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[Activity of neurons of the hypothalamic suprachiasmatic nuclei and circadian rhythms: the role of the suprachiasmatic nuclei in rhythmic activities of neurons in the lateral hypothalamic area and ventromedian nuclei and the control of the pineal gland].

Unit activity of lateral hypothalamic area (LHA) and ventromedian nuclei (VMN) was recorded in urethane anesthetized male rats. A 5 to 10 sec, a 3 to 5 min and a circadian rhythmicity were observed. In about 15% of all neurons, spontaneous activity of LHA and VMN showed reciprocal relationships. Subthreshold stimuli applied at a slow rate in the septum and the suprachiasmatic nuclei (SCN) suppressed the rhythms without changing firing rates. On the other hand stimulation of the optic nerve at a rate of 5 to 10/sec increased firing rates in one third of neurons of SCN. Iontophoretically applied acetycholine increased 80% of tested neurons of SCN, whereas norepinephrine, dopamine and 5HT inhibited 64%, 60% and 75% of SCN neurons, respectively. These inhibitions were much stronger in neurons, the activity of which was increased by optic nerve stimulation. Stimulation of the SCN inhibited the tonic activity in cervical sympathetic nerves. These data suggest that SCN plays a significant role in controlling the rhythmic activity of LHA, VMN and the pineal gland. Dopamine and 5HT may be involved in regulation of the firings of SCN neurons.

Acetylcholine↗

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

The ascending efferent projections of the neurons of the anterior (LHAa), central (LHAc) and posterior (LHAp) parts of the lateral hypothalamic area (LHA) have been studied using an autoradiographic analysis of the anterograde axonal transport after local injection of tritiated amino acids. Our results show that LHA regions have common projections particularly to the thalamus and to the hypothalamus. They also demonstrate the existence of differential projections: i.e. an anteroposterior gradient of projection sites according to anterior, central and posterior localisation of the LHA neurons. The LHAa neuronal projections terminate in the lateral septal area; the LHAc projections innervate the frontal cortex while LHAp neurons send their projections to the olfactory bulb and innervate both the cerebral cortex and the hippocampus. Only the LHAp neurons project measurably to the globus pallidus, the caudate putamen and the nucleus accumbens.

Animals↗

Action of the lateral hypothalamic area on subfornical organ neurons projecting to the supraoptic nucleus in the rat.

The activity of all subfornical organ neurons (N = 20) that were antidromically identified by electrical stimulation of the rat hypothalamic supraoptic nucleus region was excited by microiontophoretically applied angiotensin II. Electrical stimulation of the lateral hypothalamic area produced either an excitatory response (N = 12) or no effect (N = 8) in the activity of identified subfornical organ neurons. The excitatory responses to iontophoretically applied angiotensin II or stimulation of the lateral hypothalamic area were blocked by iontophoretically applied saralasin, an antagonist of angiotensin II.

Angiotensin II↗

Changes in single unit activity in the lateral hypothalamic area of goats during feeding.

In order to clarify the location of feeding centers in the ruminant brain, this study used a single-unit activity (SUA) recording electrode to investigate the existence of appetite-regulating neurons in the lateral hypothalamic area (LHA) in goats. Seven male Japanese Saanen goats were used in the experiment. The animals were fed twice daily, once in the morning (1000 to 1200) with 1.5 kg of roughly crushed alfalfa hay cubes, and once in the afternoon (1600 to 1800) with 200 g of commercial ground concentrate feed. The animals were allowed free access to drinking water. In this study, the animals were surgically operated on to position the recording electrode in the LHA. Recordings of SUA were carried out continuously over a 2.25-h period beginning 15 min prior to the commencement of morning feeding. The eating rates of crushed alfalfa hay cubes were highest 10 min after feeding commencement, but decreased sharply by the time 40 min had elapsed. The cumulative feed intake after the completion of the 2-h feeding period was 1164 +/- 38 g. The cumulative water intake upon the conclusion of the 2-h feeding period was 2422 +/- 107 mL. This study recorded 31 units, of which five showed a response to feeding and altered their firing rates. In response to a sharp increase in eating rates, all five units increased their firing rates to a level higher than that of prefeeding (P < 0.05). As the animals reached a level of satiety (eating rates declined to very low levels), firing of units I and II stopped completely, while the firing rates of units III, IV, and V decreased. Examination of a serial histological section confirmed that the five units in which changes in firing rates with feeding were observed were all located in the dorsolateral hypothalamic area close to the fornix. The LHA neurons recorded in this experiment characteristically showed neuronal activity increases at high levels of feeding, but decreases at low levels. The results suggest that there are cells located in the LHA of goats that are active in the physiological regulation of hay (dry forage) intake.

Animal Feed↗

Osmotic stimulation differentially affects cellular levels of corticotropin-releasing hormone and neurotensin/neuromedin N mRNAs in the lateral hypothalamic area and central nucleus of the amygdala.

To investigate the effects of osmotic stimulation on neural circuits concerned with non-neuroendocrine aspects of homeostatic regulation, the levels of the mRNAs coding for corticotropin-releasing hormone (CRH) and neurotensin/neuromedin N (NT/NMN) in the lateral hypothalamic area (LHA) and central nucleus of the amygdala (CEA) of animals given 2.5% saline to drink overnight were measured semiquantitatively using in situ hybridization. Overnight osmotic stimulation leads to converse effects on the levels of these two mRNAs in different anatomical regions; increased levels of both mRNAs are seen in the LHA, but levels decrease in the CEA. While a number of previous studies have shown that ppCRH mRNA in the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus may contribute to the neuroendocrine response to osmotic stimulation, the present results show that in response to osmotic stimulation neurons located outside the PVH and SO may also modulate their synthetic potential, not just for CRH but also NT/NMN. These results suggest that a physiological stimulus may modulate the levels of two peptides previously identified in circuits projecting from the forebrain to nuclei in the brainstem, and as such, CRH and NT/NMN may participate in the regulation by the forebrain of the autonomic and/or behavioral responses of the animal to dehydration. Furthermore, these data show that a particular stimulus has opposite effects on the level of both peptide mRNAs when expressed in two different cell groups, suggesting first, that these peptides may have more than one role in the response, and second, the existence and influence of differential control mechanisms.

Amygdala↗

Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia.

Orexin-A and -B (also known as hypocretin-1 and -2) are neuropeptides which stimulate food intake when administered intracerebroventricularly. Orexins are specifically localized in neurons within and around the lateral hypothalamic area (LHA). Previous electrophysiological studies have demonstrated that some neurons in the LHA are activated by hypoglycemia, and are therefore termed 'glucose-sensitive neurons'. In the present study, we examined whether orexin-containing neurons are activated in the hypoglycemic states, using Fos-like immunoreactivity (FLI) as a marker of neuronal activation. We observed that FLI was induced in the LHA by acute insulin treatment. Double staining with anti-Fos and anti-orexin antibodies revealed that up to 33% of the orexin-containing neurons in the LHA also expressed FLI under the hypoglycemic condition. These results suggest that some populations of neurons which contain orexins are activated under hypoglycemic conditions.

Animals↗

Receptors in lateral hypothalamic area involved in insular cortex sympathetic responses.

Previous evidence has shown that sympathetic nerve responses to insular cortical (IC) stimulation are mediated by synapses within the lateral hypothalamic area (LHA) and ventrolateral medulla. The present study determined the receptor(s) involved at the synapse in the LHA associated with stimulation-evoked IC sympathetic responses. Twenty-seven male Wistar rats were instrumented for renal nerve activity, arterial pressure, and heart rate recording. The right IC was stimulated with a bipolar electrode (200-1,000 microA, 2 ms, 0.8 Hz) resulting in sympathetic nerve responses. Antagonists were then pressure injected into the ipsilateral LHA (300-500 nl). Kynurenate (250 mM) injections resulted in 51 +/- 8% (range 0-100%) block of IC-stimulated sympathetic nerve responses. Similarly, the N-methyl-D-aspartic acid (NMDA)-receptor antagonist DL-2-amino-5-phosphonopentanoic acid (200 microM) resulted in an inhibition (82 +/- 8%; range 51-100%) of IC-stimulated sympathetic responses. Injection of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (200 microM) had no effect on IC sympathetic responses. Injection of antagonists to GABA, acetylcholine, and adrenergic receptors was also without effect. No antagonist injections had any effects on baseline sympathetic nerve discharge, arterial pressure, or heart rate. These results suggest that the IC autonomic efferents projecting to the LHA utilize NMDA glutamatergic receptors.

2-Amino-5-phosphonovalerate↗

Electrical stimulation of lateral hypothalamic area and behavioural sequences in a lacertid lizard.

The observed transition frequencies of behaviour patterns were obtained for isolated lizards (Gallotia galloti), as well as those expected if the patterns were independent. The transitions differing significantly from random were calculated when: (1) the animals had an electrode in their lateral hypothalamic area (I); (2) they were electrically stimulated (S). The index O-E (O = observed transition frequency; E = expected one) was used to extract the statistical significance of the behaviour transitions. The Friedman and Wilcoxon tests, used to compare the relative transition frequencies between I, S and a first control (C) condition, showed that the main effects during the stimulation period were a decrease in the relative frequency of some transitions involving the climbing pattern and an increase in others including some exploration patterns.

Animals↗

Functional and anatomical organization of cardiovascular pressor and depressor sites in the lateral hypothalamic area. II. Ascending projections.

Microinjections of L-glutamate or D,L-homocysteic acid were used to stimulate cell bodies in the region of the lateral hypothalamic area (LHA) selectively. Subsequent iontophoretic injections of Phaseolus vulgaris-leucoagglutinin or pressure injections of wheat germ agglutinin-horseradish peroxidase were made into regions containing identified pressor and depressor sites and their connections with the forebrain and cerebral cortex were traced. The results indicate that decreases in blood pressure (10-45 mm Hg) and heart rate (20-70 bpm) could be elicited from tuberal (LHAt) and posterior (LHAp) sites in the LHA and that these regions have ascending projections to the insular cortex, the ventral forebrain including the septal-diagonal band of Broca complex, the ventral palladium, substantia innominata, amygdala, and the lateral preoptic area. In contrast, increases in blood pressure (10-40 mm Hg) and heart rate (20-70 bpm) were elicited primarily from neurons located adjacent to the fornix in the perifornical area (PFA). Injections of tract tracers into this region produced terminal labeling that differed markedly from the pattern seen following injections of tracer into depressor sites in the LHA. In addition, the pattern of anterograde labeling seen following injections of tracer into the anterior PFA differed from that seen following injections of tracer into the posterior PFA. Injections of tracer into the anterior PFA resulted in dense terminal labeling in the medial preoptic area and the parvicellular paraventricular nucleus of the hypothalamus whereas injections into the posterior PFA resulted in dense terminal labeling in the lateral septal nucleus, nucleus accumbens, bed nucleus of the stria terminalis, as well as the medial preoptic area and the parvocellular paraventricular nucleus of the hypothalamus. The results demonstrate that the posterolateral hypothalamus of the rat contains two regions with specific cardiovascular function and highly organized connections with diencephalic, forebrain, and cortical structures.

Afferent Pathways↗

Lateral hypothalamic area neurotransmission and neuromodulation of the specific cardiac effects of insular cortex stimulation.

Microstimulation of the rat posterior insular cortex in phase with the ECG R wave elicits pure cardiac effects unaccompanied by changes in blood pressure or respiration. This technique has successfully demonstrated cardiac chronotropic organisation and arrhythmogenesis within the insula. Pathways exist linking the insular cortex with the lateral hypothalamic area (LHA). Similarly, the LHA has previously been shown to mediate the sympathetic and blood pressure effects of insular cortex stimulation. Therefore it was anticipated that the tachycardia elicited by insular phasic microstimulation would be responsive to LHA manipulations. Insular tachycardia sites in 28 chloralose-anesthetised male Wistar rats were phasically stimulated once with each cardiac cycle using 500 microA for 1 min before and after microinfusions (390 nl) into the LHA. The insular tachycardia response was abolished by LHA microinfusions of the synaptic blocker cobaltous chloride (4 mM). LHA microinjection of kynurenic acid (250 mM) attenuated insular tachycardia by 95%. Microinjection of naloxone (30 mM) similarly attenuated the tachycardia by 95%. Met-enkephalin (3.5 mM) was without effect on this response whereas Leu-enkephalin (3.5 mM) and neuropeptide Y (0.01 mM) (NPY) doubled the magnitude of the tachycardia. Dynorphin (0.12 mM), a specific kappa opioid receptor agonist, augmented the response to stimulation of insular tachycardia sites 8-fold. Consequently, it is suggested that the LHA contains an obligatory synapse mediating insular tachycardia and that glutamate is the likely neurotransmitter at this site. Neuromodulation of insular tachycardia may be effected by opiate kappa and NPY receptors, a finding of considerable clinical relevance.

Animals↗

Reciprocal IL-1 beta gene expression in medial and lateral hypothalamic areas in SART-stressed mice.

Specific alteration of rhythm of temperature (SART) stress has been found to induce thymic atrophy via activation of the hypothalamus-pituitary-adrenal (HPA) axis. We demonstrate here that SART stress induces increment of IL-1 beta mRNA levels in the medial hypothalamic area (MHA) and decrement of IL-1 beta mRNA levels in the lateral hypothalamic area (LHA). The altered levels of IL-1 beta expression in these loci return to those of non-stressed mice upon cessation of the stress. These data imply that the reciprocal wave of SART stress-induced IL-1 beta gene expression in MHA and LHA may contribute to activation of the HPA axis and the resulting immunological dysfunction.

Animals↗

Astrocytic gap junctions in the rat lateral hypothalamic area.

An extensive system of gap or nexus junctions has been found between astrocytic processes in the neuropil of the lateral hypothalamic area in the albino rat. These specialized interastrocytic junctions occur in regions of high synaptic density where neural processes are separated by the interconnected glial system. In this study, 90% of the gap junctions observed in the lateral hypothalamic neuropil are in the immediate proximity of synaptic terminals. The close morphological relationship of these glial gap junctions with synaptic contacts suggests that they may play a significant role in the process of synaptic transmission.

Animals↗

Expression of immunoregulatory cytokines in neurons of the lateral hypothalamic area and amygdaloid nuclear complex of rats immunized against human IgG.

Present results showed that interleukin-1 (IL-1), IL-6 and transforming growth factor-beta (TGF-beta) were constitutively expressed in the supraoptic and paraventricular nuclei of the rat hypothalamus. Immunoreactive cells were also detected, but to a lesser extent, in other parts of hypothalamus as well as in the cerebral cortex. In rats immunized with IgG, there was moderate increase in immunoreactivities of the cytokines. A notable feature, however, was the induction of the cytokine expression in the lateral hypothalamic area and the amygdaloid nuclear complex, suggesting that the neurons in these two areas are involved in possible immune regulation.

Amygdala↗

Circadian and other rhythmic activity of neurones in the ventromedial nuclei and lateral hypothalamic area.

1. The frequency of firing was simultaneously recorded from single neurones of the ventromedial nuclei (VMN) and the lateral hypothalamic area (LHA) in urethane anaesthetized rats for many hours. 2. There were circadian changes of VMN and LHA neurone activity. The pattern of this circadian rhythm is as follows: throughout the day LHA neurones show higher activity than that of VMN, as indicated by higher frequency and more fluctuations in their rates of firing. In late afternoon the discharge rate of LHA neurones increases further, showing oscillations of short duration. In the early evening hours LHA neurone activity gradually goes down, as the VMN neurones become active. Throughout the night, VMN neurones are more active than those of LHA, just the opposite of the day period. In early morning hours VMN neurones gradually become quiet, while LHA neurones begin to show activity. 3. Superimposed on the circadian rhythm, at certain periods of the day, VMN and LHA neurones showed short duration oscillations in rate of firing, roughly every 7-15 sec and every 3-5 min. 4. Activities in neurones of the VMN and LHA were reciprocally related; a decrease in firing rate of one was associated with an increase in the other. This phenomenon was shown clearly by analysis of auto- and cross-correlation functions of firing patterns of VMN and LHA neurones. 5. The effects of stimulations of the prefrontal cortex and splanchnic afferents on VMN and LHA neurones depended on the basic firing frequency, thus they varied with the time of day. Definite relationships exist between basic firing frequency of a cell and the magnitude of changes evoked by these stimuli. Reactions of VMN and LHA neurones were the opposite in most instances. Septal stimulations (at more than 10/sec) always produced inhibition of LHA neurone activity. 6. Intravenous injection of glucose inhibited LHA neurones and accelerated firing of VMN cells. This was true during the day period as well as at night when background activities of VMN and LHA neurones were different from that of the day. 7. Stimulation of the septal area with subthreshold pulses at a low rate (1-0.3/sec) suppressed or altered oscillations in firing frequency of LHA neurones. Severance of connection between LHA and structures caudal thereto had no effect on LHA neurone firing rates or rhythms. Sections between the septal area and LHA, however, abolished or greatly altered the oscillatory rhythms of LHA cell activity, although spontaneous discharges continued at a somewhat lower rate for periods of hours. 8. Stimulation of suprachiasmatic nuclei with weak intensity and low frequency also changed oscillatory fluctuations in firing of LHA neurones. 9. Possible origins of circadian rhythm and oscillations of short duration in firing pattern of VMN and LHA neurones were discussed.

Action Potentials↗

Renal sodium handling after noradrenergic stimulation of the lateral hypothalamic area in rats.

1. The participation of special nephron segments in the renal control of sodium handling after adrenergic stimulation was investigated by determining lithium clearance in groups of 5-12 male Wistar rats (230-300 g) microinjected with noradrenaline into the lateral hypothalamic area (LHA). 2. Microinjection of noradrenaline (12.5 to 100.0 nmol/microliters) into the LHA promoted a significant decrease in proximal sodium reabsorption (controls, 86.5 +/- 1.3; 12.5, 81.4 +/- 2.0; 25.0, 72.6 +/- 2.4; 50.0, 75.4 +/- 1.8 and 100.0, 77.2 +/- 1.7%) and a dose-related increase in distal sodium reabsorption (control, 13.4 +/- 1.6; 12.5, 18.4 +/- 1,25.0, 26.9 +/- 2.9; 50.0, 24.1 +/- 2.7; 100.0, 22.1 +/- 1.9%) with no significant changes in creatinine clearance. Fractional sodium reabsorption after different noradrenaline concentrations was significantly reduced in the proximal nephron sites up to the concentration of 25.0 nmol/microliter. Beyond this concentration, a smaller but progressive increase in fractional sodium reabsorption was observed in the post-proximal segment. 3. These findings suggest an effective participation of proximal and post-proximal nephrons in natriuresis after lateral hypothalamic noradrenergic stimulation.

Analysis of Variance↗

Local perfusion of mCPP into ventromedial hypothalamic nucleus, but not into lateral hypothalamic area and frontal cortex, inhibits food intake in rats.

RATIONALE: The serotonergic (5-hydroxytryptamine, 5-HT) system is extensively implicated in feeding behavior. In recent years, 5-HT receptors have been classified into 14 subtypes, and activation of 5-HT1B and 5-HT2C receptors inhibits food intake in rats. However, the precise functions in local brain areas of these receptor subtypes are unclear. OBJECTIVES: Frontal cortex (FC), lateral hypothalamic area (LH), or ventromedial hypothalamic nucleus (VMH) are involved in control of feeding behavior. We investigated the effects of 5-HT1B and 5-HT2C receptor stimulations in the three local brain areas on feeding behavior and on 5-HT metabolism. METHODS: We perfused mCPP, 5-HT(1B/2C) agonist, at multiple doses via a microdialysis probe into the three local brain areas and observed food intake. Extracellular concentrations of 5-HT and 5-HIAA were measured simultaneously. RESULTS: Perfusion of 1 mM mCPP into VMH, but not into LH nor FC at any dose, induced significant reduction of food intake compared with control. The extracellular concentrations of 5-HT were markedly increased in all three areas, but the concentrations of 5-HIAA were not changed by mCPP perfusions. CONCLUSIONS: These results indicate that the effects of 5-HT1B or 5-HT2C receptor activation on feeding behaviors depended on the brain regions, and that 5-HT1B or 5-HT2C receptors in VMH, but not in FC or in LH, play important roles in the regulation of food intake. The results also suggested that mCPP acts not only as a 5-HT(1B/2C) agonist, but also as a 5-HT releaser or as a re-uptake inhibitor. Further studies using antagonists should be conducted.

Animals↗

Transient aphagia produced following bilateral destruction of the lateral hypothalamic area and quinto-frontal tract of chicks.

Six groups of broiler chicks, Gallus domesticus, sustained bilateral lesions to specific neural structures residing in the lateral hypothalamic and thalamic areas. In contrast to past data reported for the albino rat, the pigeon, Columba livia and barbary dove, Streptopelia risoria, bilateral destruction of the chick lateral hypothalamic area (LHy), quinto-frontal tract (QF), and stratum cellulare externum (SCE) resulted in transient aphagia and rapid recovery of lost body weight. Similarly, bilateral destruction of the nucleus reticularis superior (RS) and nucleus intercalatus (ICT) resulted in a temporary 1--3 day period of aphagia with body weight returning to pre-operative levels in approximately 4 days. Bilateral destruction of the ansa lenticularis (AL) resulted in a more prolonged period of aphagia (4 days) and an average 8-day period to recover lost body weight. Additional data suggest that more persistent aphagia can be induced following lesions to the posterior hypothalamus and midbrain. Specifically, bilateral lesions which destroyed the following combination of neural structures resulted in prolonged aphagia: AL, QF and posterior LHy; AL and posterior nucleus of the AL (ALp); and AL, ALp and QF. It is suggested that the AL and ALp contain neurons which are part of a more complex system that modulates or controls motor activity and feeding behavior in birds.

Animals↗