Medial Parvocellular Paraventricular Nucleus Research Articles

Contribution of the ventral subiculum to inhibitory regulation of the hypothalamo-pituitary-adrenocortical axis.

Anatomical studies indicate that the ventral subiculum is in a prime position to mediate hippocampal inhibition of the hypothalamo-pituitary-adrenocortical (HPA) axis. The present study evaluated this hypothesis by assessing HPA function following ibotenic acid lesion of the ventral subiculum region. Rats with lesions of the ventral subiculum (vSUB) or ventral hippocampus (vHIPPO) did not show changes in basal corticosterone (CORT) secretion at either circadian peak or nadir time points when compared to sham-lesion rats (SHAM) or unoperated controls. However, rats with vSUB lesions exhibited a prolonged glucocorticoid stress response relative to all other groups. Baseline CRH mRNA levels were significantly increased in the medial parvocellular paraventricular nucleus (PVN) of the vSUB group relative to controls. CRH mRNA differences were particularly pronounced at caudal levels of the nucleus, suggesting topographic organization of vSUB interactions with PVN neurons. Notably, the vHIPPO group, which received large lesions of ventral CA1, CA3 and dentate gyrus without significant subicular damage, showed no change in stress-induced CORT secretion, suggesting that the ventral subiculum proper is principally responsible for ventral hippocampal actions on the HPA stress response. No differences in medial parvocellular PVN AVP mRNA expression were seen in either the vSUB or vHIPPO groups. The results indicate a specific inhibitory action of the ventral subiculum on HPA activation. The increase in CRH biosynthesis and stress-induced CORT secretion in the absence of changes in baseline CORT secretion or AVP mRNA expression suggests that the inhibitory actions of ventral subicular neurons affect the response capacity of the HPA axis.

Involvement of the bed nucleus of the stria terminalis in tonic regulation of paraventricular hypothalamic CRH and AVP mRNA expression.

The bed nucleus of the stria terminalis (BNST) occupies a central position in pathways regulating hypothalamo-pituitary-adrenocortical (HPA) stress regulation. The potential role of the BNST in tonic neural control of HPA function was assessed by examining effects of selective BNST lesions on expression of ACTH secretagogues in HPA-integrative neurons of the medial parvocellular paraventricular nucleus. Anterior BNST lesions (ABN) involved major portions of the anteromedial, anterolateral, ventromedial, ventrolateral, dorsolateral and juxtacapsular subnuclei. These lesions resulted in significant (30%) decreases in corticotropin-releasing hormone (CRH) mRNA expression across the rostrocaudal extent of the medial parvocellular PVN, with no accompanying changes in basal arginine vasopressin (AVP) mRNA levels. Posterior BNST (PBN) lesions involved large but subtotal damage to the posterior intermediate, posterior medial, posterior lateral and preoptic subnuclei; these lesions resulted in small but significant changes in CRH mRNA and slight increases in number of AVP mRNA-producing parvocellular neurons. PBN effects on CRH mRNA expression were most pronounced at the caudal extent of the medial parvocellular zone, suggesting a topographic input from the posterior BNST to the PVN that is only partially compromised by PBN lesions. Analysis of individual cases revealed a correlation between damage of the anterolateral BNST and decreased CRH mRNA levels, and damage of the posterior intermediate and/or posterior medial BNST and increased CRH mRNA levels. The results suggest differential BNST input into HPA regulation, perhaps reflecting the diversity of limbic input into the BNST region.

C-Fos expression in hypothalamic neurosecretory and brainstem catecholamine cells following noxious somatic stimuli

Noxious somatic stimuli elicit vasopressin secretion, an effect thought to result from activation of a facilitatory input from Al catecholamine cells of the medulla oblongata. To better characterize the Al cell response and effects on other neuroendocrine Al projection targets, particularly within the paraventricular nucleus, we have now mapped c-fos expression in neurochemically identified catecholamine and neurosecretory cells following a noxious somatic stimulus. Unilateral hind paw pinch significantly increased c-fos expression in contralateral Al cells whereas other brainstem catecholamine cell groups were unaffected. Expression of c-fos was also increased in the supraoptic nucleus, this effect being more pronounced for vasopressin than oxytocin neurosecretory cells and, as with Al cells, primarily on the side contralateral to the stimulated paw. In contrast, the increase in the paraventricular nucleus was greater in oxytocin rather than in vasopressin cells. Additionally there was a significant rise in c-fos expression in medial parvocellular paraventricular nucleus cells of noxiously stimulated animals. Notably, the majority of tuberoinfundibular corticotropin-releasing factor cells are located in this medial parvocellular zone. These results are consistent with and expand on those previously reported from electrophysiological and anatomical studies. The finding of differing neurosecretory cell responses between supraoptic and paraventricular nuclei has interesting implications with regard to the afferent control of neurosecretory cell activity. For example, the substantially greater activation of supraoptic versus paraventricular nucleus vasopressin cells, despite being innervated by the same medullary noradrenergic cell group, raises the possibility of a differential input or differences in responsiveness. Furthermore, the activation of paraventricular nucleus parvocellular cells is consistent with suggestions that the Al cell group provides an excitatory input to this population.

Localization of C-type natriuretic peptide mRNA in rat hypothalamus.

Central or peripheral administration of C-type natriuretic peptide (CNP) affects numerous neuroendocrine systems, including the hypothalamo-pituitary-gonadal, hypothalamo-pituitary-adrenocortical and hypothalamo-neurohypophysial axes. The present report characterizes the distribution of CNP mRNA in hypothalamus, providing the first definition of CNP-containing neuroendocrine circuits. In situ hybridization histochemical analysis revealed high expression of CNP mRNA in the anteroventral periventricular nucleus (AVPv) and in hypothalamic arcuate nucleus (ARC). Hybridization signals of significantly lower intensity were seen in the medial, median and periventricular preoptic area, the supraoptic, dorsomedial, ventral premammillary and lateral mammillary nuclei and in the posterior hypothalamic area. A few scattered CNP mRNA containing cells were visualized in the medial parvocellular paraventricular nucleus, posterior magnocellular paraventricular nucleus and lateral hypothalamic area. In the AVPv and ARC the pattern of CNP mRNA distribution paralleled that of ANP mRNA. The results indicate a distribution of CNP mRNA associated with key neuroendocrine systems, and underscores the potential importance of this novel natriuretic peptide in neuroendocrine regulation.

Localization of C-type natriuretic peptide mRNA in rat hypothalamus

Central or peripheral administration of C-type natriuretic peptide (CNP) affects numerous neuroendocrine systems, including the hypothalamo-pituitary-gonadal, hypothalamo-pituitary-adrenocortical and hypothalamo-neurohypophysial axes. The present report characterizes the distribution of CNP mRNA in hypothalamus, providing the first definition of CNP-containing neuroendocrine circuits. In situ hybridization histochemical analysis revealed high expression of CNP mRNA in the anteroventral periventricular nucleus (AVPv) and in hypothalamic arcuate nucleus (ARC). Hybridization signals of significantly lower intensity were seen in the medial, median and periventricular preoptic area, the supraoptic, dorsomedial, ventral premammillary and lateral mammillary nuclei and in the posterior hypothalamic area. A few scattered CNP mRNA containing cells were visualized in the medial parvocellular paraventricular nucleus, posterior magnocellular paraventricular nucleus and lateral hypothalamic area. In the AVPv and ARC the pattern of CNP mRNA distribution paralleled that of ANP mRNA. The results indicate a distribution of CNP mRNA associated with key neuroendocrine systems, and underscores the potential importance of this novel natriuretic peptide in neuroendocrine regulation.

Selective forebrain fiber tract lesions implicate ventral hippocampal structures in tonic regulation of paraventricular nucleus corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression

The hippocampus appears to be involved in tonic regulation of the hypothalamo-pituitary-adrenocortical axis via interactions with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP)-containing neurons of the hypothalamic paraventricular nucleus (PVN). To further investigate the anatomical basis of such interactions, lesions were made to forebrain fiber tracts in position to communicate inhibitory information from the hippocampus to the PVN. Total fimbria-fornix transections (TFF) and lateral fimbria-fornix lesions (LFF) both significantly increased CRH mRNA levels in the medial parvocellular PVN, as assayed by semi-quantitative in situ hybridization histochemistry. Medial fimbria-fornix lesions or section of the medial corticohypothalamic tracts (MCHT) did not influence CRH mRNA levels. The LFF group showed increases in both AVP mRNA and ACTH secretion, whereas no other lesion was effective in this regard. The results suggest: (1) hippocampal efferents confering tonic inhibition of the HPA axis probably originate in regions contributing to the lateral extent of the fornix, representing structures in the ventral subiculum and ventral extent of CA1: (2) projections from the hippocampus to the medial basal hypothalamus (travelling in the MCHT) are unlikely to affect HPA function: (3) hippocampus may influence the PVN CRH/AVP neuron at multiple levels, in that LFF and TFF lesions have differential effects on PVN AVP mRNA levels and ACTH secretion.

Activity of oxytocinergic neurons in the paraventricular nucleus mirrors the periodicity of the endogenous stimulatory rhythm regulating prolactin secretion.

PRL secretion is regulated by an endogenous stimulatory rhythm of PRL-releasing factors within the hypothalamus. The endogenous rhythm has a bimodal periodicity with a nocturnal component which peaks at approximately 0300 h and a diurnal component that peaks at approximately 1700 h. Several PRL-releasing factors are known to be involved in this rhythm. Among these are oxytocin (OT), vasoactive intestinal peptide, and serotonin. We have proposed that OT is the neurohormone that stimulates PRL release from the lactotroph. In this study, we examined the activity of OTergic neurons in the paraventricular nucleus using the expression of the protooncogene c-fos (Fos) as a marker of neuronal activity. Ovariectomized rats were killed at either 0300, 1200, or 1700 h and brains quickly fixed by perfusion with 2.5% acrolein in 4% paraformaldehyde. Brains were blocked and processed for OT/Fos immunohistochemistry. Rats killed at 0300 and 1700 h had significantly greater proportion of Fos expressing OTergic neurons than control rats (1200 h). Percent of Fos-positive OTergic neurons were 2- and 1.5-fold greater at 0300 and 1700 h than 1200 h, respectively. The majority of these neurons were located in the medial parvocellular paraventricular nucleus and periventricular area. In another experiment, groups of OVX rats were killed every 2 h over a 24-h period and OT extracted from their anterior and posterior pituitaries. OT was present in the anterior pituitary in a bimodal rhythm. OT concentrations were greatest at approximately 0400 h and slowly declined to baseline by 1000 h. Another peak of OT was present in the anterior pituitary at approximately 2000 h and quickly declined to baseline by 2400 h. This rhythm of OT was not reflected in either the posterior pituitary or trunk blood. These data suggest that activity of a specific population of OTergic neurons of the paraventricular nucleus is rhythmic. The periodicity of these neurons mirrors that of the endogenous stimulatory rhythm. Furthermore, the anatomical location of these neurons suggests that they may project to the median eminence. Indeed, this heightened activity is reflected in a bimodal rhythm of OT in the anterior pituitary. Taken together, the data presented here provide compelling support for the role of OT as the neurohormone in the mechanism of the endogenous stimulatory rhythm.

Rapid changes in the content of proenkephalin A and corticotrophin releasing hormone mRNAs in the paraventricular nucleus during morphine withdrawal in urethane-anaesthetized rats

Quantitative in situ hybridization was used to measure corticotrophin-releasing hormone (CRH) and proenkephalin A mRNA in the medial parvocellular paraventricular nucleus (PVN) 4 h after test procedures. Urethane anaesthesia alone resulted in a significant increase in both CRH and proenkephalin transcripts. The additional stimulus of i.p. hypertonic saline, however, resulted in a further significant increase in both mRNA species. Female rats were given intracerebroventricular (i.c.v.) infusion for 5 days of either morphine sulphate to induce tolerance and dependence, or vehicle, via a subcutaneous osmotic minipump implanted under ether anaesthesia. The rats were then anaesthetized with urethane, fitted with an intravenous cannula for injections and 65 min later either naloxone (5 mg/kg) or vehicle was injected. Naloxone alone in the i.c.v. vehicle rats had no effect on CRH or proenkephalin A mRNA. In i.c.v. morphine-infused rats proenkephalin A mRNA in the PVN was significantly less than in controls. Naloxone given to i.c.v. morphine-infused rats resulted in a doubling of hybridization to proenkephalin mRNA in the PVN which was significantly greater than that seen in the i.c.v. vehicle group. CRH mRNA in the PVN was not altered either by naloxone in control rats, or by chronic i.c.v. morphine infusion. By contrast, naloxone did increase CRH mRNA by ca. 40% in morphine-infused rats. The results show that stress-induced increases in CRH and enkephalin mRNAs in the PVN do not require conscious appreciation of the stress. Together with previous studies showing no significant change in ACTH or CRH(1–41) secretion in morphine-dependent rats given naloxone under urethane anaesthesia, the results indicate that increased gene expression need not be closely coupled to peptide release.

Chronic electroconvulsive shock treatment elicits up-regulation of CRF and AVP mRNA in select populations of neuroendocrine neurons

The effects of repeated electroconvulsive seizures (ECS) on expression of mRNAs coding for corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical (HPA) axis and hypothalamo-neurohypophysial system (HNS) were assessed via semi-quantitative in situ hybridization histochemical analysis. Measures of mRNA content were accompanied by measurement of peptide- and hormone-expression in the relevant neuroendocrine systems. Following 7 daily ECS treatments, CRF mRNA was significantly increased in the medial parvocellular paraventricular nucleus (PVN) of treated rats relative to controls. CRF peptide content of whole PVN homogenates was decreased to 50% of control levels. Changes in CRF message and peptide levels were accompanied by increases in pituitary ACTH content and by elevated plasma corticosterone, suggesting ECS elicits long-term up-regulation of the HPA axis. AVP mRNA in the medial parvocellular PVN, which is known to up-regulate in response to HPA challenge by adrenalectomy, was not increased by ECS. Chronic ECS causes a clear up-regulation of HNS neurons of the supraoptic nucleus, characterized by increased AVP mRNA content, decreased AVP peptide content, and depletion of neurohypophysial AVP. However, no changes were observed in magnocellular vasopressinergic neurons of the PVN, indicating that magnocellular SON and PVN neurons respond differentially to stimulation by ECS. The data indicate that ECS is a potent stimulus for activation of select components of both the HPA axis and the HNS. As such, ECS provides a useful tool for examining mechanism underlying neuroendocrine processes.

Direct Projections from the Central Amygdaloid Nucleus to the Hypothalamic Paraventricular Nucleus: Possible Role in Stress-Induced Adrenocorticotropin Release

The amygdala, particularly the central amygdaloid nucleus, is important for the expression of adrenocorticotropin and corticosterone responses during stress. The aim of the present study was to determine if the central amygdaloid nucleus directly innervated the hypothalamic paraventricular nucleus. To accomplish this aim, the Phaseolus vulgaris leucoagglutinin lectin anterograde tracing method was used. Injections of the tracer into the medial central amygdaloid nucleus resulted in axonal and terminal labeling within the medial and lateral parvocellular parts of the caudal paraventricular nucleus. A dense patch of labeling was observed within the lateral wing of the lateral part of the parvocellular paraventricular nucleus. Only a few labeled axons were observed within the paraventricular nucleus of animals that had lectin injections localized to the lateral part of the central nucleus. Tracer injections localized to the medial amygdaloid nucleus resulted in axonal and terminal labeling primarily within the anterior parvocellular and periventricular regions of the paraventricular hypothalamic nucleus. Sparse to moderate axonal and terminal labeling was observed within the magnocellular parts of the paraventricular nucleus in animals that had injections of tracer into either the medial central nucleus or the medial nucleus. No labeling was observed within the paraventricular nucleus of animals that had injections of lectin within other amygdaloid nuclei or adjacent regions of the striatum. The results demonstrated a topographically organized projection from the amygdala to the hypothalamic paraventricular nucleus. The central nucleus mainly innervates the caudal lateral and medial parvocellular paraventricular nucleus. The medial nucleus innervates the rostral parvocellular parts of the paraventricular nucleus. These pathways could form the anatomical substrates of amygdaloid modulation of neuroendocrine responses to stressors.

Distribution of catecholamine neurons in the hypothalamus and preoptic region of mouse.

The distribution and morphology of cells containing tyrosine hydroxylase (TH) were mapped by using the immunoperoxidase technique in the hypothalamus and preoptic area in two strains of mouse, CBA/J and BALB/cJ. On the basis of rostral-caudal contiguities between cell aggregates, hypothalamic preoptic neurons were subdivided into three arbitrary groups: (1) dorsal, (2) intermediate, and (3) ventral. New or more prominent collections of TH cells were observed, and in some regions, cells were more complexly organized than originally described. In the dorsal group, a rostral collection of small ovoid cells, previously not described, were located in the anterior preoptic nucleus (APN) of Loo ('31) and extended rostrally and ventrally into the preoptic periventricular gray. The next constituent occupied the paraventricular nucleus (PVN), and was composed of two classes of cells: (1) a small ovoid cell within anterior and medial parvocellular PVN in contiguity rostrally with a similar cell in APN and (2) a larger, angular cell within and adjacent to the lateral PVN in contiguity caudally with cells in the zona incerta (ZI). Further caudally, a larger and more pleomorphic collection of TH neurons was localized in the medial ZI, particularly at midtuberal levels. These cells were not scattered, as previously reported, but were differentiated into two clear-cut densities, a larger medial island and a more elongated lateral island. Cells of ZI, both large and small, extended caudally into the dorsal hypothalamic and subparafascicular nuclei and periventricular gray. In contrast to previous descriptions, no cells were seen in the nucleus reuniens. In the intermediate group, the most rostral constituent occupied the preoptic periventricular gray, extended as far as the lamina terminalis, and merged dorsocaudally with cells in APN. While the variably shaped cells of the hypothalamic periventricular gray (PVG) were still present in the retrochiasmatic region, a striking absence of these cells was noted at midtuberal levels between the dorsomedial and arcuate hypothalamic nuclei. At this level, a new group of small-round TH cells, resembling those of the arcuate nucleus, was identified in the dorsomedial hypothalamic nucleus (DMN). At caudal tuberal levels, similar neurons were found in the posterior hypothalamic nucleus (PH). These neurons overflowed medially into the PVG and caudoventrally into the arcuate nucleus. In the ventral group, the most rostral constituent, composed of both small and ovoid cells in the retrochiasmatic area, appeared to represent the rostral commissural portion of the arcuate nucleus (Arc).(ABSTRACT TRUNCATED AT 400 WORDS)

The magnocellular and parvocellular paraventricular nucleus of rat: Intrinsic organization

The magnocellular and paravocellular regions of the rat hypothalamic paraventricular nucleus (PVN) were examined in several hundred brains. Converging qualitative and quantitative anatomical methods, including Golgi impregnations, Nissl stains, silver stains, and immunocytochemistry were used to study the intrinsic organization of the PVN with light, scanning, and transmission electron microscopy. A computer-assisted quantitative analysis of dendritic branching patterns was used to examine total dendritic length, center of mass, orientation of dendritic tree, and several other parameters of dendritic organization and revealed statistically significant differences between cells in the lateral and posterolateral magnocellular and medial parvocellular areas of PVN. Electron microscopy, Golgi impregnation, and neurophysin immunohistochemistry showed that dendrites of posterolateral cells were generally oriented perpendicular to the third ventricle; dendrites of cells in the lateral PVN usually projected medially from the perikaryon. Cells in the medial zone of PVN had dendritic trees which often paralleled the third ventricle. Large numbers of axons entered and left PVN ventrally near the midline and laterally in the area of the posterolateral PVN; axons generally were oriented parallel to the mean major axis of dendritic trees in these areas. Ultrastructural examination of serial thin sections showed a peculiar astroglia multiple lamellar isolation of axodendritic synaptic contacts. Intrinsic axons commonly arose from parvocellular but not from magnocellular neurons and contacted dendrites of both medial parvocellular and more lateral magnocellular neurons. Synapses were found on shafts and spines of dendrites, on perikarya and somatic appendages, and invaginated into the soma. Both dendrites axons with large neurosecretory vesicles and immunostained with neurophysin antiserum were found postsynaptic to other axons. Presynaptic neurosecretory axons were not found within the PVN. A semiquantitative analysis of catecholamine axons identified with the glyoxylic acid method and fibers immunoreactive with ACTH and Substance P antisera indicated that the parvocellular region of PVN received ggreater innervation than the lateral magnocellular area; similarly, a reater density of stained fibers was found in the medial parvocellular PVN region with Golgi impregnations and silver stains. With a stereological analysis of 1-micrometer plastic sections, the parvocellular area had a significantly greater neuropil to cell volume ration, with cells accounting for 48 +/- 9% in the lateral magnocellular zone, but only for 26 +/- 7% in the parvocellular area. A quantitative analysis of vasculature from thin sections showed that the PVN had 3.3 times more blood vessels, and 3.6 times more lumen perimeter than a control area ventrolateral to PVN; an interesting finding here was that the medial parvocellular PVN had a high degree of vascularity, not significantly different from the lateral magnocellular zone...