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Long descending projections of the hypothalamus in the pigeon, Columba livia.

An autoradiographic analysis was performed on the descending projections of nucleus periventricularis magnocellularis (PVM) of the hypothalamus in the pigeon. A PVM-medullospinal pathway was observed coursing posteriorly through the lateral hypothalamus, ventrolateral midbrain tegmentum, and into the spinal lemniscus (ls) in the ventrolateral pons and medulla. In the pons, some fibers course dorsomedially from ls and terminate at the lateral border of the locus coeruleus. At medullary levels, fibers from ls sweep dorsomedially in the plexus of Horsley and project to certain regions of the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (NX). Specifically, PVM fibers project heavily into NTS subnuclei medialis superficialis, medialis ventralis, and lateralis (sulcalis) dorsalis as well as into the ventral parvocellular subnucleus of NX. Fibers in ls were traced caudally into the lateral funiculus as far as upper cervical levels of the spinal cord. Although autoradiographs of lower cervical or thoracic spinal cord sections were not available, PVM fibers do descend to thoracic spinal cord levels, as evidenced by the retrograde transport of horseradish peroxidase. In addition to the medullospinal pathway, the autoradiographs demonstrated PVM projections to septum, diencephalon, and midbrain. Labeled PVM fibers are found in the lateral septal nucleus, nucleus of the anterior pallial commisure, dorsomedial thalamic nucleus, dorsolateral anterior thalamic nucleus (pars ventralis), median eminence, medial and lateral hypothalamus, medial mammillary area, and nucleus intercollicularis and central gray of the midbrain. The projection of fibers to medullospinal regions and median eminence suggests that PVM is homologous to the mammalian paraventricular nucleus. These projections to specific subnuclei of NTS and NX denote hypothalamic control over certain autonomic functions.

Animals↗

Projections of the suprachiasmatic nucleus to stress-related areas in the rat hypothalamus: a light and electron microscopic study.

The purpose of the present study was to investigate the sites in the hypothalamus where the suprachiasmatic nucleus (SCN) may influence corticosteroid secretion. In spite of the well established, SCN-mediated, daily rhythms in adrenocorticotrophic hormone (ACTH) and corticosteroid secretion, previous studies determining the projections of the suprachiasmatic nucleus failed to illustrate direct connections with corticotrophin-releasing hormone neurons (CRH). In order to identify where in the central nervous system the SCN may influence corticosteroid secretion, areas were selected that contained SCN efferents contacting neurons involved in the stress response. To achieve this in the present study, SCN efferents were visualized by Pha-L tract-tracing, together with the neurons involved in the stress response by immunocytochemical staining for c-fos protein. The sites where these efferents contacted c-fos-positive neurons were established by light microscopic double staining and electron microscopic immunocytochemical studies. It appeared that apart from the medial parvocellular area of the paraventricular nucleus (PVN) of the hypothalamus, many more regions showed fos-positive neurons. Sites where SCN efferents contacted such neurons are limited only to areas immediately adjacent to these putative CRH neurons but are not concentrated on these neurons themselves. These areas consist of the periventricular and rostral PVN together with the dorsomedial hypothalamus: all three regions are known to project into the PVN. Therefore, it is concluded that the SCN transmits its information related to corticosteroid secretion via interneurons in and around the PVN to the CRH-containing neurons, rather than by a direct interaction with these neurons themselves.

Adrenal Cortex Hormones↗

Novel antigenic determinant expressed in neurons of the dorsolateral hypothalamus in rat and human.

Previous studies have identified a group of cells in the dorsolateral hypothalamus that project to many different areas in the CNS, such as thalamus, diagonal band of Broca, basal ganglia, cerebral cortex, hippocampus, and olfactory bulb. Their role is presently unknown, but the cells have been reported to stain for an intriguing array of putative neurotransmitter-related substances, including alpha-melanocyte-stimulating hormone (alpha MSH), melanin-concentrating hormone (MCH), human growth-hormone-releasing factor 1-37 (hGRF 1-37), corticotropin-releasing factor (CRF), metorphamide, and acetylcholine esterase. A monoclonal antibody produced in the present study, alpha C11, stains both the cell bodies of this system in hypothalamus, with a punctate pattern, and varicose fibers in the various target areas. In double-label immunocytochemical experiments in rat DLH, alpha C11 and MCH staining exactly overlaps. Concentrations of alpha MSH and MCH high enough to completely block staining with the corresponding antisera had no effect on staining with alpha C11. Similarly, CRF, hGRF 1-37, and metorphamide were unable to block alpha C11 staining. The results suggest that the antigenic epitope for alpha C11 is not contained in alpha MSH, MCH, CRF, hGRF, or metorphamide, and thus, that alpha C11 is detecting another antigen uniquely expressed in these neurons. The punctate appearance of staining in the hypothalamus and the concentration of staining in fiber varicosities suggests that the alpha C11 epitope may be involved in synaptic function.

Acetylcholinesterase↗

Tyrosine hydroxylase-synthesizing cells in the hypothalamus of prairie voles (Microtus ochrogaster): sex differences in the anteroventral periventricular preoptic area and effects of adult gonadectomy or neonatal gonadal hormones.

The vertebrate hypothalamus and surrounding region contain a large population of cells expressing tyrosine hydroxylase (TH), the rate limiting enzyme for synthesis of dopamine and other catecholamines. Some of these populations are sexually dimorphic in rats. We here examined sex differences in TH-immunoreactive populations in the forebrain of gonadally intact and gonadectomized prairie voles (Microtus ochrogaster), a species that sometimes shows unusual sexual differentiation of brain and behavior. A sex difference was found in the anteroventral periventricular preoptic area (AVPV; likely analogous to the rat rostral A14) only in gonadectomized subjects, which was due to a 50% reduction in the number of TH-immunoreactive cells after castration in males. There was no significant sex difference or effects of gonadectomy on the number of TH-immunoreactive cells in the anteroventral preoptic area (AVP), periventricular anterior hypothalamus (caudal A14), arcuate nucleus (A12), zona incerta (A13), or posterodorsal hypothalamus (A11). In a second experiment, testosterone propionate (TP; 500 microg), diethylstilbestrol (DES; 1 microg), or estradiol benzoate (EB; 30 microg) injected daily during the first week after birth each significantly reduced later TH expression in the AVPV of females by approximately 40-65% compared to oil-treated controls. Unlike rats, therefore, a sex difference in TH expression in the prairie vole AVPV is found only after removal of circulating gonadal hormones in males. Furthermore, unlike our previous findings on the generation of sex differences in extra-hypothalamic arginine-vasopressin expression in prairie voles, TH expression in the AVPV of female prairie voles can be highly masculinized by neonatal exposure to either aromatizable androgens or estrogens.

Animals↗

Rapid changes in monoamine levels following administration of corticotropin-releasing factor or corticosterone are localized in the dorsomedial hypothalamus.

Monoaminergic systems are important modulators of the neuroendocrine, autonomic, and behavioral responses to stress-related stimuli. The male roughskin newt (Taricha granulosa) was used as a model system to investigate the effects of corticotropin-releasing factor (CRF) or corticosterone administration on tissue concentrations of norepinephrine, epinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) in microdissected brain areas. Intracerebroventricular infusion of 25 or 50 ng of CRF increased locomotor activity and site-specifically increased dopamine concentrations within the dorsomedial hypothalamus 30 min after treatment when compared to vehicle-treated controls. In further studies, male newts were treated as follows: (1) no injection, no handling, (2) saline injection, or (3) 10 microg corticosterone and then placed in a novel environment. Monoamine and monoamine metabolite concentrations were similar in the unhandled and saline-injected controls 20 min after treatment. In contrast, corticosterone-injected newts had elevated concentrations of dopamine, serotonin, and 5-HIAA in the dorsomedial hypothalamus (a region that contains dopamine- and serotonin-accumulating neuronal cell bodies in representatives of all vertebrate classes) but not in several other regions studied. These site-specific neurochemical effects parallel neurochemical changes observed in the dorsomedial hypothalamic nucleus of mammals following exposure to a variety of physical and psychological stress-related stimuli. Therefore, these changes may reflect highly conserved, site-specific neurochemical responses to stress and stress-related neurochemicals in vertebrates. Given the important role of the dorsomedial hypothalamus in neuroendocrine, autonomic, and behavioral responses to stress, and a proposed role for this region in fast-feedback effects of glucocorticoids on the hypothalamo-pituitary-adrenal axis, these stress-related monoaminergic changes are likely to have important physiological or behavioral consequences.

Animals↗

Morphological aspects of the hypothalamic-hypophyseal system. VI. The tanycytes: their relation to the sexual differentiation of the hypothalamus. An enzyme-histochemical study.

Enzyme-histochemical methods were used to study the metabolic activity of specialized ependyma of the ventrolateral walls and floor of the third ventricle in young male and female rats during the "critical period" of sexual differentiation of the hypothalamus (one week after birth). Histochemical tests were conducted for glutamic dehydrogenase, lactic dehydrogenase, glucose-6-phosphate dehydrogenase, glycerophosphate dehydrogenase and NADH2-dehydrogenase. Enzyme activity was judged by cytospectrophotometry. All the data were treated statistically. It was found that the specialized ependyma of the ventrolateral wall and floor of the third ventricle (median eminence) in rats differed in their enzyme behaviour in males and females during the "critical period" of sexual differentiation of the hypothalamus. At the level of the arcuate nucleus (alpha2-tanycytes) and the medial part of the median eminence (beta2-tanycytes) the ependyma was characterized by similar indices of metabolic activity in males and females in the decisive terms of the "critical period" (days 3, 5, and 7). On day 5 metabolic activity of these cells was reduced both in the males and in the females. Prominent sexual differences in the intensity of the enzyme reactions studied were noted in the ependyma of the lateral parts of the median eminence (beta1-tanycytes) in the "critical period". On day 5 metabolic activity of beta1-tanycytes was reduced in males and increased in females. It is suggested that these differences are caused by the receptor nature of beta1 tanycytes and suggest their implication in the mechanisms of sexual differentiation of hypothalamus.

Animals↗

Maturation of the hypothalamo-neurohypophysial system. I. Localization of neurophysin, oxytocin and vasopressin in the hypothalamus and neural lobe of the developing rat brain.

Sections of the hypothalamus, median eminence and pituitary from fetal and neonatal rats were examined with the immunoperoxidase staining technique and light microscopy. Purified antisera raised against vasopressin and oxytocin, and antisera cross-reactive with rat neurophysin were used to localize these antigens in the hypothalamo-neurohypophysial system (HNS). Neurophysin was detected throughout the HNS of the 18-day fetal rat. Vasopressin was present in the hypothalamus and pituitary of the 19-day fetus, and in the median eminence of the 4-day neonate. Oxytocin was not detected in the pituitary until 1--2 days after birth, in the hypothalamus after 4 days, and in the median eminence after 8 days. During the first days after birth the supraoptic nucleus was more mature than the paraventricular nucleus. The HNS did not approach maturity until at least 7 days after birth. The relative maturity of the supraoptic nucleus compared with the paraventricular nucleus, and the detection of vasopressin before oxytocin are evidence for the one-neuron-one-hormone theory. The data do not exclude the possibility that the fetal hypothalamo-neurohypophysial system, and perhaps the fetal hormone, vasotocin, affect the initiation and course of parturition.

Animals↗

Conditioned bradycardia in the rabbit: effects of knife cuts and ibotenic acid lesions in the lateral hypothalamus.

New Zealand albino rabbits received either parasagittal or coronal knife cuts in the lateral hypothalamus (LH). Other animals received ibotenic acid lesions of LH. Pavlovian conditioning was studied in these animals and compared with that of sham operated, vehicle, or unoperated control animals. Tones served as conditioned stimuli (CSs) and periorbital electric shocks as unconditioned stimuli (USs). Coronal knife cuts that interrupted fibers passing through LH abolished the bradycardia elicited by these contingencies, as well as the cardiac component of the orienting reflex (OR), which also consisted of bradycardia. Parasagittal knife cuts medial to the temporal lobe but lateral to the major nuclei of the hypothalamus also completely abolished conditioned bradycardia, but had no effect on the OR, compared to sham and unoperated control animals. These lesions also had no effect on concomitantly occurring eyeblink conditioning. Ibotenic acid lesions of LH had no effect on conditioned bradycardia but diminished the magnitude of the cardiac OR. Control experiments suggest that the damage produced by these manipulations had no effect on either sensitivity to the CS or US and produced no general motoric difficulties. These data thus suggest that structures rostral to the hypothalamus, probably in the amygdala and/or agranular prefrontal cortex, mediate the bradycardia associated with classical conditioning contingencies, but that hypothalamic mechanisms may mediate the OR.

Animals↗

The kallikrein-kinin system in the rat hypothalamus. Immunohistochemical localization of high molecular weight kininogen and T kininogen in different neuronal systems.

High molecular weight kininogen (HKg) and T kininogen (TKg) were detected and localized by immunocytochemistry in adult rat hypothalamus. In addition, kininogens were measured by their direct radioimmunoassay (RIA) or by indirect estimation of kinins released after trypsin hydrolysis and high pressure liquid chromatography (HPLC) separation of bradykinin (BK) and T kinin. A specific HKg immunoreactivity demonstrated with antibodies directed against the light chain (LC) of HKg was colocated with SRIF in neurons of hypothalamic periventricular area (PVA) projecting to external zone (ZE) of median eminence (ME). Heavy chain (HC) immunoreactivity which could be related to HKg or to low molecular weight kininogen (LKg) was detected in some other systems: i) parvocellular neurons of suprachiasmatic (SCN) and arcuate nuclei containing SRIF, ii) magnocellular neurons (mostly oxytocinergic) of paraventricular (PVN) and supraoptic (SON) nuclei, iii) neurons of dorsomedian and lateral hypothalamic areas. TKg immunostaining was restricted to magnocellular neurons of PVN, SON, accessory nuclei (mostly vasopressinergic) and to parvocellular neurons of SCN (vasopressinergic). TKg projections are directed towards the internal zone (ZI) of ME, but very few immunoreactive terminals are detectable in neurohypophysis. TKg staining parallels with vasopressin during water deprivation, and is undetectable in homozygous Brattleboro rats. In some magnocellular neurons, TKg and HC (related to HKg or LKg) are coexpressed. TKg, was also detected in hypothalamus and cerebellum extracts by direct RIA, and BK and T kinin were identified after trypsin hydrolysis. HKg and LKg can act as precursor of BK which can play a physiological role as releasing factor, neuromodulator--neurotransmitter,--or modulator of local microcirculation in hypothalamus. The three kininogens are also potent thiolprotease inhibitors which could modulate both the maturation processes of peptidic hormones and their inactivation and catabolism.

Animals↗

Co-localization of putative vasopressin receptors and vasopressinergic neurons in rat hypothalamus.

Vasopressin and oxytocin are synthesized by neurons in the paraventricular and supraoptic nuclei of hypothalamus. Dense concentrations of vasopressin binding sites have also been localized in these nuclei. Using a vasopressin anti-idiotypic antiserum, a dual immunocytochemical labeling procedure has been employed to elucidate the distribution of putative vasopressin receptors in anatomical relation to vasopressin and oxytocin immunoreactive cells in rat brain. Putative vasopressin receptors are observed in relation to magnocellular neurons in hypothalamus that are vasopressin immunoreactive. They do not appear to be associated with parvocellular vasopressinergic cells or oxytocin immunoreactive neurons. The presence of these presumed autoreceptors would support evidence that vasopressin may autoregulate the activity of magnocellular vasopressinergic neurons in hypothalamus.

Animals↗

Microsurgery of the hypothalamus with special reference to craniopharyngioma.

After a short survey of microanatomy, microtopography, neurophysiology and neuropathophysiology of the hypothalamus the surgical approaches to the hypothalamus with special reference to the craniopharyngiomas are described in detail. Based on 100 personal cases (1954-1979) the special procedure, depending on the site and extent of the tumour and its involvement of the hypothalamus, is discussed. Primary radical excision (19 cases) with a mortality rate of 10.5% seems to be the method of choice, as late mortality recurrences and secondary operations are frequent after non-radical procedures. Modern microsurgical technique promises to achieve primary radical excision more frequently and with less risk.

Cerebral Angiography↗

A case of isolated langerhans cell histiocytosis of the hypothalamus with remission and regrowth after surgery.

We describe a new case of isolated Langerhans cell histiocytosis (LCH) of the hypothalamus. A 53-year-old female patient presented with polydipsia, headache, anorexia, and fatigue. Neurological imaging revealed a mass projecting from the hypothalamus into the third ventricle. Gross total removal of the tumor was performed. Light microscopy showed LCH, and immunohistochemical studies revealed S-100 and CD1a immunoreactivity in the Langerhans cells. Although the most common CNS site for LCH is the hypothalamus, isolated hypothalamic LCH, confirmed by biopsy, is very rare. The residual mass appeared to remit spontaneously 3.5 years after surgery, with regrowth 3 years later.

Female↗

Multiple deep-seated cavernomas in the third ventricle, hypothalamus and thalamus.

BACKGROUND: Cavernomas are rarely located in the third ventricle, hypothalamus, or thalamus. In this report, we present our experience managing a patient with three cavernomas, one each in the floor of the third ventricle, hypothalamus, and left thalamus. CASE PRESENTATION: This 62-year-old woman had had an unsteady gait and weakness of both legs for six months. Magnetic resonance imaging (MRI) revealed multiple intracranial tumours in the third ventricle, hypothalamus, and left thalamus. The third ventricle tumour was found to be a cavernoma by intra-operative endoscopic examination and then was excised via a transcortical, transventricular approach. Pathology revealed a cavernoma. The other two tumours were assumed to be cavernomas because of their MRI features. Three days after surgery, the patient developed right hemiparesis and disturbance of consciousness. Computed tomography revealed a left thalamic haemorrhage. After conservative treatment, her conscious level gradually recovered and she could walk with support seven months after surgery. INTERPRETATION: Our experience with this rare case of multiple, deep-seated cavernomas suggests that management of such patients requires specific consideration of the clinical manifestations, location, size, and previous bleeding history.

Brain Neoplasms↗

Response suppression in rats after bilateral microinjection of 5-hydroxytryptophan in lateral hypothalamus.

Studies using the 5-hydroxytryptophan (5-HTP) animal model of depression have led to the development of the hypersensitive postsynaptic serotonin receptor theory of depression. To demonstrate more clearly that the 5-HTP-induced suppression is a centrally mediated phenomenon, rats were implanted with bilateral cannulae in the lateral hypothalamus and received microinjections of D,L-5-HTP (100-500 ng) 15 min after the start of a VI operant session (milk reinforcement). Significant decreases in responding were observed that were comparable to those obtained after a systemic injection of 50 mg/kg D,L-5-HTP. Rats receiving a microinjection of 5-HTP in the posterior hypothalamus did not exhibit a behavioral effect. Rats working on shock-avoidance schedules did not demonstrate response suppression following microinjection of 5-HTP into the lateral hypothalamus, which is the same result as that following systemic 5-HTP administration. These data support the important role previously assigned to central 5-HT mechanisms in the 5-HTP animal model of depression.

5-Hydroxytryptophan↗

Spinal monoamine mediation of stimulation-produced antinociception from the lateral hypothalamus.

Stimulation-produced antinociception can be evoked from a wide variety of sites in the brain, including the lateral hypothalamus (LH). The present study, in rats lightly anesthetized with pentobarbital, examined descending inhibition of the nociceptive tail flick (TF) reflex produced by focal electrical stimulation in the LH and the neurotransmitter(s), at the level of the lumbar enlargement, mediating the inhibition. Systematic tracking studies demonstrated that stimulation in the diencephalon dorsal to the hypothalamus did not reliably inhibit the TF reflex. Inhibition of the TF reflex was produced, however, throughout the hypothalamus at intensities of stimulation typically between 50 and 200 microA. The area requiring low intensities of stimulation (50-100 microA) to inhibit the TF reflex was a diffuse region of the LH, inferior to the mammillothalamic tract and internal capsule, medial to the supraoptic decussation and including the medial forebrain bundle. Microinjections of S-glutamate (100 mM, 0.5 microliter) in the LH did not inhibit the TF reflex, suggesting that activation of fibers of passage by stimulation was responsible for inhibition of the TF reflex produced from the LH. The intrathecal administration of pharmacologic antagonists (15-30 micrograms; naloxone, methysergide, phentolamine, prazosin or yohimbine) revealed that the alpha-adrenoceptor antagonists phentolamine and yohimbine produced the greatest increases in stimulation thresholds in the LH for inhibition of the TF reflex (83.7% and 89.8%, respectively). The intrathecal administration of methysergide produced a lesser, but statistically significant 11% increase in the stimulation threshold for inhibition of the TF reflex. These results indicate that spinal alpha 2-adrenoceptors primarily mediate the descending inhibition of the TF reflex produced by electrical stimulation in the LH.

Adrenergic alpha-Antagonists↗

Gustatory preference-aversion thresholds are increased by ibotenic acid lesion of the lateral hypothalamus in the rat.

The main purpose of this study was to quantitate possible changes in the rewarding and aversive values of certain gustatory stimuli produced by bilateral ibotenic acid lesions of the lateral hypothalamus in the rat. Non-operated rats served as controls. Thirteen days after the operation, rats were placed on a water-deprivation schedule during 5 consecutive days. Rats were then given the choice of one of 5 concentrations of saccharin solution, using a two-bottle procedure. Fluid intake across concentrations generated a preference-aversion curve. The same type of procedure was used to obtain the aversion curve for increasing concentrations of quinine solution. The lesioned rats as well as the control animals showed a clear preference-aversion response to saccharin solutions and an aversive response to quinine solutions. However, the highest preference score of the lesioned rats was obtained with a saccharin concentration 3 times higher than the concentration preferred by the control rats. Moreover, unlike control rats operated animals did not show aversion to the highest concentrations of saccharin solutions. Finally in the lesioned rats the aversion threshold to quinine solutions was obtained with concentration 5 times higher than the concentration inducing aversion in the control rats. At the end of these experiments, rats used as controls were submitted, in turn, to bilateral lesion of the lateral hypothalamus. The change in the preference-aversion threshold of these rats in the saccharin choice procedure was the same as that observed with naive rats. Taken together, these results suggest that in the normal rat the palatability of certain gustatory stimuli is modulated by the intrinsic neurons of the lateral hypothalamus.

Animals↗

Many progestin receptor-containing neurons in the guinea pig ventrolateral hypothalamus contain substance P: immunocytochemical evidence.

Behavioral and neuroanatomical evidence in rats suggests that substance P may mediate hormonally induced sexual receptivity. To determine if progestin receptor-containing neurons in the guinea pig hypothalamus also contained substance P, we used a double antibody, immunocytochemical technique. Ovariectomized, adult guinea pigs were estradiol-primed for one week. Two days prior to perfusion, colchicine was infused into the lateral ventricle. Substance P-immunoreactive neurons and progestin receptor-immunoreactive neurons were found throughout the hypothalamus and caudal preoptic area. However, substance P and progestin receptor immunoreactivity occurred in the same neurons almost exclusively in the ventrolateral area of the hypothalamus, an important site in the hormonal regulation of female sexual behavior in guinea pigs. Within this area, approximately 35% of the progestin receptor-immunoreactive neurons also contained substance P immunoreactivity. These neuroanatomical data are consistent with the hypothesis that substance P may mediate some of the neural actions of progesterone.

Animals↗

Evidence for a non-genomic action of progestins on sexual receptivity in hamster ventral tegmental area but not hypothalamus.

Progestogenic stimulation of both the ventromedial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) is critical for normal receptivity in estrogen-primed hamsters. However, anatomical and biochemical studies have identified very few estrogen-induced progestin receptors in the rodent ventral midbrain. To determine whether progesterone might be working on the membrane of neurons in the VTA, progesterone 3-CMO BSA (P-3-BSA) was applied intracranially. The size of P-3-BSA makes it relatively impermeable to the cell membrane. Ovariectomized hamsters were implanted with 2 chronic cannulae, one aimed at the VMH and the other at the contralateral VTA. These animals were then estrogen-primed and tested for sexual receptivity after progesterone-containing tubes were inserted just dorsal to the VMH and P-3-BSA inserts were applied above the VTA. The following week, the hamsters were tested again with the contents of the inserts reversed. Animals with progestogenic stimulation to the VMH and P-3-BSA to the VTA were receptive yet those with P-3-BSA to the hypothalamus and progesterone to the VTA were not receptive. These data suggest that progesterone is capable of facilitating sexual receptivity within the VTA by actions on the cell membrane. The non-genomic effects in the VTA require concurrent genomic activation by progesterone within the hypothalamus.

Animals↗