally to a narrow zone centered in the ventral part of the lateral septal nucleus, and caudally to the dorsal premammillary nuclei, the posterior hypothalamic area and the central gray. There is some evidence to suggest that the various subdivisions of the AHA have different efferent connections. Thus the posterodorsal cell condensation appears to give rise to the bilateral projection to the dorsal premammillary nuclei, while the projections to the septum, the posterior hypothalamic area and the central gray seem to have their origin in the central condensation. Similarly, the retrochiasmatic area sends its efferents through the ventral supraoptic commissure to the amygdala, the anterior periventricular nucleus contributes to the periventricular fiber system and to the external lamina of the median eminence, and the accessory supraoptic neurons project to the internal lamina of the median eminence.     

Efferent connections of the substantia innominata in the rat

The efferent connections of the substantia innominata (SI) were investigated employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The projections of the SI largely reciprocate the afferent connections described by Grove (J. Comp. Neurol. 277:315-346, '88) and thus further distinguish a dorsal and a ventral division in the SI. Efferents from both the dorsal and ventral divisions of the SI descend as far caudal as the ventral tegmental area, substantia nigra, and peripeduncular area, but projections to pontine and medullary structures appear to originate mainly from the dorsal SI. Within the amygdala and hypothalamus, which receive widespread innervation from the SI, the dorsal SI projects preferentially to the lateral part of the bed nucleus of the stria terminalis; the lateral, basolateral, and central nuclei of the amygdala; the lateral preoptic area; paraventricular nucleus of the hypothalamus; and certain parts of the lateral hypothalamus, prominently including the perifornical and caudolateral zones described previously. The ventral SI projects more heavily to the medial part of the bed nucleus of the stria terminalis; the anterior amygdaloid area; a ventromedial amygdaloid region that includes but is not limited to the medial nucleus; the lateral and medial preoptic areas; and the anterior hypothalamus. Modest projections reach the lateral hypothalamus, with at least a slight preference for the medial part of the region, and the ventromedial and arcuate hypothalamic nuclei. Both SI divisions appear to innervate the dorsomedial and posterior hypothalamus and the supramammillary region. In the thalamus, the subparafascicular, gustatory, and midline nuclei receive a light innervation from the SI, which projects more densely to the medial part of the mediodorsal nucleus and the reticular nucleus. Cortical efferents from at least the midrostrocaudal part of the SI are distributed primarily in piriform, infralimbic, prelimbic, anterior cingulate, granular and agranular insular, perirhinal, and entorhinal cortices as well as in the main and accessory olfactory bulbs. The cells of origin for many projections arising from the SI were identified as cholinergic or noncholinergic by combining the retrograde transport of WGA-HRP with histochemical and immunohistochemical procedures to demonstrate acetylcholinesterase activity or choline acetyltransferase immunoreactivity. Most of the descending efferents of the SI appear to arise primarily or exclusively from noncholinergic cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Efferent projections of the suprachiasmatic nucleus in the golden hamster (Mesocricetus auratus)

The efferent projections of the suprachiasmatic nucleus (SCN) in the golden hamster have been examined by using the anterograde tracer Phaseolus vulgaris leucoagglutinin (Pha-L). SCN projections were further localized through a combination of restricted SCN-lesions and immunocytochemistry for three well-known peptidergic transmitters contained in SCN neurons, viz. vasopressin (VP), vasoactive intestinal peptide (VIP), and gastrin-releasing peptide (GRP). Thus, major terminal fields of SCN-derived VP were detected in the medial preoptic nucleus, the anterior part of the paraventricular nucleus of the thalamus (PVA), the medial parvicellular part of the paraventricular nucleus of the hypothalamus (PVN), and the medial part of the dorsomedial nucleus of the hypothalamus (DMH). VIP-containing projections from the SCN were discovered in the PVA, anterior and dorsal parvicellular divisions of the PVN, subparaventricular area, and medial DMH. Efferent fibers from the SCN containing GRP were restricted to the subparaventricular area, medial DMH, and supraoptic nucleus. In addition, Pha-L tracing indicated the existence of SCN projections which could not be ascribed to one of the presently investigated peptides. Furthermore, a pronounced innervation of the contralateral SCN was observed, of which the neurotransmitter remains to be established. The results of the present study indicate that the different neuronal populations in the SCN, as characterized by their transmitter content, also show a clear diversity in their preferential target areas. © 1993 Wiley-Liss, Inc.     

Activation of neurons in the hypothalamic dorsomedial nucleus via hypothalamic projections of the nucleus of the solitary tract following refeeding of fasted rats

We report that satiation evokes neuronal activity in the ventral subdivision of the hypothalamic dorsomedial nucleus (DMH) as indicated by increased c‐fos expression in response to refeeding in fasted rats. The absence of significant Fos activation following food presentation without consumption suggests that satiation but not craving for food elicits the activation of ventral DMH neurons. The distribution pattern of the prolactin‐releasing peptide (PrRP)‐immunoreactive (ir) network showed remarkable correlations with the distribution of activated neurons within the DMH. The PrRP‐ir fibers and terminals were immunolabeled with tyrosine hydroxylase, suggesting their origin in lower brainstem instead of local, hypothalamic PrRP cells. PrRP‐ir fibers arising from neurons of the nucleus of the solitary tract could be followed to the hypothalamus. Unilateral transections of these fibers at pontine and caudal hypothalamic levels resulted in a disappearance of the dense PrRP‐ir network in the ventral DMH while PrRP immunoreactivity was increased in transected fibers caudal to the knife cuts as well as in perikarya of the nucleus of the solitary tract ipsilateral to the transections. In accord with these changes, the number of Fos‐expressing neurons following refeeding declined in the ipsilateral but remained high in the contralateral DMH. However, the Fos response in the ventral DMH was not attenuated following chemical lesion (neonatal monosodium glutamate treatment) of the hypothalamic arcuate nucleus, another possible source of DMH inputs. These findings suggest that PrRP projections from the nucleus of the solitary tract contribute to the activation of ventral DMH neurons during refeeding, possibly by transferring information on cholecystokinin‐mediated satiation.     

Human retinohypothalamic tract as revealed by in vitro postmortem tracing

Animal experimental studies have shown that the retinohypothalamic tract (RHT) is an anatomical and functionally distinct retinofugal pathway mediating photic entrainment of circadian rhythms. In the present study, RHT projections were studied in the human brain by our recently developed postmortem tracing technique with neurobiotin as a tracer. Similar patterns of labeling were observed in brains of one control subject without nuerological or mental disorders and five patients with Alzheimer's disease. The topography of RHT projections has several characteristics. (1) RHT fibers leave the optic chiasm and enter the hypothalamus medially and laterally at the anterior level of the suprachiasmatic nucleus (SCN). (2) The medial fibers enter the ventral part of the SCN and innervate the ventral SCN over its entire length, but the density decreases gradually from anterior to posterior. Labeled RHT fibers in the SCN make contact mainly with immunocytochemically positive neurotensin or vasoactive intestinal polypeptide neurons and only occasionally with vasopressin-positive neurons located in the ventral part of the SCN. (3) Only few projections to the dorsal part of the SCN and the anteroventral part of the hypothalamus were found. (4) Lateral projections reach the ventral part of the ventromedial SON and the area lateral to the SCN. No projections were observed to other hypothalamic areas. The presence of an RHT in humans suggests that the RHT may serve a function in humans similar to that demonstrated in animals. J. Comp. Neurol. 397:357–370, 1998. © 1998 Wiley-Liss, Inc.     

Subicular efferents to histaminergic neurons in the posterior hypothalamic region of the rat studied with PHA-L tracing combined with histidine decarboxylase immunocytochemistry.

The projections from the subiculum to histaminergic cells in the posterior hypothalamic region of the rat were studied by means of anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L) combined with histidine decarboxylase (HDC)-immunohistochemistry. PHA-L was injected at various loci along the dorsoventral and proximodistal axes of the subiculum. This resulted in labeling of the fornix and of terminal plexuses at various locations in the diencephalon and the mammillary body. Following deposition of PHA-L in the proximal part of the dorsal subiculum, labeled fibers in the posterior hypothalamus were confined to the mammillary nuclei, whereas after injections of PHA-L in the distal part of the dorsal subiculum and the entire ventral subiculum, labeled fibers were also present in clusters of histaminergic cells located around the mammillary nuclei. The density of the PHA-L labeled fibers within these clusters increased from low to moderate in association with a shift of the injection sites from dorsal to ventral and from proximal to distal parts of the subiculum, i.e., the highest fiber labeling was seen after injections of PHA-L in the distal part of the ventral subiculum. In the latter experiments, PHA-L labeled fibers reached HDC-immunoreactive neurons in the tuberal magnocellular nucleus, the deepest layer of the caudal magnocellular nucleus, the two bridges of histaminergic cells in the posterior hypothalamus, and the histaminergic neurons scattered in the supramammillary region. A few labeled fibers invaded the postmammillary caudal magnocellular nucleus. The presence of varicosities on the PHA-L labeled fibers in close proximity to the cell bodies and dendrites of the histaminergic neurons suggest the existence of synaptic contacts.     

Neural associations of the substantia innominata in the rat: afferent connections

The afferent connections of the substantia innominata (SI) in the rat were determined employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), in combination with histochemical procedures to characterize the neuropil of the SI and identify cholinergic cells. Both neurochemical and connectional data establish that the SI is organized into a dorsal and a ventral division. Each of these divisions is strongly affiliated with a different region of the amygdala, and, together with its amygdalar affiliate, forms part of one of two largely distinct constellations of interconnected forebrain and brainstem cell groups. The dorsal SI receives selective innervation from the lateral part of the bed nucleus of the stria terminalis, the central and basolateral nuclei of the amygdala, the fundus of the striatum, distinctive perifornical and caudolateral zones of the lateral hypothalamus, and caudal brainstem structures including the dorsal raphe nucleus, parabrachial nucleus, and nucleus of the solitary tract. Projections preferentially directed to the ventral SI arise from the medial part of the bed nucleus of the stria terminalis, the rostral two-thirds of the medial nucleus of the amygdala, a large region of the rat amygdala that lies ventral to the central nucleus, the medial preoptic area, anterior hypothalamus, medialmost lateral hypothalamus, and the ventromedial hypothalamus. Both SI divisions appear to receive afferents from the dorsomedial and posterior hypothalamus, supramammillary region, ventral tegmental area, and the peripeduncular area of the midbrain. Projections to the SI whose selectivity was not determined originate from medial prefrontal, insular, perirhinal, and entorhinal cortex and from midline thalamic nuclei. Findings from both PHA-L and WGA-HRP experiments additionally indicate that cell groups preferentially innervating a single SI division maintain numerous projections to one another, thus forming a tightly linked assembly of structures. In the rat, cholinergic neurons that are scattered throughout the SI and in parts of the globus pallidus make up a cell population equivalent to the primate basal nucleus of Meynert (Mesulam et al.: Neuroscience 10:1185-1201, '83). PHA-L-filled axons, labelled from lectin deposits in the dorsal raphe nucleus, peripeduncular area, ventral tegmental area, or caudomedial hypothalamus were occasionally seen to approach individual cholinergic neurons int he SI, and to contact the surface of such cells with axonal varicosities (putative synaptic boutons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunohistochemical mapping of neuropeptides in the premamillary region of the hypothalamus in rats

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in the premamillary region of the rat hypothalamus using light microscopic immunohistochemistry. Alternate coronal sections through the posterior third of the hypothalamus of normal and colchicine-treated male rats were immunostained for 19 different neuropeptides and their distributions were mapped throughout the following structures: the ventral and dorsal premamillary, the supramamillary, the tuberomamillary and the posterior hypothalamic nuclei, as well as the premamillary portion of the arcuate nucleus and the postinfundibular median eminence. Seventeen of the investigated neuropeptides were present in neuronal perikarya, nerve fibers and terminals while the gonadotropin associated peptide and vasopressin occurred only in fibers andn terminals. Growth hormone-releasing hormone-, somatostatin-, α-melanocyte stimulating hormone-, adrenocorticotropin, β-endorphin- and neuropeptide Y-immunoreactive neurons were seen exclusively in the premamillary portion of the arcuate nucleus. Thyrotropin-releasing hormone-, dynorphin A- and galanin-containing neurons were distributed mainly in the arcuate and the tuberomamillary nuclei. A high number of methionine- and leucine-enkephalin-immunoreactive cells were detected in the arcuate and dorsal premamillary nuclei, as well as in the area ventrolateral to the fornix. Substance P-immunoreactive perikarya were present in very high number within the entire region, in particular in the ventral and dorsal premamillary nuclei. Cell bodies labelled with cholecystokinin- and calcitonin gene-related peptide antisera were found predominantly in the supramamillary and the terete nuclei, respectively. Corticotropin-releasing hormone-, vasoactive intestinal polypeptide- and neurotensin-immunoreactive neurons were scattered randomly in low number, mostly in the arcuate and the ventral and dorsal premamillary nuclei. Peptidergic fibers were distributed unevenly throughout the whole region, with each peptide showing an individual distribution pattern. The highest density of immunoreactive fibers was presented in the ventral half of the region including the arcuate, the ventral premamillary and the tuberomamillary nuclei. The supramamillary nucleus showed moderately dense fiber networks, while the dorsal premamillary and the posterior hypothalamic nuclei were poor in peptidergic fibers.     

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.     

Phaseolus vulgaris leuco-agglutinin tracing of intrahypothalamic connections of the lateral, ventromedial, dorsomedial and paraventricular hypothalamic nuclei in the rat

Intrahypothalamic connections of the lateral (LHA), ventromedial (VMH), dorsomedial (DMH) and paraventricular (PVN) hypothalamic nuclei were studied with anterograde transport of iontophoretically injected Phaseolus vulgaris leuco-agglutinin and the immunocytochemical detection of labeled structures. The LHA was found to give rise to a minor projection in the VMH, whereas the VMH in reverse maintains few connections with the ventromedial part of the tuberal LHA. Tracer deposits in both the LHA and VMH resulted in anterograde terminal labeling in the DMH. The DMH, in turn, donates a small number of projections to the LHA and VMH. The main projection of the DMH is aimed at the parvocellular paraventricular nucleus. Direct outflow pathways from the VMH to the PVN were not found, but lectin injections in the LHA on the other hand gave rise to terminal labeling in both the parvocellular and magnocellular divisions of the PVN. The PVN in turn was found to give only minor reciprocal projections to the LHA, DMH and VMH. These findings indicate that the main stream of connections in the hypothalamus runs from the LHA and VMH to the DMH, and from the DMH to the PVN. The identified circuitry patterns were discussed with respect to the role of the hypothalamus in the control of homeostasis and metabolic regulation, and more specifically in relation to the modulation of the hormone release from the pancreas and adrenal glands.