Structural characterization of a hypothalamic visceromotor pattern generator network

A high resolution PHAL analysis of axonal connections suggests the existence of a visceromotor pattern generator network in the periventricular region of the rat hypothalamus (HVPG), and a preliminary account of its structure is provided here. Six nodes identified thus far include the dorsomedial nucleus and five small nuclei in the preoptic region (anteroventral and anterodorsal preoptic, parastrial, median preoptic, and anteroventral periventricular). Aside from its location between the neuroendocrine motor zone and the medial hypothalamic nuclei (behavior control column), three other primary features characterize the HVPG network. First, each HVPG nucleus generates a pattern of terminal fields that differentially targets a unique set of hypothalamic neuroendocrine motoneuron pools, and of preautonomic parts of the paraventricular nucleus. Second, the six HVPG nuclei are massively interconnected themselves. And third, the majority of projections from the HVPG nuclei remain within the medial half of the hypothalamus; additional outputs reach the septum, other parts of the diencephalon, and the brainstem central gray. Possible control of activity in the HVPG by neural inputs from the cerebral hemispheres, sensory systems, behavioral state-related cell groups, and the hypothalamic behavior or motivation control column is discussed, along with certain key functional data related to HVPG nuclei. Finally, the HVPG is incorporated into a working model of hypothalamic organization.     

Comparative study of the sources of neuronal projections to the site of gonadotrophin-releasing hormone perikarya and to the anteroventral periventricular nucleus in female rats

The rat ovulatory cycle is dependent on the preoptic region encompassing the gonadotrophin-releasing hormone (GnRH) perikarya and the anteroventral periventricular nucleus (AVPV). Retrograde tract tracing was used to identify and compare the sources of inputs to these sites in female rats. Within the telencephalon and diencephalon, the incidence of retrograde labelling from both sites was moderate to abundant in the ventral lateral septum, posteromedial bed nucleus of the stria terminalis, amygdalohippocampal area and the periventricular, medial preoptic, anterodorsal preoptic, dorsomedial suprachiasmatic, arcuate, and posterior ventrolateral ventromedial hypothalamic nuclei. In these regions, the incidence of retrograde labelling was either greater from the AVPV than from the GnRH perikarya site or similar from both sites. In the medial amygdaloid, parastrial, striohypothalamic, and ventral premammillary nuclei, the retrograde labelling from the AVPV greatly exceeded the sparse incidence from the GnRH perikarya site. In contrast, retrograde labelling from the GnRH perikarya site predominated in the median preoptic, lateroanterior and dorsomedial hypothalamic nuclei, subparaventricular zone, and retrochiasmatic area; it was abundant in the AVPV. Caudal to the diencephalon, retrograde labelling from either site was sparse, except in the lateral parabrachial nucleus, which displayed a particularly high incidence from the GnRH perikarya site. Other mesencephalic regions labelled from either site included the periaqueductal gray and dorsal and median raphe nuclei. The most caudal labelling was found in the ventrolateral medulla and region of the solitary tract nucleus; this was almost exclusively from the GnRH perikarya site. These findings further elucidate the neuroanatomical connections underlying the control of the ovulatory cycle.     

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.     

Projections of the sexually dimorphic anteroventral periventricular nucleus in the female rat

The anteroventral periventricular nucleus of the hypothalamus (AVPV) is a sexually dimorphic nucleus in the preoptic region that appears to be a nodal point in forebrain circuits, mediating hormonal feedback on gonadotropin secretion. The results of anterograde transport experiments indicate that the AVPV sends ascending projections to the ventral part of the lateral septal nucleus, the parastrial nucleus, and the region adjacent to the vascular organ of the lamina terminalis (OVLT) that contains a subpopulation of gonadotropin releasing hormone (GnRH)-containing neurons. The majority of projections from the AVPV pass caudally through the periventricular zone of the hypothalamus and form dense terminal fields in the periventricular nuclei, parvicellular parts of the paraventricular nucleus, and in the arcuate nucleus. Inputs to medial zone nuclei are more limited, with substantial projections to only the medial preoptic and dorsomedial nuclei. The AVPV sends few projections to the caudal brainstem, but terminals were observed reliably in the periaqueductal gray and medial part of the nucleus of the solitary tract. Anterograde double-labeling experiments demonstrate terminals derived from neurons in the AVPV in close apposition to GnRH-containing neurons in the preoptic region, and to dopaminergic neurons in the arcuate nucleus. Thus, the organization of projections from the AVPV in female rats suggests that neurons in this nucleus may influence the secretion of luteinizing hormone and prolactin through direct projections to GnRH neurons and tuberoinfundibular dopaminergic neurons. J. Comp. Neurol. 384:142-164, 1997. © 1997 Wiley-Liss, Inc.     

Organization of projections from the ventromedial nucleus of the hypothalamus: A Phaseolus vulgaris-Leucoagglutinin study in the rat

The organization of projections from the four parts of the ventromedial nucleus (VMH) and a ventrolaterally adjacent region tentatively identified as the tuberal nucleus (TU) have been analyzed with small injections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Extrinsic and intranuclear projections of each part of the VMH display clear quantitative differences, whereas the overall patterns of outputs are qualitatively similar. Overall, the VMH establishes massive intrahypothalamic terminal fields in other parts of the medial zone, tending to avoid the periventricular and lateral zones. The ventrolateral VMH is more closely related to other parts of the hypothalamus that also express gonadal steroid hormone receptors, including the medial preoptic, tuberal, and ventral premamillary nuclei, whereas other parts of the VMH are more closely related to the anterior hypothalamic and dorsal premammillary nuclei. All parts of the VMH project to the zona incerta (including the A13 region) and parts of the midline thalamus, including the paraventricular and parataenial nuclei and nucleus reuniens. The densest inputs to the septum are to the bed nuclei of the stria terminalis, where the ventrolateral and central VMH innervate the anteroventral and anterodorsal areas and transverse and interfascicular nuclei, whereas the anterior and dorsomedial VMH innervate the latter two. The central, lateral, and medial amygdalar nuclei receive substantial inputs from various parts of the VMH. Other regions of the telencephalon, including the nucleus accurmbens and the piriform-amygdaloid, infralimbic, prelimbic, anterior cingulate, agranular insular, piriform, perirhinal, entorhinal, and postpiriform transition areas, also receive sparse inputs. All parts of the VMH send a massive, topographically organized projection to the periaqueductal gray. Other brainstem terminal fields include the superior colliculus, peripeduncular area, locus coeruleus, Barrington's nucleus, parabrachial nucleus, nucleus of the solitary tract, and the mesencephalic, pontine, gigantocellular, paragigantocellular, and parvicellular reticular nuclei. The projections of the TU are similar to, and a subset of, those from the VMH and are thus not nearly as widespread as those from adjacent parts of the lateral hypothalamic area. Because of these similarities, the TU may eventually come to be viewed most appropriately as the lateral component of the VMH itself. The functional implications of the present findings are discussed in view of evidence that the VMH plays a role in the expression of ingestive, affective, and copulatory behaviors. © 1994 Wiley-Liss, Inc.     

Projections of the ventral premammillary nucleus.

The projections of the ventral premammillary nucleus (PMv) have been examined with the Phaseolus vulgaris leucoagglutinin (PHAL) method in adult male rats. The results indicate that the nucleus gives rise to two major ascending pathways and a smaller descending pathway. One large ascending pathway terminates densely in most regions of the periventricular zone of the hypothalamus, with the notable exception of the suprachiasmatic, suprachiasmatic preoptic, and median preoptic nuclei. This pathway is in a position to influence directly many cell groups known to regulate anterior pituitary function. The second large pathway ascends through the medial zone of the hypothalamus and densely innervates the ventrolateral part of the ventromedial nucleus and adjacent basal parts of the lateral hypothalamic area, medial preoptic nucleus, principal nucleus of the bed nuclei of the stria terminalis, ventral lateral septal nucleus, posterodorsal part of the medial nucleus of the amygdala, posterior nucleus, and immediately adjacent regions of the posterior cortical nucleus of the amygdala. It is already known that these regions are major components of the sexually dimorphic circuit, and, interestingly, that they provide the major neural inputs to the PMv. The smaller descending projection from the PMv seems to innervate preferentially the posterior hypothalamic nucleus, although a small number of fibers appear to end in the tuberomammillary nucleus, supramammillary nucleus, specific regions of the medial mammillary nucleus, interfascicular nucleus, interpeduncular nucleus, periaqueductal gray, dorsal nucleus of the raphe, laterodorsal tegmental nucleus, Barrington's nucleus, and locus coeruleus. Relatively sparse terminal fields associated with ascending fibers were also observed in the dorsomedial nucleus of the hypothalamus; in the nucleus reuniens, parataenial nucleus, paraventricular nucleus of the thalamus, and mediodorsal nucleus; in the central nucleus of the amygdala, anterodorsal part of the medial nucleus of the amygdala, posterior part of the basomedial nucleus of the amygdala; and in the ventral subiculum and adjacent parts of hippocampal field CA1, and the infralimbic and prelimbic areas of the medial prefrontal cortex. Taken as a whole, the evidence suggests that the PMv receives two major inputs--one from the sexually dimorphic circuit, and the other from the blood in the form of gonadal steroid hormones--and gives rise to two major outputs: one (perhaps feed-forward) to the neuroendocrine (periventricular) zone of the hypothalamus, and the other (perhaps feed-back) to the sexually dimorphic circuit.     

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.     

Septal complex of the telencephalon of lizards: III. Efferent connections and general discussion

The projections of the septum of the lizard Podarcis hispanica (Lacertidae) were studied by combining retrograde and anterograde neuroanatomical tracing. The results confirm the classification of septal nuclei into three main divisions. The nuclei composing the central septal division (anterior, lateral, medial, dorsolateral, and ventrolateral nuclei) displayed differential projections to the basal telencephalon, preoptic and anterior hypothalamus, lateral hypothalamic area, dorsal hypothalamus, mammillary complex, dorsomedial anterior thalamus, ventral tegmental area, interpeduncular nucleus, raphe nucleus, torus semicircularis pars laminaris, reptilian A8 nucleus/ substantia nigra and central gray. For instance, only the medial septal nucleus projected substantially to the thalamus whereas the anterior septum was the only nucleus projecting to the caudal midbrain including the central gray. The anterior and lateral septal nuclei also differ in the way in which their projection to the preoptic hypothalamus terminated. The midline septal division is composed of the dorsal septal nucleus, nucleus septalis impar and nucleus of the posterior pallial commissure. The latter two nuclei projected to the lateral habenula and, at least the nucleus of the posterior pallial commissure, to the mammillary complex. The dorsal septal nucleus projected to the preoptic and periventricular hypothalamus and the anterior thalamus, but its central part seemed to project to the caudal midbrain (up to the midbrain central gray). Finally, the ventromedial septal division (ventromedial septal nucleus) showed a massive projection to the anterior and the lateral tuberomammillary hypothalamus. Data on the connections of the septum of P. hispanica and Gecko gekko are discussed from a comparative point of view and used for better understanding of the functional anatomy of the tetrapodian septum. J. Comp. Neurol. 401:525–548, 1998. © 1998 Wiley-Liss, Inc.     

Neuropeptide organization of the hypothalamic projection to the parabrachial nucleus in the rat

The hypothalamus is a major source of afferents to the parabrachial nucleus (PB), but the neurotransmitters in this pathway are largely unknown. In this study, we examine the neuropeptide immunoreactivities of neurons in the hypothalamus that project to the PB by using the combined retrograde fluorescence-immunofluorescence method. After injections of the fluorescent tracer fast blue into the PB, retrogradely labeled neurons were observed in the paraventricular, dorsomedial, ventromedial, median preoptic, and anteroventral periventricular hypothalamic nuclei; in the dorsal, retrochiasmatic, and lateral hypothalamic areas; and in the medial and lateral preoptic areas. Our results show that at least five distinct neuropeptide-immunoreactive cell populations in the hypothalamus project to the PB. In the perifornical lateral hypothalamus, many neurotensin (NT)-, corticotropin-releasing factor-, dynorphin (DYN)-, angiotensin II (AII)-, and galanin-like immunoreactive (-ir) neurons were retrogradely labeled. A cluster of retrogradely labeled neurons in the juxtacapsular lateral hypothalamus stained with an antiserum against alpha-melanocyte stimulating hormone (alpha MSH). Over 50% of the retrogradely labeled cells in the arcuate nucleus were adrenocorticotropin (ACTH)-or alpha MSH-ir. Many alpha MSH- and ACTH-ir, and a few DYN-, NT- and AII-ir neurons in the retrochiasmatic area were retrogradely labeled. Only small numbers of double-labeled neurons were found in the paraventricular nucleus, and, of these, enkephalin-ir and dynorphin-ir neurons were the most common. Somatostatin-ir cells in the hypothalamus were rarely double-labeled. The chemical coding of these hypothalamic projections to the PB may provide important clues to the functional organization of these descending pathways.     

The hypothalamic ‘tuberoinfundibular’ system of the rat as demonstrated by horseradish peroxidase (HRP) microiontophoresis

Microiontophoresis of horseradish peroxidase (20%) into the median eminence of the rat has allowed visualization of perikarya and axon projections of the tuberoinfundubular system after retrograde transport. Cells projecting to the median eminence were found in the periventricular regions of the hypothalamus and were particularly pronounced in dorsal portions of the rostral arcuate nucleus, the medial division of the paraventricular nucleus, and within the anterior periventricular nucleus. Labeling of perikarya within the ventromedial nucleus was rarely found. No labeling by HRP was found within cells of the dorsomedial, anterior, suprachiasmatic, preoptic, lateral hypothalamic nuclei or within the septal and amygdaloid nuclei. Axons from identifiable cells were located within the periventricular neuropil and contained within the baso-lateral portions of the hypothalamic-hypophysial tract.     

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

Afferent connections to the medial hypothalamic region in the rat were studied using horseradish peroxidase (HRP). HRP was injected iontophoretically by a parapharyngeal approach. After HRP injections into the ventromedial hypothalamic nucleus, labeled cells were found mainly in the medial and basolateral amygdaloid nuclei, subiculum, peripeduncular nucleus and the parabrachial area. Labeled cells following HRP injections into the dorsomedial hypothalamic nucleus were found mainly in the lateral septal nucleus, nucleus accumbens, bed nucleus of the stria terminalis, pontine central gray and the parabrachial area. HRP-labeled cells following the medial preoptic area injections were found mainly in the infralimbic cortex, lateral and medial septal nuclei, nucleus accumbens, diagonal band, bed nucleus of the stria terminalis, medial amygdaloid nucleus, subiculum, peripedunclar nucleus and the parabrachial area. The intrahypothalamic connections were also discussed.     

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.     

Metabolic mapping of the rat brain involved in thermoregulatory responses using the [C]2-deoxyglucose technique

The central nervous structures involved in thermoregulatory responses to thermal stimulation of the preoptic/anterior hypothalamic region were investigated in conscious, unrestrained rats by means of the 2-deoxy-d-[¹⁴C]glucose autoradiographic technique. Significant activation in metabolic activity was observed in the medial preoptic area, medial forebrain bundle, anterior part of ventromedial hypothalamus, anteroventral thalamus, dorsomedial thalamus, basal ganglia, pars compacta of substantia nigra, red nucleus and the reticular formation.     

The efferent connections of the suprachiasmatic nucleus of the hypothalamus

The efferent connections of the suprachiasmatic nucleus of the hypothalamus have been studied in the rat by the injection of ³H-proline into the nucleus and the surrounding regions of the rostral hypothalamus, and by the injection of the enzyme marker, horseradish peroxidase, into the region of the ventromedial hypothalamic nucleus. After an injection of ³H-proline confined to the ventral portion of the suprachiasmatic nucleus, transported label can be followed, in the autoradiographs, dorsally and caudally in the periventricular area as far as the caudal end of the ventromedial nucleus, into the triangular area between this nucleus and the arcuate nucleus, and along the ventral aspect of the tuberal region, just lateral to the ventromedial nucleus. A small number of silver grains are also seen over the internal lamina of the median eminence. No label can be followed rostrally or immediately lateral to the nucleus. Comparable injections into adjoining regions of the hypothalamus (especially the anterior hypothalamic area, the medial preoptic area, and the retrochiasmatic region) show transported label over the same regions, but with a somewhat different pattern of grain distribution; in addition, the anterior hypothalamic area shows an extensive projection through the medial forebrain bundle to the mammillary and supramammillary nuclei, the midbrain tegmentum, and certain of the midline thalamic nuclei. Although it is difficult in our autoradiographs to distinguish between the course of the efferent fibers from the suprachiasmatic nucleus and the zones in which they terminate, our evidence favors a termination among the cells of the periventricular area, and upon dendrites of the cells in the ventromedial, dorsomedial and arcuate nuclei, which extend beyond the limits of the nuclei into the periventricular area and to the area beneath the ventromedial nucleus.     

Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat

The projections of the medial preoptic nucleus (MPN) were examined by making injections of the anterogradely transported lectin Phaseolus vulgaris leucoagglutinin (PHA-L) into the MPN and charting the distribution of labeled fibers. The evidence indicates that the MPN projects extensively to widely distributed regions in both the forebrain and brainstem, most of which also supply inputs to the nucleus. An important neuroendocrine role for the MPN is underscored by its extensive projections to almost all parts of the periventricular zone of the hypothalamus, including the anteroventral periventricular, anterior part of the periventricular, paraventricular (PVH), and arcuate nuclei, and a role in autonomic mechanisms is indicated by projections to such regions as the dorsal and lateral parvicellular parts of the PVH, the lateral parabrachial nucleus, and the nucleus of the solitary tract. Other projections of the MPN suggest participation in the initiation of specific motivated behaviors. For example, inputs to two nuclei of the medial zone of the hypothalamus, the ventromedial and dorsomedial nuclei, may be related to the control of reproductive and ingestive behaviors, respectively, although the possible functional significance of a strong projection to the ventral premammillary nucleus is presently unclear. The execution of these behaviors may involve activation of somatomotor regions via projections to the substantia innominata, zona incerta, ventral tegmental area, and pedunculopontine nucleus. Similarly, inputs to other regions that project directly to the spinal cord, such as the periaqueductal gray, the laterodorsal tegmental nucleus, certain medullary raphe nuclei, and the magnocellular reticular nucleus may also be involved in modulating somatic and/or autonomic reflexes. Finally, the MPN may influence a wide variety of physiological mechanisms and behaviors through its massive projections to areas like the ventral part of the lateral septal nucleus, the bed nucleus of the stria terminalis, the lateral hypothalamic area, the supramammillary nucleus, and the ventral tegmental area, all of which have extensive connections with regions along the medial forebrain bundle. Although the PHA-L method does not allow a clear demonstration of possible differential projections from each subdivision of the MPN, our results suggest that each of them does give rise to a unique pattern of outputs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Norepinephrine and dopamine content of hypothalamic nuclei of the rat

The concentrations of norepinephrine and dopamine of 27 isolated rat hypothalamic nuclei or nuclear subdivisions have been determined using an enzymatic-isotopic assay. The hypothalamic nuclei contain 3–20 times more NE and DA than is measured in the cortex. They are distributed unevenly throughout the hypothalamus and individual hypothalamic nuclei are heterogenous as regards their content of the amines.The dopamine content of the median eminence is among the highest measured in the brain (65 ng/mg protein). The norepinephrine content is about half that of dopamine.All of the hypothalamic nuclei contain dopamine. It is highly concentrated in the rostral subdivisions of the arcuate nucleus, the paraventricular and dorsomedial nuclei, the retrochiasmatic area, the medial posterior subdivision of the ventromedial nucleus and in the medial forebrain bundle at the posterior hypothalamic level.The highest concentrations of norepinephrine were found in the paraventricular and dorsomedial nuclei and in the retrochiasmatic area. The rostal subdivision of the arcuate nucleus and the periventricular and preoptic suprachiasmatic nuclei are also rich in norepinephrine.The posterior hypothalamus (premammillary nuclei, caudal subdivision of the arcurate nucleus, posterior hypothalamic nucleus) contains norepinephrine and dopamine in relatively low concentrations.     

Basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain.

The organization of axonal projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis (BST) was characterized with the Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracing method in adult male rats. Within the BST, the oval nucleus (BSTov) projects very densely to the fusiform nucleus (BSTfu) and also innervates the caudal anterolateral area, anterodorsal area, rhomboid nucleus, and subcommissural zone. Outside the BST, its heaviest inputs are to the caudal substantia innominata and adjacent central amygdalar nucleus, retrorubral area, and lateral parabrachial nucleus. It generates moderate inputs to the caudal nucleus accumbens, parasubthalamic nucleus, and medial and ventrolateral divisions of the periaqueductal gray, and it sends a light input to the anterior parvicellular part of the hypothalamic paraventricular nucleus and nucleus of the solitary tract. The BSTfu displays a much more complex projection pattern. Within the BST, it densely innervates the anterodorsal area, dorsomedial nucleus, and caudal anterolateral area, and it moderately innervates the BSTov, subcommissural zone, and rhomboid nucleus. Outside the BST, the BSTfu provides dense inputs to the nucleus accumbens, caudal substantia innominata and central amygdalar nucleus, thalamic paraventricular nucleus, hypothalamic paraventricular and periventricular nuclei, hypothalamic dorsomedial nucleus, perifornical lateral hypothalamic area, and lateral tegmental nucleus. Moderately dense inputs are found in the parastrial, tuberal, dorsal raphé, and parabrachial nuclei and in the retrorubral area, ventrolateral division of the periaqueductal gray, and pontine central gray. Light projections end in the olfactory tubercle, lateral septal nucleus, posterior basolateral amygdalar nucleus, supramammillary nucleus, and nucleus of the solitary tract. These and other results suggest that the BSTov and BSTfu are basal telencephalic parts of a circuit that coordinates autonomic, neuroendocrine, and ingestive behavioral responses during stress.     

Indirect projections from the suprachiasmatic nucleus to the ventrolateral preoptic nucleus: a dual tract-tracing study in rat

The suprachiasmatic nucleus (SCN) contains a master clock for most circadian rhythms in mammals, including daily sleep-wake cycles. The ventrolateral preoptic nucleus (VLPO) plays a key role in sleep generation and, as such, might be an important target of the SCN circadian signal. However, direct SCN projections to the VLPO are limited, suggesting that most of the SCN output to the VLPO might be conveyed indirectly. We examined this possibility by microinjecting selected known major targets of SCN efferents with biotinylated dextran-amine and/or cholera toxin B subunit, followed by analyses of retrograde labelling in the SCN and anterograde labelling in the VLPO. Retrograde labelling results confirmed that the medial preoptic area, subparaventricular zone, dorsomedial hypothalamic nucleus and posterior hypothalamic area all received projections from the SCN; these projections arose predominantly from the shell, as opposed to the core, of the SCN. Anterograde labelling results indicated that these same nuclei also projected to the VLPO, mainly its medial and ventral aspects. Comparison of the results of injections of similar sizes across different target groups indicated that the rostral part of the medial preoptic area and the caudal part of the dorsomedial hypothalamic nucleus were particularly noteworthy for the abundance of both SCN source neurons and efferent fibres and terminals in the VLPO. These results suggest that the SCN might provide indirect input to the VLPO via the medial preoptic area and the dorsomedial hypothalamic nucleus, and that these indirect neuronal pathways might play a major role in circadian control of sleep-wake cycles.     

Efferent projections of the infralimbic cortex of the rat.

On the basis of stimulation studies, it has been proposed that the infralimbic cortex (ILC), Brodmann area 25, may serve as an autonomic motor cortex. To explore this hypothesis, we have combined anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde tracing with wheat germ aggutinin conjugated to horseradish peroxidase (WGA-HRP) to determine the efferent projections from the ILC. Axons exit the ILC in one of three efferent pathways. The dorsal pathway ascends through layers III and V to innervate the prelimbic and anterior cingulate cortices. The lateral pathway courses through the nucleus accumbens to innervate the insular cortex, the perirhinal cortex, and parts of the piriform cortex. In addition, some fibers from the lateral pathway enter the corticospinal tract. The ventral pathway is by far the largest and innervates the thalamus (including the paraventricular nucleus of the thalamus, the border zone between the paraventricular and medial dorsal nuclei, and the paratenial, reuniens, ventromedial, parafasicular, and subparafasicular nuclei), the hypothalamus (including the lateral hypothalamic and medial preoptic areas, and the suprachiasmatic, dorsomedial, and supramammillary nuclei), the amygdala (including the central, medial, and basomedial nuclei, and the periamygdaloid cortex) and the bed nucleus of the stria terminalis. The ventral efferent pathway also provides descending projections to autonomic cell groups of the brainstem and spinal cord including the periaqueductal gray matter, the parabrachial nucleus, the nucleus of the solitary tract, the dorsal motor vagal nucleus, the nucleus ambiguus, and the ventrolateral medulla, as well as lamina I and the intermediolateral column of the spinal cord. The ILC has extensive projections to central autonomic nuclei that may subserve a role in modulating visceral responses to emotional stimuli, such as stress.