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PubMed1976

Dual localization of histamine in an ascending neuronal pathway and in non-neuronal cells evidenced by lesions in the lateral hypothalamic area.

The effects of lesions placed in the lateral hypothalamic area, i.e., interrupting the MFB (as evidenced by a 65% decrease in cortical noradrenaline and serotonin) suggest a pluricompartmentation of brain histamine (HA). The existence of an ascending histaminergic system is indicated by the reductions in l-histidine decarboxylase (H.D.) activity, in [3H]histamine synthesis and in HA content, in the cortex of lesioned rats. Moreover, the decrease in H.D. activity was restricted to the regions rostral to the lesion, without modification caudally. The time-course of the alterations in H.D. activity and in HA content is compatible with a process of anterograde degeneration. In subcellular fractionation studies, the reduction in cortical HA content was found to be mainly confined to the P2 fraction, which contains the synaptosomes. Although the widespread ipsilateral distribution of HA synthesizing terminals resembles that of monoaminergic ones, the absence of reduction in H.D. activity after selective destruction of catecholaminergic and serotoninergic neurons, by 6-hydroxydopamine or 5,6-dihydroxytryptamine respectively, renders likely the existence of specific HA-containing neurons. That the release of the amine from these neurons might be related to the nerve impulse flow is suggested by the transient effects of the lesions which preceded the degenerative process (elevated endogenous HA level and slowed rate of [3H]HA synthesis). In addition, the discrepancy between the reduction in H.D. activity and in HA level after the lesions could be explained by the presence of the amine in another neuronal system and/or in non-neuronal cells, not affected by the lesion. This additional compartment is characterized by a high HA content and a low H.D. activity and could therefore be localized in mast-cells. The respective sizes of these two compartments, estimated by several methods, appear to be approximately the same.

5-Hydroxytryptophan↗

PubMed1977

Adrenergic stimulation of the lateral hypothalamic area on sodium and potassium excretion.

The effects of adrenergic stimulation of the lateral hypothalamic area on sodium and potassium excretion were studied in rats bearing implanted cannulae. When noradrenaline was injected into several points of the lateral hypothalamic area, a dose-related increase in natriuresis and kaliuresis was observed. Rats previously injected through the same cannulae with alpha (Regitine) or beta (Propranolol) blocking agents showed different natriuretic responses when injected with noradrenaline. It was observed that the normal noradrenaline-induced natriuresis was abolished by the alpha-adrenergic blockers, while beta-adrenergic blockers increased the response. Intrahypothalamic injection of Isoproterenol, and activator of the beta-adrenergic receptor, induced a decrease in natriuresis, kaliuresis and urinary volume. In contrast, injection of Metaraminol, an alpha-adrenergic agonist, caused an increase in sodium and potassium excretion and a reduction of urinary volume. Drugs blocking the destruction of noradrenaline or its reuptake by the presynaptic nerve endings potentiated 2-fold the action of 20 nmol of noradrenaline. These experiments provide good evidence for the existence of an adrenergic mechanism consisting of alpha and beta receptors which works antagonistically on the regulation of sodium and potassium excretion. The excretion on the two electrolytes is stimulated by the alpha-adrenergic system, and inhibited by the beta-adrenergic system.

Animals↗

PubMed1994

An interaction between glucose and estrogen in gastric acid secretion in the lateral hypothalamic area of female rats.

Gastric acid outputs caused by glucose injection into the lateral hypothalamic area (LHA) were examined in insulin hypoglycemia with or without estradiol-17 beta (EST) administration in bilaterally ovariectomized (OV) female rats. The basal level of acid output was higher in OV rats without EST than in OV rats with EST. When acid response was expressed as the percentage change, glucose injection into the LHA decreased acid output in a dose-dependent fashion in OV rats, while, in OV rats with EST, glucose injection into the LHA also reduced acid output without dose dependency. It was also noted that the threshold concentration of glucose that induced an acid response was lower in OV rats without EST than in OV rats with EST. These findings suggest that glucose-sensitive neurons responsible for gastric acid secretion can be modulated by estrogen at the LHA level.

Adrenalectomy↗

PubMed1995

Cerebellar interpositus nucleus modulates neuronal activity of lateral hypothalamic area.

Effects of stimulating the cerebellar interpositus nucleus (IN) on the neuronal activity of lateral hypothalamic area (LHA) were first observed in the cat. The results showed that (1) IN stimulation could elicit inhibitory, excitatory, inhibitory-excitatory and excitatory-inhibitory responses from LHA neurones, with a majority of inhibitory responses (46.9%); (2) the responsive latencies of LHA neurones to IN stimulation ranged from 5 to 45 ms, while most (83.6%) showed a short latency of < 15 ms; (3) of 67 LHA neurones which responded to the IN stimulation, 42 (62.7%) cells were identified to be glucose-sensitive neurones. These results suggest that IN may be involved in the role of LHA modulating food intake behaviour, as well as other non-somatic functions.

Animals↗

PubMed1987

The differential descending projections from the anterior, central and posterior regions of the lateral hypothalamic area: an autoradiographic study.

The descending projection sites of the anterior, central (or tuberal) and posterior regions of the lateral hypothalamic area were studied by anterograde axonal transport after local injection of tritiated amino acids. The results show that the neurons of the anterior regions project to the lateral mammillary nucleus, the ventral tegmental area, the midbrain central gray and the anterior parts of the dorsal raphe nucleus. The neurons of the central region project in the same structures and extend a projection into the dorsal tegmentum at the level of the pontine central gray, the midbrain and pontine reticular nuclei. In the ventral tegmentum region, the substantia nigra pars compacta, the interpeduncular nucleus and the anterior group of raphe nuclei were also found to be labelled. The neurons of the posterior region of the lateral hypothalamic area extend a projection to the level of the prepositus hypoglossi nucleus and to the nucleus of solitary tract. In the ventral tegmentum they project at the level of posterior group of the raphe nuclei and the inferior olivary complex.

Afferent Pathways↗

PubMed1980

Cells of origin of the descending afferents to the lateral hypothalamic area in the rat, studied with the horseradish peroxidase method.

Cells of origin of the descending afferents to the lateral hypothalamic area (LHA) were examined following iontophoretic injections of horseradish peroxidase (HRP). HRP-positive neurons were found ipsilaterally and mainly in the following structures: the infralimbic cortex (area 25), septal area including the nucleus of the diagonal band, nucleus accumbens, olfactory tubercle, medial and lateral preoptic areas, preoptic magnocellular nucleus, substantia innominata, bed nucleus of the stria terminalis and the central amygdaloid nucleus. Of these, neurons of the nucleus accumbens, olfactory tubercle, preoptic magnocellular nucleus and substantia innominata were preferentially labeled when the enzyme was deposited in the lateral part of the LHA.

Afferent Pathways↗

PubMed1998

Melanin-concentrating hormone and neuropeptide EI projections from the lateral hypothalamic area and zona incerta to the medial septal nucleus and spinal cord: a study using multiple neuronal tracers.

The projection pathways of neurons containing melanin-concentrating hormone (MCH) and neuropeptide EI (NEI), two peptides colocalized in the lateral hypothalamic area (LHA) of the rat, were mapped using the retrogradely transported fluorescent dyes, true blue (TB) and diamidino yellow (DY). TB and DY were injected into the medial septum/diagonal band complex (MS/DBC) and the thoracic level of the spinal cord (SpCd), respectively. Brains from rats receiving only one or both tracer injections were immunohistochemically stained for MCH in the spinal cord and NEI in the forebrain. In the MS/DBC, NEI-immunoreactive (-ir) fibers are concentrated in the MS and in the vertical and horizontal limbs of the DBC. In the SpCd, MCH-ir fibers are concentrated primarily in lamina X. Of the diencephalic NEI-ir neurons, 37.15% project to the MS/DBC and reside in the rostromedial zona incerta (ZIm), in the LHAt and LHAp, and in the perifornical region. Of the diencephalic MCH-ir neurons, 20.2% project to the SpCd and reside in the LHAt and LHAp. In addition, 2. 2% of the MCH-ir cells and 8.7% of the NEI-ir cells in the hypothalamus were labeled with both retrograde tracers and thus project to both the MS/DBC and SpCd. These dual projection neurons are located mainly in the LHAt and LHAp. Anterograde injections of the tracer Phaseolus vulgaris leucoagglutinin into the LHAt and ZIm corroborated our findings in the retrograde studies. Potential autonomic and behavioral roles of the NEI and MCH systems in the MS/DBC and the SpCd are discussed.

Amidines↗

PubMed1998

Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area.

Recent studies have identified several neuropeptide systems in the hypothalamus that are critical in the regulation of body weight. The lateral hypothalamic area (LHA) has long been considered essential in regulating food intake and body weight. Two neuropeptides, melanin-concentrating hormone (MCH) and the orexins (ORX), are localized in the LHA and provide diffuse innervation of the neuraxis, including monosynaptic projections to the cerebral cortex and autonomic preganglionic neurons. Therefore, MCH and ORX neurons may regulate both cognitive and autonomic aspects of food intake and body weight regulation. The arcuate nucleus also is critical in the regulation of body weight, because it contains neurons that express leptin receptors, neuropeptide Y (NPY), alpha-melanin-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP). In this study, we examined the relationships of these peptidergic systems by using dual-label immunohistochemistry or in situ hybridization in rat, mouse, and human brains. In the normal rat, mouse, and human brain, ORX and MCH neurons make up segregated populations. In addition, we found that AgRP- and NPY-immunoreactive neurons are present in the medial division of the human arcuate nucleus, whereas alpha-MSH-immunoreactive neurons are found in the lateral arcuate nucleus. In humans, AgRP projections were widespread in the hypothalamus, but they were especially dense in the paraventricular nucleus and the perifornical area. Moreover, in both rat and human, MCH and ORX neurons receive innervation from NPY-, AgRP-, and alpha-MSH-immunoreactive fibers. Projections from populations of leptin-responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and may play a critical role in the regulation of feeding behavior and body weight.

Agouti-Related Protein↗

PubMed1977

The lateral hypothalamic area. An ultrastructural analysis.

An ultrastructural analysis of the rat lateral hypothalamic area (LHA) was undertaken in order to provide an initial step in the characterization of this complex area which appears to participate in a number of important neural functions. The organization of the normal tuberal LHA was compared to the area following acute and chronic denervating lesions. In the normal animal, the principal features of the LHA are the presence of lateral hypothalamic neurons, a major sagittal pathway (the medial forebrain bundle, MFB) and the interposed neuropil richly populated by a variety of synaptic terminal types. Alterations in the synaptic organization of the LHA following rostral and caudal MFB lesions were most pronounced in animals with acute and chronic caudal lesions. A 10% reduction of synaptic terminals containing 800-1000 A diameter dense core vesicles and a 10% increase in terminals containing lucent core vesicles was observed in animals with caudal lesions while no significant redistribution of synaptic terminal types occurred with rostral lesions. The preliminary degeneration experiments indicate that identification of the numerous and diverse afferents to the LHA neuropil may be aided by this method but that a detailed and systematic ultrastructural analysis will be required to identify sources of input with certainty.

Animals↗

PubMed1993

[Effects of stimulating lateral hypothalamic area and ventromedial nucleus of hypothalamus on cerebellar cortical neuronal activity in the cat].

In pentobarbital anaesthetized cat, stimulating lateral hypothalamic area (LHA) and ventromedial nucleus (VMN) of the hypothalamus could elicit inhibitory, excitatory or inhibitory-excitatory responses of cerebellar Purkinje cells (PC) and non-Purkinje cells (NPC) in the loubles VI and VII. The majority of responses are inhibitory (80.4%) usually with a latency of 10-20 ms, or occassionaly as long as 90 ms. Usually stimulation of LHA was more effective and NPC was more responsive. The aforementioned inhibitory response could be blocked by iv. chlorpheniramine. The possible role of the hypothalamo-cerebellar activity was discussed.

Animals↗

PubMedDate not supplied

Effect of lateral hypothalamic area lesions on serotonin-containing epithelial cells in rat duodenum.

The aphagic effect of lateral hypothalamic area (LHA) lesions induced by kainic acid injection on serotonin (5HT)-containing epithelial cells in rat duodenum was studied in comparison with food deprived rats. The densities of 5HT cells were evaluated by quantitative morphometry using fluorescent histochemical longitudinal sections. The levels of 5HT/mg tissue were determined by HPLC on acid extracts of isolated villous epithelium. Body and duodenal weight losses, as well as duodenal mucosal atrophy, were comparable in the two groups of starved animals, i.e., one is food deprived and the other is lesioned animals. The numbers of 5HT cells in these starved groups were similar to those in controls so that the densities were increased. The 5HT/mg tissue in food-deprived animals was similar to that in controls but significantly higher in the LHA-lesioned group. These results are interpreted in terms of a possible central regulatory mechanism that is intact in the food-deprived animals but destroyed in the lesioned animals.

Animals↗

PubMed1983

Neural projections from nucleus accumbens to globus pallidus, substantia innominata, and lateral preoptic-lateral hypothalamic area: an anatomical and electrophysiological investigation in the rat.

The anatomical organization and electrophysiological characteristics of a projection from the nucleus accumbens to anteroventral parts of the globus pallidus and to a subpallidal region that includes the substantia innominata (SI), the lateral preoptic area (LPO), and anterior parts of the lateral hypothalamic area (LHA) were investigated in the rat. Autoradiographic experiments, with injections of 3H-proline into different sites in the nucleus accumbens and adjacent caudoputamen, indicate that the descending fibers are organized topographically along both mediolateral and dorsoventral gradients, although labeled fibers from adjacent regions of the nucleus accumbens overlap considerably in the ventral globus pallidus and subpallidal region. Injections confined to the caudoputaman only labeled fibers in the globus pallidus. Retrograde transport experiments with the marker true blue confirmed that only the nucleus accumbens projects to the subpallidal region and that the caudoputamen projects upon the glubus pallidus in a topographically organized manner. In electrophysiological recording experiments single pulse stimulation (0.1 to 0.7 mA; 0.15 msec duration) of the nucleus accumbens changed the discharge rate of single neurons in the ventral globus pallidus and in the SI, LPO, and LHA. Typically, the responses were inhibition of neuronal discharge with latencies of 6 to 18 msec. Single pulse stimulation of the dorsolateral caudoputamen altered the discharge rate of single neurons in dorsal regions of the globus pallidus, with inhibition being the most frequently observed response. The results of these anatomical and electrophysiological experiments are complementary and indicate that fibers from the nucleus accumbens innervate the anteroventral region of the globus pallidus as well as the subpallidal region, while most fibers of the caudoputamen innervate the globus pallidus but not the subpallidal region. It appears, therefore, that these two components of the striatum have different output connections. The possible functional significance of these findings is discussed in relation to the projections of the subpallidal region, which may include an output to the mesencephalic locomotor region, and in relation to the nucleus accumbens afferents from the amygdala and hippocampal formation.

Animals↗

PubMed1984

A diffuse alpha MSH-immunoreactive projection to the hippocampus and spinal cord from individual neurons in the lateral hypothalamic area and zona incerta.

The course, distribution, and possible neurotransmitter specificity of a projection from the lateral hypothalamic area (LHA) and zona incerta to the hippocampal formation (dentate gyrus, Ammon's horn, subicular region, and entorhinal area) and spinal cord were examined anatomically in the adult rat. First, small injections of the fluorescent tracer fast blue were made into either the septal part of the dentate gyrus and Ammon's horn or the entorhinal area, and the distribution of retrogradely labeled cells was plotted. In each experiment many cells were labeled in the LHA and zona incerta, and little evidence for a topographically organized projection to different parts of the hippocampal formation was found. Second, a combined retrograde transport-immunofluorescence method was used to show that some 95% of the fast blue-labeled neurons in the LHA and zona incerta were also stained with an antiserum to the opiate peptide alpha-melanocyte-stimulating hormone (alpha MSH), but not an antiserum to adrenocorticotropin (ACTH)1-24. It was also found that small numbers of retrogradely labeled neurons were stained with antisera to somatostatin 14 and 28, dynorphin (1-17), and angiotensin II. Third, the distribution of alpha MSH-immunoreactive fibers was plotted, and they were found to form a diffusely organized plexus throughout all of the subfields of the hippocampal formation. These fibers were virtually eliminated after transections of the fimbria and the region between the entorhinal area and the caudal amygdala. Forth, the course of fibers from the LHA and zona incerta was examined with the anterogradely transported lectin Phaseolus Vulgaris Leucoagglutinin (PHAL). Such fibers reach the hippocampal formation by a dorsal route through the septal region and fimbria, and by a ventral route through the amygdala. And fifth, double retrograde transport and immunohistochemical methods were used to show that at least some alpha MSH-stained neurons in the LHA and zona incerta give rise to collaterals that innervate both the hippocampal formation and the spinal cord. Alpha MSH-stained fibers in the spinal cord also form a widely scattered plexus with no obvious circumscribed terminal fields. It is suggested that the diffusely organized projection from the LHA to the cerebral cortex and spinal cord may play a role in the general arousal associated with a variety of motivated behaviors.

Animals↗

PubMed2002

Enterostatin increases extracellular serotonin and dopamine in the lateral hypothalamic area in rats measured by in vivo microdialysis.

The effect of enterostatin injection into the rat lateral hypothalamic area (LHA) on serotonin and dopamine releases in extracellular space was investigated by in vivo microdialysis technique. The primary focus being to understand whether a small amount of enterostatin crossing the blood-brain barrier correlates with activity changes in serotonergic and dopaminergic nervous systems or not. We found a significant elevation in serotonin release in the LHA. The enterostatin perfusion also induced a smaller but significant increase in dopamine level than serotonin one. This result suggests that enterostatin plays some sort of role in the control of feeding of fat through the control serotonergic and dopaminergic satiety mechanism.

Animals↗

PubMed2005

Sex difference in the response of melanin-concentrating hormone neurons in the lateral hypothalamic area to glucose, as revealed by the expression of phosphorylated cyclic adenosine 3',5'-monophosphate response element-binding protein.

Because there are sex differences in feeding behavior in rats, we looked for a possible sex difference in the response to glucose of melanin-concentrating hormone (MCH) neurons in the lateral hypothalamic area using phosphorylated cAMP response element-binding protein (pCREB) as a marker of neural activity. Intact male rats and female rats at diestrus 2, proestrus, or estrus were fed normally or fasted for 48 h and injected with saline or glucose (400 mg/kg). Thereafter, preparations were subjected to immunohistochemical processing for the double staining of MCH and pCREB. Fasting increased the ratio of MCH neurons with pCREB (double-stained cells) in both male and female rats. In fasted rats, glucose injection decreased the ratio of double-stained cells more promptly in females than in males. The magnitude of decrease caused by glucose was greater at proestrus and estrus than at diestrus 2. Gonadectomy in males enhanced and in females attenuated the response of MCH neurons to glucose. Testosterone and estrogen replacement in males and females, respectively, restored the response of MCH neurons to glucose. The demonstrated sex differences in the response of MCH neurons to glucose correlated well with the gonadal steroid milieu; thus, MCH neurons may play an important role in sex differences in feeding behavior.

Animals↗

PubMed1985

Feeding behavior elicited by electrical stimulation of the lateral hypothalamic area in the rat: role of the adrenergic pathways and receptors.

To study the role played by neurotransmitters and their receptor mechanisms in the control of feeding behavior elicited by electrical stimulation, drugs that affect neurotransmission were injected via cannula electrodes into the lateral hypothalamic area. Pretreatment with noradrenaline (0.5 and 1.0 nmol) significantly increased the effect of hypothalamic stimulation on feeding, whereas injection of 1.0, 2.0 and 4.0 nmol of adrenaline or dopamine was ineffective. Phentolamine (40.0, 80.0 and 100.0 nmol) and propranolol (40.0, 80.0 and 120.0 nmol) induced a decrease in food intake, suggesting the involvement of both alpha and beta receptors in this mechanism. However, isoprenaline (20.0 nmol) also reduced food intake. Reduction of food intake by propranolol was probably related to the action of the local anesthetic. Alphamethyl-p-tyrosine (203.0 nmol), reserpine (32.8 nmol) and 6-hydroxydopamine (200.0 nmol) inhibited the feeding behavior elicited by electrical stimulation of the lateral hypothalamic area. These results suggest that electrical stimulation of the lateral hypothalamic area elicits feeding behavior by releasing noradrenaline. Alpha-adrenergic receptors seem to play a facilitatory role in feeding behavior.

Animals↗

PubMed1992

Functional and anatomical organization of cardiovascular pressor and depressor sites in the lateral hypothalamic area: I. Descending projections.

The present study describes the anatomical organization of projections from functionally defined cell groups of the lateral hypothalamic area. Cardiovascular pressor and depressor sites were identified following microinjection (5-50 nl) of 0.01-1.0 M L-glutamate or D,L-homocysteate into the anesthetized rat. Subsequent injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) or wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made into pressor or depressor sites and their connections with the brainstem and spinal cord were traced. Decreases in blood pressure (10-45 mmHg) and heart rate (20-70 bpm) were elicited from tuberal (LHAt) and posterior (LHAp) regions of the lateral hypothalamic area (LHA). Depressor neurons in the LHAt have descending projections to the central gray, dorsal and median raphe nuclei, pedunculopontine tegmental nucleus, pontine reticular formation, medial and lateral parabrachial nuclei, laterodorsal tegmental region, and medullary reticular formation including the region of the lateral tegmental field, nucleus ambigous, and rostrocaudal ventral lateral medulla. In contrast, descending projections from depressor neurons in the LHAp have dense terminal fields in the rostral, middle, and commissural portions of the nucleus of the solitary tract and the lateral tegmental field as well as the ventrolateral central gray, pedunculopontine tegmental nucleus, and medial and lateral parabrachial nuclei. Both the LHAt and LHAp have light projections to the intermediate region of the cervical and thoracic spinal cord. Increases in blood pressure (10-40 mmHg) and heart rate (20-70 bpm) were elicited almost exclusively from neurons located medial to the LHAt and LHAp in a region surrounding the fornix, termed the perifornical area (PFA). Pressor cells in the PFA have descending projections to the central gray, dorsal and median raphe nuclei, laterodorsal tegmental nucleus, and Barrington's nucleus as well as a light projection to the commissural portion of the nucleus of the solitary tract and the intermediate region of the cervical and thoracic spinal cord. The retrograde labeling observed in the WGA-HRP studies indicates that cells in most terminal fields have reciprocal projections to the pressor and depressor regions of the LHA. The results demonstrate that groups of neurons in the lateral hypothalamus with specific cardiovascular function have differential projections to the brain stem.

Amino Acids↗

PubMed1982

Efferent connections of the lateral hypothalamic area of the rat: an autoradiographic investigation.

The efferent projections of the lateral hypothalamic area (LHA) at mid-tuberal levels were examined with the autoradiographic tracing method. Connections were observed to widespread regions of the brain, from the telencephalon to the medulla. Ascending fibers course through LHA and the lateral preoptic area and lie lateral to the diagonal band of Broca. Fibers sweep dorsally into the lateral septal nucleus, cingulum bundle and medial cortex. Although sparse injections are found to the ventromedial hypothalamic nucleus, a prominent pathway courses to the dorsal and medial parvocellular subnuclei of the paraventricular nucleus. Labeled fibers in the stria medullaris project to the lateral habenular nucleus. The central nucleus of the amygdala is encapsulated by fibers from the stria terminalis and the ventral amygdalofugal pathway. The substantia innominata, nucleus paraventricularis of the thalamus, and bed nucleus of the stria terminalis also receive LHA fibers. Three descending pathways course to the brainstem: (1) periventricular system, (2) central tegmental tract (CTT), and (3) medial forebrain bundle (MFB). Periventricular fibers travel to the ventral and lateral parts of the midbrain central gray, dorsal raphe nucleus, and laterodorsal tegmental nucleus of the pons. Dorsally coursing fibers of CTT enter the central tegmental field and the lateral and medial parabrachial nuclei. The intermediate and deep layers of the superior colliculus receive some fibers. Fibers from CTT leave the parabranchial region by descending in the ventrolateral pontine and medullary formation; some of these fibers sweep dorsomedially into the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and nucleus commissuralis. From MFB, fibers descend into the ventral tegmental area and to the border of the median raphe and raphe magnus nuclei.

Amygdala↗