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PubMed2004

Neural connections between the hypothalamus and the liver.

After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon-like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species-dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus-pancreas axis, the hypothalamus-adrenal axis, and the hypothalamus-pituitary axis. In the hypothalamus-pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus-adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus-pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections.

Adrenal Glands↗

PubMed1994

Hypothalamic stimulation induces vagally mediated hypocalcemia in the rat.

To elucidate hypothalamic involvement in blood calcium homeostasis, the effects of unilateral electrical stimulation (0.1 mA, 0.5 ms, 30 Hz, 60 min) of the lateral hypothalamic area (LHA), the paraventricular nucleus (PVN), and the ventromedial nucleus of the hypothalamus (VMH) on the blood concentration of ionized calcium were examined in the anesthetized rats. LHA stimulation induced a sustained decrease (0.05-0.07 mM fall) in the blood calcium level during the period of 60 to 150 min (end of the measurements) after stimulation. In contrast, PVN stimulation elicited a transient hypocalcemia (0.07 mM decrease) 60 min after stimulation. The hypocalcemic effects of LHA and PVN stimulation were eliminated by vagotomy of the gastric branches and the thyroid/parathyroid branches, respectively. VMH stimulation, using the same parameters, did not induce any significant change in blood calcium. The results suggest that the LHA and the PVN have a hypocalcemic function that is mediated, at least in part, by the vagus nerve innervating the stomach and the thyroid/parathyroid glands, respectively.

Anesthesia↗

PubMed1987

Distribution of putrescine in rat brain measured by gas chromatography-mass spectrometry.

We measured putrescine levels in minute sites of single rat brains using a sensitive, specific assay involving gas chromatography-mass spectrometry. The putrescine level was measured in 20 sites of single rat brains: three sites in the cerebral cortex, six sites in the hypothalamus, three sites in the basal ganglia, three sites in the thalamus, three sites in the limbic system, and two sites in the cerebellum. The level of putrescine was very high in the hypothalamus, high in the basal ganglia and limbic system, and low in the thalamus, cerebellum, and two of the three sites in the cerebral cortex. The highest levels were in the anterior hypothalamic area and the lateral hypothalamic area, and the lowest levels were in the vermis and the lobe of the cerebellum.

Animals↗

PubMed1986

Effects of ibotenic acid lesion in the basal forebrain on electrical self-stimulation in the middle part of the lateral hypothalamus.

The aim of the present study was to analyse the involvement of neurons located in some basal forebrain areas in electrical self-stimulation elicited from the middle part of the lateral hypothalamus. The anterior hypothalamic region was unilaterally lesioned by local injection of ibotenic acid. Ten to 20 days later 4 electrodes were implanted bilaterally, two at the lesion level and two in the middle lateral hypothalamus. A small but significant self-stimulation deficit was observed in the lesioned area, while self-stimulation on the contralateral side was normal. At the middle lateral hypothalamic level, no deficit was observed when stimulation was applied either ipsilaterally or contralaterally to the anterior lesioned side. In most cases the lesion destroyed the dorsolateral part of the lateral preoptic area, the ventral pallidum-substantia innominata complex and the lateral part of the bed nucleus of the stria terminalis. Given the fact that these regions are known to project massively to the middle lateral hypothalamic area, our data suggest that descending influences originating in the damaged regions are not involved in self-stimulation elicited from the middle hypothalamus.

Animals↗

PubMed1989

Lateral hypothalamic injection of 2-deoxy-D-glucose suppresses sympathetic activity.

To investigate the effects of glucoprivation on sympathetic nerve activity to interscapular brown adipose tissue (IBAT), 2-deoxy-D-glucose (2-DG) was injected into the third cerebral ventricle (icv), lateral hypothalamic area (LHA), and ventromedial hypothalamic nucleus (VMN) of rats. The multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically. The icv injection of high and low doses of 2-DG (5.0 and 2.5 mg/rat) suppressed sympathetic nerve activity by 76.9 and 49.8% respectively, 30 min after injection compared with preinjected base line. After the low dose of 2-DG, there was a gradual recovery, but after the high dose recovery did not occur. The unilateral microinjection of 2-DG (0.25 mg/rat) into the LHA induced a similar suppression of sympathetic nerve activity to that observed after icv injection of 10 times as much 2-DG (-25.3%). The injection of vehicle or sucrose into the LHA did not suppress sympathetic nerve activity. The microinjection into the VMN either unilaterally or bilaterally did not suppress sympathetic nerve activity to IBAT. We conclude that the LHA but not the VMH is one site of action of 2-DG. The data are consistent with the hypothesis that the brain senses glucoprivation in the LHA and reduces sympathetic drive to thermogenic tissues such as IBAT.

Adipose Tissue, Brown↗

PubMed1984

Demonstration of hypothalamo-cerebellar and cerebello-hypothalamic fibres in a prosimian primate (Galago crassicaudatus).

Hypothalamo-cerebellar and cerebello-hypothalamic fibres in the greater bushbaby (Galago crassicaudatus) have been demonstrated by means of retrograde and anterograde transport of the wheat germ agglutinin--horseradish peroxidase complex. The hypothalamo-cerebellar projection is bilateral and has its main origin in the lateral hypothalamic area. The posterior and dorsal hypothalamic areas and the lateral mammillary, tuberomammillary and periventricular nuclei also project to cerebellum. Cerebello-hypothalamic fibres are crossed and terminate in the dorsal, posterior and lateral hypothalamic areas. The hypothalamo-cerebellar and cerebello-hypothalamic projections appear to be in part reciprocal. The results are discussed with reference to our findings in other species, and some comments are made concerning the possible circuits involved in cerebellar regulation of non-somatic responses.

Animals↗

PubMed2005

Activation of lateral hypothalamic neurons stimulates brown adipose tissue thermogenesis.

The lateral hypothalamic area, containing orexin neurons, is involved in several aspects of autonomic regulation, including thermoregulation and energy expenditure. To determine if activation of lateral hypothalamic area neurons influences sympathetically-regulated thermogenesis in brown adipose tissue, we microinjected bicuculline (120 pmol, 60 nl, unilateral) into the lateral hypothalamic area in urethane/chloralose-anesthetized, artificially-ventilated rats. Disinhibition of neurons in lateral hypothalamic area evoked a significant increase (+1309%) in brown adipose tissue sympathetic nerve activity accompanied by parallel increases in brown adipose tissue temperature (+2.0 degrees C), in expired CO2 (+0.6%), in heart rate (+88 bpm) and in mean arterial pressure (+11 mm Hg). Subsequent microinjections of glycine (30 nmol, 60 nl) to inhibit local neurons in raphe pallidus or in dorsomedial hypothalamus or of glutamate receptor antagonists into dorsomedial hypothalamus promptly reversed the increases in brown adipose tissue sympathetic nerve activity, brown adipose tissue temperature and heart rate evoked by disinhibition of neurons in lateral hypothalamic area. We conclude that neurons in the lateral hypothalamic area can influence brown adipose tissue sympathetic nerve activity, brown adipose tissue thermogenesis and heart rate through pathways that are dependent on the activation of neurons in dorsomedial hypothalamus and raphe pallidus.

2-Amino-5-phosphonovalerate↗

PubMed1992

Effects of cholecystokinin on sympathetic activity to interscapular brown adipose tissue.

The effects of injecting cholecystokinin (CCK) into the third ventricle or into selected hypothalamic sites on electrical firing rate of sympathetic nerves to interscapular brown fat (IBAT) has been investigated in anesthetized rats. The hypothesis for these experiments was that there was a reciprocal relationship between sympathetic activity and food intake. Since CCK reduces food intake we predicted that CCK would stimulate sympathetic activity to IBAT. Following the injection of CCK into the third ventricle there was an increase in firing rate of sympathetic nerves to IBAT. When the peptide was injected into either the ventromedial hypothalamic nucleus (VMH) or lateral hypothalamic area (LHA), there was likewise an increase in sympathetic firing rate. The injection of CCK into the paraventricular nucleus produced a small decrease in sympathetic firing rate. In contrast, no effect was seen following injection of CCK into the preoptic area or dorsomedial hypothalamic nucleus. Thus, the VMH or LHA appear to be the principal hypothalamic areas mediating the stimulation of sympathetic activity to IBAT which is observed following the third ventricular injection of CCK. These studies support the hypothesis of a reciprocal relationship between the effects of CCK on the thermogenic component of the sympathetic nervous system and food intake and identify the VMH and LHA as the primary sites for this effect.

Adipose Tissue, Brown↗

PubMed1990

A neuronal projection from the lateral geniculate nucleus to the lateral hypothalamus of the rat demonstrated with Phaseolus vulgaris leucoagglutinin tracing.

Iontophoretic injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L), were placed in different portions of the rat lateral geniculate nucleus, and the tracer was localized by immunohistochemistry. The efferent projections of the lateral geniculate to limbic areas were analysed with special reference to projections of the lateral hypothalamic area. Only in animals, in which neurons in the intergeniculate leaflet were labeled were PHA-L-immunoreactive axons in the lateral hypothalamic area observed. The nerve fibers were mostly located in the ventral and anterior parts of the lateral hypothalamic area. This tracing study suggests that the optic system probably mediating information about the photoperiod influences not only the suprachiasmatic nucleus, but also the lateral hypothalamic area.

Animals↗

PubMed1993

Hypothalamic involvement in stress-induced hypocalcemia in rats.

Although hormonal regulation of blood calcium homeostasis has been intensively investigated in the peripheral organs, the involvement of the central nervous system in calcium regulation is still poorly understood. In the present study, we found that (1) bilateral lesions of the ventromedial nucleus of the hypothalamus (VMH), but not those of the paraventricular hypothalamic nucleus or the lateral hypothalamic area, eliminated immobilization (IMB)-induced hypocalcemia, and (2) electrical stimulation of the VMH decreased the blood calcium level. The results suggest that the VMH has a hypocalcemic function and plays a role in IMB-induced hypocalcemia.

Animals↗

PubMed2005

Neuropeptide Y content in the hypothalamic paraventricular nucleus responds to fasting and refeeding in broiler chickens.

To examine the neural mechanism by which hypothalamic neuropeptide Y (NPY) regulates energy homeostasis and feeding behavior in commercial broilers, we measured NPY content in several hypothalamic regions of birds that were fasted and then refed. After fasting for 48 and 72 h, body weight significantly decreased, and food intake significantly increased during the subsequent refeeding. The lost body weight was not restored to ad libitum feeding levels even after 3 days of refeeding. Plasma glucose concentration and body fat content significantly decreased and plasma non-esterified fatty acid (NEFA) concentration significantly increased after 48- and 72-h fasting. Refeeding for 24 h restored plasma metabolites and body fat content to pre-fasting levels. NPY content in the paraventricular nucleus (PVN) and infundibular nucleus significantly increased during fasting, and NPY content of the PVN was restored to pre-fasting levels after 24-h refeeding. However, there was no significant change in the NPY content of the lateral hypothalamic area during fasting or refeeding. The present results of changes in the hypothalamic NPY content during fasting and refeeding support the hypothesis that NPY plays a central role in regulation of energy homeostasis, with especially important effect on feeding behavior and body weight in broiler chickens.

Adipose Tissue↗

PubMed1995

Hypothalamus regulates calcium metabolism in rats.

Hypothalamic mechanisms of blood calcium homeostasis and their functional heterogeneity were investigated in rats. Electrical and chemical stimulation of the lateral hypothalamic area (LHA), the paraventricular nucleus (PVN) and the ventromedial nucleus of the hypothalamus (VMH) induced hypocalcemia. The hypocalcemic effect of PVN stimulation was suppressed by vagotomy of the thyroid/parathyroid branches, while that of LHA and VMH stimulation was eliminated by gastric vagotomy. Immobilization (IMB) stress elicited hypocalcemia through VMH-gastric vagal activation. Both IMB- and LHA stimulation-induced hypocalcemia was antagonized by muscarinic antagonist and histamine H2 blocker. The former was also blocked by alpha-blocker and gastrin release inhibitor, while the latter was antagonized by an beta-blocker. The results suggest that hypothalamic nuclei are involved in regulation of blood calcium homeostasis via the gastric or thyroid/parathyroid vagus. Muscarinic, histamine H2, adrenergic and gastrin receptors mediate the hypocalcemic effect of the hypothalamo-vagal activation depending on behavioral conditions and receptor subtypes.

Animals↗

PubMed1993

Sympathetic nerve activity after discrete hypothalamic injections of L-glutamate.

In these experiments L-glutamate, an amino acid which stimulates neuronal discharge, was microinjected into several hypothalamic nuclei and the resultant changes in electrical firing rate of sympathetic nerves innervating interscapular brown adipose tissue (IBAT) were measured. Three patterns of response were seen. A single large stimulatory response was seen when L-glutamate was microinjected into the ventromedial hypothalamus (VMH). Microinjection of L-glutamate into the paraventricular nucleus (PVN) produced a predominantly stimulatory response which was of smaller magnitude than the VMN. However in three animals L-glutamate in the PVN decreased firing rate and in one animal a biphasic response was observed. The second pattern was a decrease in sympathetic activity to IBAT which was the predominant pattern following injection of L-glutamate into the dorsomedial hypothalamus (DMH). However, a biphasic pattern was also observed. Injection of L-glutamate into the lateral hypothalamic area (LHA) produced 3 patterns of response; an increase, a decrease; or a biphasic response in nearly equal numbers of animals. The predominant response to L-glutamate in the preoptic area (POA) was biphasic. These data are consistent with the hypothesis that the VMH is the predominant stimulatory site for activation of the sympathetic nervous system to IBAT in the rat. The DMH and LHA appear to be the predominant inhibitory areas.

Adipose Tissue, Brown↗

PubMed1987

Study of the selectivity of the impregnation of neurons by the Golgi method.

The selectivity of the impregnation of neurons by the Golgi method was examined by comparing Nissl-stained specimens with Golgi-stained specimens in terms of the somatic orientation, cross-sectional area, and long and short axes of the soma in the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA) of 5-week-old rats. With regard to somatic orientation, we made comparisons directly between the Nissl distribution pattern and the Golgi pattern. The two distribution patterns did not differ significantly in either VMH or LHA (Smirnov test, P greater than 0.05). For somatic cross-sectional area and diameter (long and short), a mean value of every 10% of the total frequency was estimated for each histogram; the histogram was segmented into 10 percentile frequency domains, and a mean value for each domain was estimated. A linear regression was calculated between Golgi mean values and Nissl's at the same place. By use of the linear regression, all of the observed values on Nissl sections for somatic cross-sectional area and diameter were transformed into their corresponding Golgi values. The frequency distribution of these transformed Nissl values was compared with that of the actually observed Golgi values. There was a high degree of similarity between the two distribution patterns in all regions examined for long and short diameters as well as cross-sectional area of the soma (Smirnov test, P greater than 0.05). These findings suggest that the sampling of VMH and LHA neurons in the Golgi method used in the present study is similar to the corresponding sampling in Nissl preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Projections from the rhomboid nucleus of the bed nuclei of the stria terminalis: implications for cerebral hemisphere regulation of ingestive behaviors.

The basic organization of an exceptionally complex pattern of axonal projections from one distinct cell group of the bed nuclei of the stria terminalis, the rhomboid nucleus (BSTrh), was analyzed with the PHAL anterograde tract-tracing method in rats. Brain areas that receive a strong to moderate input from the BSTrh fall into nine general categories: central autonomic control network (central amygdalar nucleus, descending hypothalamic paraventricular nucleus, parasubthalamic nucleus and dorsal lateral hypothalamic area, ventrolateral periaqueductal gray, lateral parabrachial nucleus and caudal nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and salivatory nuclei), gustatory system (rostral nucleus of the solitary tract and medial parabrachial nucleus), neuroendocrine system (periventricular and paraventricular hypothalamic nuclei, hypothalamic visceromotor pattern generator network), orofaciopharyngeal motor control (rostral tip of the dorsal nucleus ambiguus, parvicellular reticular nucleus, retrorubral area, and lateral mesencephalic reticular nucleus), respiratory control (lateral nucleus of the solitary tract), locomotor or exploratory behavior control and reward prediction (nucleus accumbens, substantia innominata, and ventral tegmental area), ingestive behavior control (descending paraventricular nucleus and dorsal lateral hypothalamic area), thalamocortical feedback loops (medial-midline-intralaminar thalamus), and behavioral state control (dorsal raphé and locus coeruleus). Its pattern of axonal projections and its position in the basal telencephalon suggest that the BSTrh is part of a striatopallidal differentiation involved in modulating the expression of ingestive behaviors, although it may have other functions as well.

Animals↗

PubMed1997

Amygdalo-hypothalamic projections in the lizard Podarcis hispanica: a combined anterograde and retrograde tracing study.

The cells of origin and terminal fields of the amygdalo-hypothalamic projections in the lizard Podarcis hispanica were determined by using the anterograde and retrograde transport of the tracers, biotinylated dextran amine and horseradish peroxidase. The resulting labeling indicated that there was a small projection to the preoptic hypothalamus, that arose from the vomeronasal amygdaloid nuclei (nucleus sphericus and nucleus of the accessory olfactory tract), and an important projection to the rest of the hypothalamus, that was formed by three components: medial, lateral, and ventral. The medial projection originated mainly in the dorsal amygdaloid division (posterior dorsal ventricular ridge and lateral amygdala) and also in the centromedial amygdaloid division (medial amygdala and bed nucleus of the stria terminalis). It coursed through the stria terminalis and reached mainly the retrochiasmatic area and the ventromedial hypothalamic nucleus. The lateral projection originated in the cortical amygdaloid division (ventral anterior and ventral posterior amygdala). It coursed via the lateral amygdalofugal tract and terminated in the lateral hypothalamic area and the lateral tuberomammillary area. The ventral projection originated in the centromedial amygdaloid division (in the striato-amygdaloid transition area), coursed through the ventral peduncle of the lateral forebrain bundle, and reached the lateral posterior hypothalamic nucleus, continuing caudally to the hindbrain. Such a pattern of the amygdalo-hypothalamic projections has not been described before, and its functional implications in the transfer of multisensory information to the hypothalamus are discussed. The possible homologies with the amygdalo-hypothalamic projections in mammals and other vertebrates are also considered.

Amygdala↗

PubMed2000

Synchronized release of dopamine and serotonin in the medial and lateral hypothalamus of rats.

A positive linear correlation between dopamine and serotonin release was found in the ventromedial hypothalamus and in the lateral hypothalamic area in fasting rats and in fed rats during intermeal intervals. Dopamine release in the ventromedial hypothalamus positively correlated with dopamine and serotonin release in the lateral hypothalamic area, which occurred only during intermeal intervals and was non-significant during the meal consumption periods or during fasting. Meal size correlated significantly only with a decrease in serotonin release in the lateral hypothalamic area. The study was designed to evaluate the relationship between dopamine and serotonin release in these hypothalamic areas and their dependence on feeding status. Microdialysis was performed simultaneously via two probes, one in the ventromedial hypothalamus and the other in the contralateral lateral hypothalamic area, of freely moving male lean Zucker rats over 24h with preserved light and dark phase, either with ad libitum access to food and water, or when no food was available. Dopamine and serotonin concentrations were measured by high-performance liquid chromatography with electrochemical detection in 20-min dialysis samples. Time-series analysis was applied to determine linear correlations between monoamines and in relation to food intake. Data showed that release of dopamine and serotonin is synchronized within the ventromedial hypothalamus and lateral hypothalamic area, particularly in the dark phase and when no food was ingested. However, synchronized release of monoamines between these nuclei occurred only during intermeal intervals: the periods of satiety. These findings suggest a tight relationship between dopaminergic and serotonergic systems of the lateral hypothalamic area and ventromedial hypothalamus, which is influenced by the feeding state and which may be involved in maintaining the balance within and between the centers of the parasympathetic and sympathetic nervous systems. The data also illustate that food intake is coupled unequivocally to the release of dopamine and serotonin in the hypothalamus, suggesting it as a mechanism of activation of postsynaptic neurons associated with new metabolic status.

Animals↗

PubMedDate not supplied

[The neuronal reactions of the emotional areas of the hippocampus in emotional exposures of different characters].

Reaction of neurons of the emotiogenous hypothalamic regions (lateral hypothalamic area (LH), hypothalamic preoptic area (HPA), ventromedial hypothalamus (VMH)) to intracranial and peripheral emotionally positive and negative stimuli were studied in rats. These responses were compared with alteration of unit activity after feeding the food-deprived animals. Some neurons responded in the same way to all the stimuli applied (non-specific reaction). Neurons with the opposite (specific) reactions to positive and negative emotional stimuli represented 21% of recorded neurons in LH, 23% of those in HPA, and 30% in VMH. Hypothalamic neurons with non-specific and specific types of reactions seem to be the elements of different activation systems. The first of them are related to non-specific activation which determines arousal level and the second ones are involved in specific, local activation which participates in the regulation of a number of types of behaviour.

Animals↗