Premammillary Nucleus


Previous studies from our laboratory have documented that the medial hypothalamic defensive system is critically involved in processing actual and contextual predatory threats, and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats.  

The premammillary nucleus (PMM) has been shown to contain a daily endogenous dual-oscillation in dopamine (DA)/melatonin (MEL) as well as c-fos mRNA expression that is associated with the daily photo-inducible phase of gonad growth in turkeys.  

At the light microscopic level, NPW-like immunoreactive (NPW-LI) cell bodies were found in the preoptic area (POA), PVN, ARC, VMH, LH, PMD (dorsal premammillary nucleus), periaqueductal gray (PAG), lateral parabrachial nucleus (LPB), and prepositus nucleus (Pr).  

Additionally, using injections of retrograde tracers we found that CART neurons in the ventral premammillary nucleus also innervate the MPO. The MPO densely innervates hypothalamic nuclei related to reproductive control including the anteroventral periventricular nucleus, the ventrolateral subdivision of the ventromedial nucleus (VMHvl) and the ventral premammillary nucleus (PMV).  

NK3R cells and/or fibres were found in areas including the bed nucleus of the stria terminalis, POA, anterior hypothalamic and perifornical areas, dopaminergic A15 region, dorsomedial and lateral hypothalamus, arcuate nucleus (ARC) and the ventral premammillary nucleus.  

Studies have shown that the medial nucleus of the amygdala (MEA) and the ventral premammillary nucleus (PMV) are recruited by conspecific odor stimulation.  

Up-regulation of FosB/DeltaFosB was observed 24h after repeated cat odor exposure in the nucleus accumbens core, caudate putamen, ventrolateral periaqueductal gray, and four hypothalamic regions: lateral hypothalamus, ventromedial hypothalamus, anterior hypothalamic nucleus, and dorsal premammillary nucleus.  

The expression of Kiaa2022 is first detectable at E10.5 to reach a maximum at P3 where it is notably expressed in the hippocampus, the entorhinal cortex and strongly in the ventral premammillary nucleus.  

Older rats had reduced Fos expression in several defense-related brain regions that are normally activated by predator odors such as the medial amygdala and dorsal premammillary nucleus.  

The hypothalamic ventral premammillary nucleus (PMV) neurons express a dense concentration of leptin receptors and project to brain areas related to reproductive control.  

Cat exposure induced fear responses and an increase of FLI in the dlPAG and dorsal premammillary nucleus (PMd).  

We found substantial LepRb mRNA and EYFP expression in hypothalamic and extrahypothalamic sites described before, including the dorsomedial nucleus of the hypothalamus, ventral premammillary nucleus, ventral tegmental area, parabrachial nucleus, and the dorsal vagal complex.  

The very strong innervation of the ventral premammillary nucleus further indicated the involvement of the MePD in the neuronal circuitry for sexual behavior.  

The ventral premammillary nucleus of the hypothalamus (PMv), which has been implicated in the stimulation of gonadotropin release by olfactory cues, contains numerous LepRb neurons, suggesting a potential role for LepRb PMv neurons in transmitting both metabolic and odorant signals to the neuroendocrine reproductive system.  

The results of behavioral, neuronal immediate early gene activation, lesion, and neuroanatomical experiments indicate that the hypothalamus is necessary for full expression of defensive behavioral responses in a subordinate conspecific, that lesions of the dorsal premammillary nucleus drastically reduce behavioral measures of fear in these animals, and that essentially separate hypothalamic circuitry supports defensive responses to a predator or a dominant conspecific.  

Utilizing in situ hybridization, immunocytochemistry and reverse transcriptase-polymerase chain reaction techniques, a group of dopamine (DA) neurons in the premammillary nucleus (PMM) of the caudal turkey hypothalamus that synthesize and colocalize both DA and melatonin (MEL) were identified.  

Lmx1a was expressed at high levels in the posterior hypothalamic area, supremammillary nucleus, ventral premammillary nucleus, subthalamic nucleus, ventral tegmental area, compact part of the substantia nigra and parabrachial nucleus from birth to adulthood, and co-localized with its paralogue Lmx1b in these regions.  

Our previous studies have shown that co-localised dopamine-melatonin (DA-MEL) neurones in the avian premammillary nucleus (PMM) are active during periods of photoresponsiveness and, therefore, are potentially photosensitive neurones.  

Next, we examined the neural substrate underlying the noradrenergic modulation of the defensive response to cat odor and focused on the dorsal premammillary nucleus (PMd), because it represents the hypothalamic site most responsive to predatory threats and, at the same time, presents a dense plexus of noradrenergic fibers.  

Our results support the view that hypothalamic processing of the actual and the contextual predatory threats share the same circuit, in which the dorsal premammillary nucleus (PMd) plays a pivotal role in amplifying this processing.  

Researchers are beginning to identify brain sites associated with conditioned contextual fear such as the ventral anterior olfactory nucleus, dorsal premammillary nucleus, ventrolateral periaqueductal gray, cuneiform nucleus, and locus coeruleus.  

The dorsal premammillary nucleus (PMd) has a critical role on the expression of defensive responses to predator odor.  

At postnatal day (P) 7, many Lmx1b-expressing neurons were found in the posterior hypothalamic area, supramammillary nucleus, ventral premammillary nucleus, and subthalamic nucleus.  

It was then identified in medial preoptic area, anterior hypothalamus, retrochiasmatic area, dorsomedial nucleus and premammillary nucleus from P7, and in ventromedial nucleus and lateral hypothalamus from P11.  

Of particular note, similar to what has been described for the rat, we observed in the mouse that predator exposure induces a striking activation in the elements of the medial hypothalamic defensive system, namely, the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus.  

All animals had AR+ nuclei in many of the same regions positive for AR in other mammals, including the VMH, BST, PVN, MeA, and the ventral portion of the premammillary nucleus (PMv).  

Recent findings from our laboratory provide data showing dopamine (DA) neurons within the premammillary nucleus (PMM) of the caudal turkey hypothalamus are putative photoreceptive neurons.  

Studies have shown that female odors induce Fos expression in various brain nuclei of conspecific males, including the ventral premammillary nucleus (PMV).  

Fibers immunoreactive to Ucn 3 are confined to certain brain nuclei, being particularly dense in the ventral premammillary nucleus (PMV).  

Exposure to the EPM significantly increased double-stained cells (c-Fos + NADPHd positive neurons) in the parvocellular paraventricular (pPVN) and lateral (LH) hypothalamic nuclei, dlPAG and dorsal raphe nucleus (DRN), but not in the amygdaloid complex, bed nucleus of stria terminallis, dorsal premammillary nucleus of hypothalamus and inferior colicullus.  

The former include inputs to anterior hypothalamic nucleus, dorsomedial part of the ventromedial nucleus, and ventral region of the dorsal premammillary nucleus (defensive behavior control system components), and to lateral habenula and dorsal region of the dorsal premammillary nucleus (foraging behavior control system components).  

The context-exposed group showed Fos expression in a subset of the regions activated by cat odor itself: the dorsal premammillary nucleus, ventrolateral periaqueductal grey, cuneiform nucleus and locus ceruleus.  

A review of the brain regions involved in predator odor-induced fear behavior indicates a modulatory role of the medial amygdala, bed nucleus of the stria terminalis, and dorsal premammillary nucleus.  

Both electrolytic and neurotoxic lesions of the dorsal premammillary nucleus, which shows the strongest Fos response to cat exposure, produce striking decrements in a number of defensive behaviors to a cat or to cat odor stimuli, but do not have a major effect on either postshock freezing, or responsivity to the odor of a female in estrus. These results support the view that the dorsal premammillary nucleus is strongly and selectively involved in control of responsivity to predator stimuli.  

Distinct clusters of CRF-BP-ir neurones were identified in the anterior and posterior parvocellular and dorsal cap subdivisions of the paraventricular nucleus (PVN), as well as in the dorsal hypothalamic area, dorsomedial hypothalamic nucleus (DMN), ventral premammillary nucleus and zona incerta.  

Previous studies have shown that electrolytic lesions of the dorsal premammillary nucleus (PMd) produce robust reductions in responsivity of rats to the presence of a live predator as well as to its odor, suggesting a critical role for the PMd in the modulation of defense.  

Midazolam inhibited Fos expression in key limbic regions involved in pheromone transduction (medial amygdala and bed nucleus of the stria terminalis) and defensive behavior (prelimbic cortex, lateral septum, lateral and medial preoptic areas, and dorsal premammillary nucleus). These results indicate that midazolam exerts a region-specific effect on the neural substrates activated by predator odor, with effects in the lateral septum and dorsal premammillary nucleus likely to be of major importance.  

In the arcuate nucleus, dorsomedial nucleus of the hypothalamus, and ventral premammillary nucleus, CART neurons also express leptin receptor long-form splice-variant. As a control, we injected the anterograde tracer biotinylated dextran amine into the ventral premammillary nucleus of both males and females. Our findings indicate that ventral premammillary nucleus CART neurons intermingle with brain circuitry involved in reproduction.  

By combining immunocytochemistry for NeuN, a neuronal marker, with Nissl staining in anestrous, ovariectomized, estradiol-treated ewes, we identified three nuclei within the PMH: a caudal continuation of the hypothalamic arcuate nucleus (cARC), the ventral division of the premammillary nucleus (PMv), and the ventral tuberomammillary nucleus (TMv).  

Predator-specific c-fos mRNA induction was observed in several brain regions comprising the hypothetical brain defense circuit (bed nucleus of the stria terminalis, medial region of the ventromedial nucleus, and dorsal premammillary nucleus).  

Lesions of the dorsal premammillary nucleus (PMd) have been reported to produce dramatic reductions in responsivity of rats to a live cat.  

Retrogradely radiolabelled neurons in various numbers were detected in several brain regions including medial septum-diagonal band complex, lateral septum, rostral part of medial and lateral preoptic areas, lateral habenula, ventral premammillary nucleus, apical subregion of interpeduncular nucleus, laterodorsal tegmental nucleus, and dorsal and median raphe nuclei.  

Thus, after exposure to a natural predator known to elicit innate defensive responses, increased Fos levels in the medial zone of the hypothalamus have been found restricted to the anterior hypothalamic nucleus, dorsomedial part of the ventromedial nucleus, and dorsal premammillary nucleus (PMd).  

Hypothalamic regions that were innervated prominently by Ucn III fibers included the ventromedial nucleus, medial preoptic nucleus, and ventral premammillary nucleus.  

The dorsal premammillary nucleus (PMd) is thought to play a critical role in the expression of fear responses to environmental threats.  

C-fos immunohistochemistry indicates that cat odor selectively activates a defensive behavior circuit involving the medial amygdala, ventromedial and dorsomedial hypothalamus, dorsal premammillary nucleus and the periaqueductal gray.  

Furthermore, we have recently shown that these and other regions, such as the principal bed nucleus of the stria terminalis, the ventral lateral septum, and the dorsal premammillary nucleus, show higher pup-induced Fos-immunoreactivity in non-maternal rats exposed to pups than during the performance of maternal behavior, indicating that they too could be involved in preventing maternal responsiveness. Unilateral medial amygdala lesions caused a reduction of pup-induced Fos-immunoreactivity in the anterior/ventromedial hypothalamic nuclei in non-maternal rats ipsilateral to the lesion, as well as in the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus. Finally, unilateral medial amygdala lesions paired with contralateral anterior/ventromedial hypothalamic nuclei lesions promoted maternal behavior, although ipsilateral lesion placements were also effective.Together, these results indicate that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, and that the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus could also be involved in this circuit..  

Within the brain, labeling for AR mRNA was conspicuous in the anterior olfactory nucleus, the lateral septum, the medial preoptic area, the periventricular preoptic area, the external nucleus of the amygdala, the anterior hypothalamus, the ventromedial hypothalamus, the premammillary nucleus, and the caudal portion of the periventricular nucleus of the hypothalamus.  

OX(2)R mRNA was prominent in a complementary distribution including the cerebral cortex, septal nuclei, hippocampus, medial thalamic groups, raphe nuclei, and many hypothalamic nuclei including the tuberomammillary nucleus, dorsomedial nucleus, paraventricular nucleus, and ventral premammillary nucleus.  

CART mRNA and peptides are found in hypothalamic sites such as the paraventricular nucleus (PVH), the supraoptic nucleus (SON), the lateral hypothalamic area (LHA), the dorsomedial nucleus of the hypothalamus (DMH), the arcuate nucleus (Arc), the periventricular nucleus (Pe), and the ventral premammillary nucleus (PMV).  

Labelled neurons were detected in the paraventricular nucleus itself, in several hypothalamic areas including medial and lateral preoptic area, suprachiasmatic nucleus, anterior hypothalamic area, ventromedial nucleus, dorsomedial nucleus, lateral hypothalamic area, posterior part of arcuate nucleus, ventral premammillary nucleus and supramammillary nucleus.  

In the male Eastern Fence lizard, AR-immunoreactive (-ir) nuclei were observed in the medial preoptic area, ventromedial and arcuate hypothalamic nuclei, periventricular hypothalamus, premammillary nucleus, bed nucleus of the stria terminalis, and ventral posterior amygdala.  

The induction of Fos-IR was observed in hypothalamic nuclei, including the paraventricular nucleus (PVH), the retrochiasmatic area (RCA), the ventromedial nucleus (VMH), the dorsomedial nucleus (DMH), the arcuate nucleus (Arc), and the ventral premammillary nucleus (PMV).  

The dorsal premammillary nucleus (PMd) is thought to play a critical role for the expression of fear responses to environmental threats.  

For others, such as the ventral lateral septum, dorsal premammillary nucleus, and principal bed nucleus of the stria terminalis, this is the first indication that they could also inhibit maternal responding.  

Previous studies have indicated that the ventral part of the premammillary nucleus (PMv) of rodents is involved in the regulation of aggressive and male mating behavior, although the precise physiological function of the PMv is still unclear.  

CARTir neurons were particularly abundant in the PVN, supraoptic nucleus (SON), infundibular nucleus, and premammillary nucleus, whereas the anterior, lateral, and posterior hypothalamic areas as well as the posterior nucleus displayed moderate immunoreactivity.  

Other retrogradely labeled neurons were observed in the taenia tecta, the septum, the nucleus of the lateral olfactory tract, the preoptic area, the lateral hypothalamic area, the mediobasal hypothalamus, the lateral part of the premammillary nucleus, the paraventricular nucleus of the hypothalamus, the paraventricular thalamic nucleus, the central grey, the substantia nigra (SN), the ventral tegmental area (VTA), the lateral nucleus to the interpeduncular nucleus (IIP), the raphe and the locus coeruleus (LC).  

In the ventral premammillary nucleus, ventromedial nucleus of the hypothalamus, and medial amygdaloid nucleus, androgen receptor staining was similar in gonadectomized males and females.  

Thus, we have shown that the nucleus receives substantial inputs from the prefrontal cortex, specific domains of the rostral part of the lateral septal nucleus, rostral zona incerta, perifornical region, anterior hypothalamic nucleus, ventromedial hypothalamic nucleus, dorsal premammillary nucleus, medial regions of the intermediate and deep layers of the superior colliculus, and cuneiform nucleus.  

Intense EP3R-like immunoreactivity was observed in the median preoptic nucleus, medial preoptic area, parastrial nucleus, compact part of the dorsomedial hypothalamic nucleus, and dorsal part of the premammillary nucleus.  

Conversely, large numbers of small neurons immunoreactive for aromatic L-amino acid decarboxylase but not for tyrosine hydroxylase, were identified in the premammillary nucleus (D8), zona incerta (D10), lateral hypothalamic area (D11), anterior portion of the dorsomedial nucleus (D12), suprachiasmatic nucleus (D13), medial preoptic area and bed nucleus of the stria terminalis (D14).  

Retrograde labels by Nuclear Yellow from the female rat ventral premammillary nucleus (PMv) were most numerous in the lateral septum (LS) and the preoptic area (POA) and spread laterally into the substantia innominata.  

At that time sex differences had already been described for some structures that receive VNO input, such as the medial amygdala, the medial preoptic area, the ventromedial hypothalamic nucleus, and the ventral region of the premammillary nucleus.  

The dorsal premammillary nucleus showed the most striking increase in Fos levels, and cell body-specific chemical lesions therein virtually eliminated two major components of defensive behavior but increased exploratory behavior, suggesting that this caudal hypothalamic nucleus plays a critical role in the expression of behavioral responses sometimes critical for survival of the individual.  

In addition, Fos immunoreactivity in females was induced in the ventrolateral part and the most caudoventral part of the ventromedial nucleus of the hypothalamus and in the premammillary nucleus. This was observed especially in the posteromedial bed nucleus of the stria terminalis and posterodorsal medial amygdala, but also in the parvicellular subparafascicular nucleus, ventromedial hypothalamic nucleus and ventral premammillary nucleus.  

Many NOS-positive neurons in the posterior subdivision of the Me, the medial preoptic nucleus (MPN), and the ventral premammillary nucleus contain androgen receptors.  

The area dorsal to the medial part of the sexually dimorphic area, the paraventricular nucleus of the hypothalamus, the ventral premammillary nucleus and the retrorubral field showed the same level of c-Fos expression when males were exposed to the non-sexual context as when they were exposed to the sexual one.  

The following regions receive strong projections: lateral septum, substantia innominata, paraventricular hypothalamic nucleus, ventral premammillary nucleus, supramammillary nucleus, paraventricular thalamus, ventral tegmental area, periaqueductal gray, retrorubral field, and the region surrounding the locus coeruleus..  

The highest number of immunoreactive cells were present in the dorsal and ventral nuclei of the lateral septum, medial division of the bed nucleus of the stria terminalis, medial preoptic area, median preoptic nucleus, nucleus of the lateral olfactory tubercle, central amygdaloid nucleus, anterior cortical amygdaloid nucleus, posterior amygdaloid nucleus, subiculum, ventromedial hypothalamic nucleus, arcuate-median eminence region, and ventral premammillary nucleus.  

Single-labelled estrogen receptor-containing neurons were most numerous in the amygdalohippocampal area and the rostral medial preoptic nucleus; androgen receptor-immunoreactive cells were most abundant in the ventral premammillary nucleus and the lateral septum.  

The pattern of PA1 ARir labeling was closely similar between animals and occurred in the lateral septum, medial preoptic area, bed nucleus of stria terminalis, anterior, cortical, accessory basal and medial amygdala, several hypothalamic nuclei including the supraoptic, anterior, paraventricular, ventromedial and arcuate nuclei, and the premammillary nucleus.  

Agonistic behavior increased the number of Fos-immunoreactive neurons within most subdivisions of the medial amygdala, the anteromedial and posterointermediate bed nucleus of the stria terminalis, the ventrolateral septum and the ventral premammillary nucleus of the hypothalamus in a pattern comparable to that observed after mating.  

Pre-PDYN message is especially abundant in neurons of the tuberal and mammillary regions, with a distinct population of labeled cells in the premammillary nucleus and dorsal posterior hypothalamus.  

High SSTR1, but low SSTR2, expression was evident in the para- and periventricular nuclei as well as in the ventral premammillary nucleus.  

High sstr1, but low sstr2, expression was evident in the paraventricular and periventricular nuclei as well as in the ventral premammillary nucleus.  

Dorsal route fibers provide inputs to the zona incerta and posterior hypothalamic nucleus, whereas more ventral axons generate dense terminal fields in the ventromedial nucleus capsule and core, and dorsal premammillary nucleus.  

The results of double-staining by the immunofluorescence method as well as immunoelectron microscopy strongly indicate that the cells of the premammillary nucleus of the laboratory shrew brain (AADC-only-positive neurons) are capable of synthesizing DA and 5-HT simultaneously upon simultaneous administration of L-dopa and 5-HTP..  

In the hypothalamus, in addition to the perifornical region, retrogradely labeled neurons were found in all cases in the tuberomammillary nucleus, premammillary nucleus, dorsal hypothalamic area, ventromedial hypothalamic nucleus, and the paraventricular nucleus.  

Medial cuts also labeled more cells in the ventral part of the lateral septal nucleus, the encapsulated part of the bed nucleus of the stria terminalis, the medial nucleus of the amygdala, the amygdalohippocampal area, and the ventral premammillary nucleus than lateral cuts did.  

Some of these areas, as for instance the dorsomedial thalamic nucleus, septum and central gray, are innervated by efferents from the hypothalamic attack area, whereas other sites, like ventral premammillary nucleus and ventral tegmental area, are not.  

On the contrary, in the premammillary nucleus no significant differences were noticed following castration and testosterone treatment. Our observations suggest that, in adult Siberian hamster premammillary nucleus, the expression of vasopressin receptors is not controlled by gonadal steroids but is sex related and could be induced during fetal or early postnatal life..  

It was also labeled from the vascular organ of the lamina terminalis, the caudal part of the lateral bed nucleus of the stria terminalis, the lSDA, the area lateral to the mSDA, the arcuate nucleus, the ventral premammillary nucleus, and the ventrolateral part of the ventromedial nucleus of the hypothalamus.  

In addition, a cell group lacking detectable catecholamine fluorescence in normal animals but accumulating L-DOPA after peripheral loading was identified and characterized from a morphometric standpoint in the ventral premammillary nucleus.  

The supramammillary nucleus also receives a few (but distinct) fibers from the anterior and lateral hypothalamic nuclei, the ventral premammillary nucleus, the interpeduncular nucleus, the cuneiform nucleus, the dorsal raphe nucleus, the incertus nucleus, and the C3 region including the prepositus hypoglossi nucleus.  

Strong connections with sexually dimorphic nuclei suggest that the ventral premammillary nucleus (PMv) may be involved in the mediation of reproductive behavior.  

This hypothesis sprung from several facts; (a) the existence of steroid receptors in the VNS; (b) sexual dimorphism was already described in some structures that receive vomeronasal input, such as the medial preoptic area, the ventromedial hypothalamic nucleus, the ventral region of the premammillary nucleus and the medial amygdaloid nucleus; and (c) the vomeronasal organ, which is the receptor organ of the VNS, was also sexually dimorphic.  

The results of anterograde and retrograde axonal transport experiments in the rat indicate that the dorsal premammillary nucleus (PMd) gives rise to a branched pathway ending in the anterior thalamic group and brainstem, like the medial and lateral mammillary nuclei.  

The projections of the ventral premammillary nucleus (PMv) have been examined with the Phaseolus vulgaris leucoagglutinin (PHAL) method in adult male rats.  

The medial corticohypothalamic tract is the main route taken by fibers from the ventral subiculum to the hypothalamus, where they innervate the medial preoptic area, "shell" of the ventromedial nucleus, dorsomedial nucleus, ventral premammillary nucleus, and cell-poor zone around the medial mammillary 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. 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.  

Anatomically matched tissue sections (11 per animal, from the retrochiasmatic region rostrally to the premammillary nucleus caudally) were exposed to x-ray film, followed by densitometric analysis.  

A few TH-positive neurons were also identified in the dorsal and ventral premammillary nucleus, as well as the lateral hypothalamic area.  

Attention was focused on [ 3H]vasopressin binding sites located in the hypothalamic ventromedial nucleus, medial tuberal nucleus, and ventral premammillary nucleus in males or females kept in long or short photoperiod conditions. Quantitative data obtained with a gaseous detector of beta-particles indicated that in the ventromedial nucleus and in the ventral premammillary nucleus of animals in long photoperiod, the number of beta-particles emitted per unit area was significantly greater in males than in females. In the ventral premammillary nucleus, shortening of the photoperiod had a significant effect in reducing the amount of [ 3H]vasopressin bound in females, but not in males.  

These areas include the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, periventricular preoptic area and hypothalamus, amygdala, dorsomedial and ventromedial hypothalamic nuclei, arcuate nucleus, ventral premammillary nucleus, and the midbrain central grey.  

A large number of ER-LI cell nuclei were observed in the medial preoptic area, ventral septal nucleus, medial division of the bed nucleus of the stria terminalis, lateral part of the ventromedial hypothalamus, premammillary nucleus, arcuate nucleus, posterior amygdaloid nucleus, and the midbrain central grey.  

A dense innervation was visualized in; neocortical layers II-III, piriform cortex, the medial amygdala, the medial preoptic area, a circumventricular organ-like structure located at the top of the third ventricle in the preoptic area, the subfornical organ, the posterior bed nucleus of the stria terminalis, the posterior globus pallidus (containing labeled woolly fiber-like profiles), the ventromedial hypothalamus, the median eminence, and the premammillary nucleus.  

Retrogradely labelled cells were also observed in a number of regions for which anterograde tracing data are not available, including the perifornical hypothalamic nucleus, ventral premammillary nucleus, supramammillary and submammillothalamic nuclei and the B9 area.  

Animals pretreated with intracerebroventricular colchicine displayed significantly increased nerve growth factor receptor immunoreactivity in all previously positive neurons and particularly in the medial preoptic area and ventral premammillary nucleus of the hypothalamus.  

Knife cuts of the stria terminalis or extensive electrolytic lesions of the amygdala resulted in the bleaching of the staining for zinc (Timm stain) and terminal degeneration (Fink-Heimer method) ipsilaterally in the following areas: granule cell layer of the accessory olfactory bulb, shell of nucleus accumbens, bed nucleus of the stria terminalis, striohypothalamic nucleus, retrochiasmatic area, ventromedial hypothalamic nucleus (in the cell-sparse shell), medial tuberal nucleus, terete hypothalamic nucleus, and ventral premammillary nucleus. Small lesions made with ibotenic acid in the posteromedial part of the amygdalohippocampal area caused bleaching of the stain for zinc in the accessory olfactory bulb, in the medial zone of the bed nucleus of the stria terminalis, and in the ventral premammillary nucleus.  

Some nearby nuclei (such as the dorsal premammillary nucleus) had smaller numbers of neurons with low levels of CCK mRNA, whereas others (such as the ventral premammillary nucleus) had none..  

Injections of HRP (horseradish peroxidase) into the AV resulted in labeling of the MM (medial mammillary nucleus pars medialis) and MMC (medial mammillary nucleus pars centralis) but not the PM (premammillary nucleus).  

In addition, retrograde labeling suggested that the ventral part of the premammillary nucleus projects more strongly to the medial than to the lateral SDA, whereas the infralimbic area of the cortex and the lateral preoptic area project more strongly to the lateral than to the medial SDA.  

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 ventral premammillary nucleus was observed to have both populations but coexistence was comparatively infrequent (2.4%).  

GRF-i neuronal terminals were seen in the external zone of the median eminence, more rostrally in the periventricular nucleus, and near the suprachiasmatic nucleus and more caudally in the dorsomedial nucleus and ventral premammillary nucleus..  

This nucleus also projects topographically to the ipsilateral dorsal premammillary nucleus; the rostral part of the ventral tegmental nucleus projects to the dorsal part of the dorsal premammillary nucleus, whereas the caudal part projects to the ventral part.  

Destruction of the dorsal premammillary nucleus and medial mammillary nucleus pars medialis, which contained a large group of L-ENKLI neurons, markedly reduced L-ENKLI fibers in the ipsilateral VT, suggesting that most of these fibers originate in these nuclei.  

Sites containing cholinergic neurons of varying density were: medial and lateral preoptic areas, septohypothalamic nucleus, median preoptic area, lateral hypothalamus including the perifornical area, anterior hypothalamic nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, posterior hypothalamic nucleus, dorsal and ventral premammillary nuclei, neuropil mediodorsal to the anterior hypothalamic nucleus, neuropil ventral to the anterior hypothalamic nucleus and ventromedial hypothalamic nucleus, neuropil between lateral hypothalamus and ventromedial hypothalamus, and neuropil between dorsal premammillary nucleus and posterior hypothalamic nucleus.  

Transection of the brain at the level of the premammillary nucleus, mammillary body and superior colliculus caused the appearance of fibers accumulating EnkI in the posterior hypothalamic nucleus (PH), central gray matter medial to the fasciculus retroflexus Mynert and in the DCG, respectively.  

Retrogradely labelled cells were also located bilaterally in the premammillary nucleus, paraventricular hypothalamic nucleus, zona incerta, and lateral habenular nucleus.  

Rats pretreated with intraventricular colchicine for 48 h showed localization of GRF-containing cell bodies in the arcuate nucleus, the perifornical area, the lateral basal hypothalamic region and lateral to the ventromedial nucleus and the premammillary nucleus.  

Within the corticomedial amygdala the medial amygdaloid nucleus was found to be a major recipient of afferents from the accessory olfactory bulb, but also a source of efferent projections to the ventrolateral aspects of the ventromedial hypothalamic nucleus and the ventral premammillary nucleus. The connections between the ventromedial hypothalamic and dorsal premammillary nucleus with the midbrain periaqueductal grey suggest an important role for the periaqueductal gray in the descending output in the anatomical substrate for agonistic behavior..  

In addition, we found reciprocal connections with septo-hypothalamic nucleus, amygdalo-hipocampal nucleus, subiculum, parafascicular thalamic nucleus, posterior thalamic nucleus at the caudo-ventral subdivision, median preoptic nucleus, lateral preoptic nucleus, anterior hypothalamic nucleus, periventricular area at the caudal hypothalamic level, dorsomedial hypothalamic nucleus, posterior hypothalamic nucleus, dorsal and ventral premammillary nucleus, lateral mammillary nucleus, peripeduncular nucleus, periventricular gray, ventral tegmental area, interpeduncular nucleus, nucleus raphe pontis, nucleus raphe magnus, pedunculo-pontine tegmental nucleus, gigantocellular reticular nucleus and solitary tract nucleus.  

One week before the experiments, bipolar concentric stimulating electrodes were implanted in the organum vasculosum of the lamina terminalis (OVLT), the periventricular nucleus of the hypothalamus (Pe), the ventromedial nucleus of the hypothalamus (VMH), the lateral hypothalamic area (LHA), or the ventral premammillary nucleus (PMV).  

Electrochemical stimulation (anodic d.c., 100 microA, 15 s) applied at noon of pro-oestrus to the ventral premammillary nucleus, dorsal premammillary nucleus or posterior hypothalamic nucleus prevented ovulation and the preovulatory discharge of LH.  

The largest group of cells was seen in the caudal magnocellular nucleus and medially on the dorsal and ventral aspects of the ventral premammillary nucleus.  

Bipolar concentric stimulating electrodes were implanted in the bilateral VMH or dorsal premammillary nucleus and the jugular vein was cannulated for blood sampling one week prior to the experiments. At the same time lesions of the anterior periventricular nucleus or dorsal premammillary nucleus were performed with an anodal current. On the other hand, the VMH stimulation completely failed to raise plasma GH levels in rats with dorsal premammillary nucleus lesions either during or after VMH stimulation. Although lesions of the dorsal premammillary nucleus blocked the delayed VMH-induced rise, stimulation of the dorsal premammillary nucleus itself caused no change in the plasma GH level..  

Mammillary body lesions, including large parts of the ventral and dorsal premammillary nucleus, the caudal part of the arcuate nucleus, the medial mammillary nucleus, the posterior mammillary nucleus, the supramammillary peduncle and closely surrounding areas, led to a marked increase in offensive behaviour.  

TRH or DN-1417 given into the posterior hypothalamic regions including the dorsal premammillary nucleus, lateral hypothalamic area and posterior nucleus of hypothalamus had a significant pentobarbital sleep shortening action in low doses.  

Neurons that concentrated radioactivity in their nuclei were located in widespread areas of the brain, which included the medial and suprachiasmatic preoptic nuclei, bed nucleus of the stria terminalis, lateral septal nucleus, anterior hypothalamic area, ventromedial, arcuate, dorsomedial, and paraventricular hypothalamic nuclei, ventral premammillary nucleus, and medial, cortical, basal accessory, and lateral amygdaloid nuclei.  

Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly.  

The greatest concentrations of neurons that project to the dorsal mesencephalon were found in the ventromedial nucleus, particularly the anterior and ventrolateral subdivisions, in the dorsal premammillary nucleus, and in the zona incerta.  

Projections from M to non-vomeronasal areas terminate in the medial preoptic area-anterior hypothalamic junction, ventromedial nucleus of the hypothalamus, ventral premammillary nucleus and possibly in the ventral subiculum.  

However, in the paraventricular nucleus (PV) and dorsal premammillary nucleus (PMD), marked decrease in TRH concentrations were observed with this stress.  

Vagal involvement is concluded from studies with atropine, which demonstrated total inhibition of the usual 2-DG depression of body temperature by administration to the ventral premammillary nucleus (PMV), a site that is normally extremely sensitive to this analog of glucose.  

Mean nadir Tre decreased 1.5 degrees C 1 h after, was significantly depressed 3.5 h after, and returned to basal values 4 h after administration of 2-DG into the ventral premammillary nucleus (PMV).  

Thus, we found large amounts of perikaryal enkephalin immunoreactivity in the lateral septal nucleus, bed nucleus of the stria terminalis, the preoptic nuclei, the ventral premammillary nucleus, prelateral mammillary nucleus, the medial mammillary nucleus, paraventricular nucleus, the periventricular, ventromedial, dorsomedial and posterior nuclei of the hypothalamus, the arcuate nucleus, and the ventral nucleus of the lateral geniculate body.  

The ascending components of the MFB originate in: (1) the medial preoptic nucleus, (2) the nucleus periventricularis stellatocellularis and rotundocellularis, (3) the posterior hypothalamic nucleus, (4) the parafascicular nucleus, (5) the ventral premammillary nucleus, (6) the substantia grisea periventricularis, (7) the lateral habenular nucleus, (8) the VM and DM, (9) the paratenial nucleus, (10) the AM and (11) the arcuate nucleus..  

There was also a striking association of autoradiographic grains with certain hypothalamic nuclear, i.e., the dorsal premammillary nucleus, the prelateral mammillary nucleus and the lateral mammillary nucleus.  

Immunoreactive perikarya were present in a continuum from the septal-preoptic region anteriorly to the premammillary nucleus posteriorly.  

In Man they form four main groups localized in the medio basal hypothalamus (infundibular nucleus, post-infundibular eminence, premammillary nucleus), the preopticoterminal area, the septum (and pericommissural area), the retromammillary area and the rostral mesencephalon.  

Other locations with labeled cells were the lateral septal nucleus and nucleus accumbens septi, the periventricular preoptic nucleus, anterior hypothalamic nucleus, nucleus supraopticus diffusus, posterior hypothalamic nucleus, and premammillary nucleus.  

This structure is located dorsal to the ventromedial hypothalamic nucleus (VMN) to the plane of the dorsal premammillary nucleus.  


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