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Two distinct descending inputs to the cricothyroid motoneuron in the medulla originating from the amygdala and the lateral hypothalamic area.

1. The retrograde labelling study revealed that there are at least two independent descending pathways from the limbic system to the ventral medulla, i.e., the hypothalamo-medullary pathway and the amygdalo-medullary pathway. 2. The stimulation in the lateral hypothalamic area produced parasympathetic excitation and vocalization response: the recruited motor unit of CT muscle occurred in the late expiratory phase. By contrast, the stimulation at the medial part of the amygdala evoked sympathetic excitation and expiratory braking: the recruited motor unit of CT muscle occurred in the early expiratory phase or in the post-in-spiratory phase. 3. The present physiological study provided further important information on dual innervation of the cricothyroid muscle of the larynx: one motor unit with inspiratory firing is generated in the medulla, whereas the other motor unit with expiratory firing is evoked by a descending input from the limbic system.

Amygdala↗

Nociceptive and non-nociceptive responses of neurons in the medial subthalamic region and lateral hypothalamic area of cats and their relationship to the effects of morphine and pentazocine.

Single neuronal activity was recorded extracellularly from the Forel's field (FH), subthalamic region immediately rostral to the FH (STRF), rostral end of the medial subthalamic region (RE) and lateral hypothalamic area (LHA) of the anesthetized cats. Many of the FH, RE and LHA neurons were excited by nociceptive stimulation such as pinching the skin with serrated forceps and/or intra-arterial injection of bradykinin. These nociceptive neurons were also excited by non-nociceptive stimulation such as tap of deep tissues, bending hairs with an air-puff and/or joint rotation. On the other hand, inhibition by both nociceptive and non-nociceptive stimuli was seen in and around the rostral end of the FH including STRF. Their receptive fields were large. After intravenous administration of either morphine or pentazocine, most nociceptive neurons became unresponsive to nociceptive stimuli, although they were driven by non-nociceptive stimuli. This suggests that morphine and pentazocine have a specific antinociceptive action on these nociceptive neurons. Intravenous naloxone reversed the antinociceptive action of morphine, but failed to reduce the action of pentazocine. This differentiation has an important functional significance.

Animals↗

RECIPROCAL ACTIVITIES OF THE VENTROMEDIAL AND LATERAL HYPOTHALAMIC AREAS OF CATS.

Statistical treatment of recordings of spontaneous unit discharges from the ventromedial nucleus and the lateral area of the hypothalamus (the activities in one area being recorded while the other was stimulated) revealed significant reciprocal relations. The concept that glucose-sensitive neurons are present in the ventromedial nucleus was supported by the effects on the spontaneous unit discharges of injecting glucose and other-solutions intravenously.

Cats↗

An intragastric amino acid mixture influences extracellular amino acid profiles in the lateral hypothalamic area of freely moving rats.

We tested the effect of equicaloric loads of glucose (0.89 g) or a balanced amino acid mixture (0.85 g) on extracellular amino acid concentrations in the brains of freely moving rats. At 15:30 hours, the microdialysis probe was inserted into the lateral hypothalamic area of ambulatory rats, and food and water were removed. Dialysates were collected every 20 min from 1 h prior to gavage (18:00 hours) and until 3 h after the gavage. Amino acid concentrations in the dialysate were determined by reverse-phase HPLC. Following the amino acid gavage, extracellular amino acid concentrations significantly increased from baseline for alanine, isoleucine, leucine, methionine, threonine, tyrosine, and valine. Those elevations occurred within 20-40 min following the amino acid load, and lasted up to 100 min. After the glucose and water treatments, amino acid concentrations were either not affected or gradually diminished from baseline. We conclude that extracellular amino acid concentration in the lateral hypothalamus is influenced by the composition of food consumed.

Administration, Oral↗

Fibroblast growth factor receptor-1 in the lateral hypothalamic area regulates food intake.

Previous studies have shown that acidic and basic fibroblast growth fa ctor (aFGF and bFGF) and certain fragments of the aFGF N-terminal suppress food intake in rats due to their inhibitory actions on the glucose-sensitive neurons in the lateral hypothalamic area (LHA). The present study was planned to determine the role of FGF receptor-1 (FGFR-1), which was found in the LHA neurons of rats, on feeding regulation. The structure-activity relationship of aFGF fragments in feeding suppression was also investigated. An injection of anti-FGFR-1 antibody (250 and 350 ng) into the bilateral LHA significantly increased food intake. Synthesized aFGF fragments were infused into the III ventricle to elucidate the structure-activity relationship on the inhibition of feeding. Although aFGF-(1-29) did not affect food intake, [Ser16]aFGF-(1-29) (400 ng) and [Glu16]aFGF-(1-29) (400 NG), in which the cysteine residue at position 16 of aFGF(1-29) was replaced with structurally similar serine and glutamic acid, were observed to significantly inhibit food intake. These findings suggest that endogenous FGFR-1 in the LHA plays an important role in FGF-induced feeding suppression, while, in addition, the dissolving disulfide bond formation in aFGF fragments enhances their inhibitory effects on feeding.

Amino Acid Sequence↗

Alteration of the expression of the hypocretin (orexin) gene by 2-deoxyglucose in the rat lateral hypothalamic area.

Following an i.p. injection of 2-deoxyglucose (2DG), a nonmetabolizable analogue of glucose known to induce intracellular glucopenia, a progressive decrease in the level of hypocretin (Hcrt)/orexin mRNA was observed in the rat lateral hypothalamus while the melanin-concentrating hormone (MCH) expression in neighbouring neurons remained unaffected. This result together with the previously reported stimulation of Hcrt expression by insulin confirms that Hcrt neurons, but not MCH neurons, are sensitive to glucose availability and suggests that they respond through different mechanisms and/or different pathways to intracellular glucopenia and hypoglycemic conditions.

Animals↗

[Effect of acupuncture on level of monoamines and activity of adenosine triphosphatase in lateral hypothalamic area of obese rats].

OBJECTIVE: To study the mechanism of acupuncture in treating simple obesity. METHODS: Central nerve push-pull perfusion and biochemical technique were used to observe the effect of acupuncture on obese rats, and the obese parameters and the change of monoamine transmitters and activity of ATPase in the lateral hypothalamic area (LHA) of the obese rats were investigated. RESULTS: The levels of noradrenaline (NA) in LHA of obese rats were higher than those in the normal group, but the level of serotonin (5-HT) and the activity of ATPase in LHA of obese rats were lower than those of the normal rats. After acupuncture treatment, the weight of the obese rats reduced, while the level of NA in LHA reduced and the 5-HT and activity of ATPase increased (P < 0.05, P < 0.01). CONCLUSION: The effective regulation on LHA of obese rats is possibly one of the key factors in the anti-obesity of acupuncture.

Acupuncture↗

Electrophysiological characteristic of the ventromedial hypothalamic nucleus and lateral hypothalamic area in normally fed and 24 hour food deprived conscious sheep.

We registered telemetrically the spontaneous electrical activity of the hypothalamic ventromedial nucleus (VMH) and the lateral hypothalamic area (LH) in conscious adult sheep-male, with implanted electrodes,-in a state of normal feeding or after 24 hour food deprivation. The frequency of electrical activity, the amplitude of electrical activity and the frequency by Fourier analysis were evaluated. The frequency of electrical activity was found to be approximately the same in the VMH and LH with mean values +/- S.E.M. 11.5 +/- 0.5 Hz in feed sheep. The amplitude of electrical activity in the VMH was higher compared with the LH, with mean absolute values +/- S.E.M. 41.5 +/- 2.7 microV in the VMH and 35.5 +/- 3.2 microV in the LH. The Fourier analysis showed that from the total amount of harmonic frequencies-the first one i.e. the basic frequency represented 48-56%, the rest are higher frequencies. In sheep after 24 hour food deprivation the frequency of electrical activity decreased on 9.4-9.6 Hz in average in both regions under study and the absolute values of the amplitude of electrical activity increased. The mean absolute value +/- S.E.M. was 115 +/- 5.2 microV in the VMH and 101.2 +/- 3.0 microV in the LH. Along with theses changes we found by Fourier analysis that in the total amount of harmonic frequencies the basic frequency decreased by 6% due to the greater amount of higher harmonic frequencies.

Animals↗

Extracellular serotonin in the lateral hypothalamic area is increased during the postejaculatory interval and impairs copulation in male rats.

Serotonin (5-HT) is generally inhibitory to masculine sexual behavior. It has been suggested that 5-HT released after ejaculation may promote the sexual quiescence of the postejaculatory interval (PEI). The following experiments were conducted to test (1) whether extracellular 5-HT increases in either the anterior lateral hypothalamic area (LHAA) or the medial preoptic area (MPOA) of male rats after ejaculation; (2) whether increasing 5-HT in these sites, by microinjecting the selective serotonin reuptake inhibitor alaproclate, could inhibit copulatory abilities; and (3) whether copulation deficits produced by alaproclate were attributable to locomotor impairments. The effects of local application of alaproclate on extracellular 5-HT levels in the LHAA and the MPOA were also tested. Extracellular serotonin was measured in all experiments using in vivo microdialysis. Ejaculation was correlated with enhanced 5-HT release from the LHAA; no 5-HT increases were observed before ejaculation, and levels were decreased toward basal values during a subsequent copulatory series. Elevating 5-HT in the LHAA by microinjecting alaproclate inhibited copulation by increasing the latency to mount, intromit, and ejaculate. This inhibition did not result from nonspecific locomotor impairments. In the MPOA, 5-HT release remained stable throughout copulation, and microinjecting alaproclate into this site did not significantly alter sexual behavior. These data support the large body of evidence suggesting that 5-HT is inhibitory to masculine sexual behavior. Furthermore, the LHAA, but not the MPOA, may be one site responsible for serotonergic inhibition of copulation during the PEI.

Alanine↗

Activin antiserum infused into the lateral hypothalamic area affects operant behavior of rats fed lysine-deficient diet.

Rats were trained to maintain a high rate of bar pressing to receive 50-mg pellets of a complete diet when given a lysine-deficient (Lys-def) diet ad libitum. This bar-pressing behavior was significantly inhibited when rats were also allowed ad libitum access to 0.4 M Lys to drink. A brain activin system may modulate motivation to engage in bar-pressing behavior, since previous work has established that antagonism of activin by infusion of inhibin or follistatin, but not activin, into the lateral hypothalamic area (LHA) also inhibits bar-pressing behavior. The present study sought to clarify whether the effect of inhibin or follistatin might be mediated by antagonism of endogenous activin or by a separate direct effect of inhibin or follistatin. Thus, we infused an antiserum, which specifically inhibits activin A activity, into the LHA. Infusion of antiserum greatly inhibited bar-pressing behavior of rats fed a Lys-def diet and was additive with Lys consumption further to decrease bar pressing. Ad libitum Lys consumption was unchanged from control levels, indicating that it is likely that an endogenous activin system in the LHA mediates behavioral responsiveness when rats are fed a Lys-def diet but does not appear specifically to affect appetite for Lys.

Activins↗

Nonadrenergic relaxation of the cat cervical trachea evoked by stimulation in the lateral hypothalamic area.

The purpose of this study was to evaluate hypothalamic contributions to control of tracheal tone. We found hypothalamic sites where electrical stimulation (60-90 microA: 1 ms pulse duration: 50 Hz: 5-10 s) and microinjection of L-glutamate (5-50 nmol) produced tracheal relaxation responses along with decreased blood pressure and heart rate in anesthetized, spontaneously breathing cats. Responsive sites were located in anterior (LHAa) and tuberal (LHAt) regions of the lateral hypothalamic area indicating that neuronal cells in those regions are responsible for development of tracheal relaxation. In a second experiment, we evaluated possible pathways mediating the tracheal relaxation response elicited by LHA stimulation. Tracheal relaxation was not attenuated by beta-adrenergic blockade (propranolol i.v., 0.2-0.5 mg/kg); the response is mediated by nonadrenergic mechanisms Muscarinic blockade (atropine i.v.) at doses of 0.05-0.1 mg/kg almost abolished tracheal tone during spontaneous breathing, and LHA stimulation evoked a small, insignificant reduction of tracheal tone. Cervical vagotomy completely abolished the trachea tone, and LHA stimulation no longer evoked the tracheal relaxation. These results indicate the existence of a nonadrenergic descending pathway within the vagal efferents, which is linked with behavioral control arising from LHA, and causes trachea relaxation.

Adrenergic Fibers↗

Differential effect of the damage to the lateral hypothalamic area on hippocampal theta rhythm during waking and paradoxical sleep.

Hippocampal theta rhythm was analyzed in rats subjected to bilateral, electrolytic lesions of the lateral hypothalamic (LH) region at different levels of its rostro-caudal axis. It was found that damage to the LH disturbed the hippocampal theta activity both during waking and paradoxical sleep. The main effect consisted in the lowering of the theta frequency. Typically, a decrease of frequency was accompanied by an increase of amplitude during waking, and an amplitude fall during paradoxical sleep. Extensive lesions increased the amount of rhythmic slow activity during waking and induced long trains of immobility-related theta. The general picture of impairments of the hippocampal theta rhythm in particular subjects depended on the size of the lesion and, to some extent, also on its localization within the LH. It is concluded that LH region contains systems of fibers which transmit impulses from the brain stem reticular formation to the prosencephalic structures generating the rhythmicity of theta.

Animals↗

Preprohypocretin (orexin) and prolactin-like immunoreactivity are coexpressed by neurons of the rat lateral hypothalamic area.

Recently, two new neuropeptides named hypocretins I and II (Hcrt) have been described in the rat lateral hypothalamus. The distribution of the neurons expressing these new peptides is similar to that of neurons described in the literature as prolactin (PRL) immunoreactive neurons and specifically labeled by an antiserum (AS) raised against ovine prolactin (oPRL). In this study, we report that every neuron labeled by immunohistochemistry or in situ hybridization for Hcrt is also labeled by the oPRL-AS, and conversely. Furthermore, the labeling of the oPRL-AS is inhibited when this AS is pre-incubated with the 104-109 fragment of the preproHcrt, thus indicating that the oPRL-AS is recognizing an epitope carried by this particular fragment of the preproHcrt. Our previous experimental work on these neurons showed that they may be involved in energy metabolism and water balance, which is in agreement with the current literature about Hcrt functions.

Animals↗

Insulin-induced hypoglycemia increases preprohypocretin (orexin) mRNA in the rat lateral hypothalamic area.

The recent identification of two peptides named hypocretins (Hcrt), and expressed in neurons of the rat tuberal lateral hypothalamus (LHA) previously detected by an ovine prolactin antiserum, led us to revisit some experimental procedures intented to understand the physiological roles of these neurons. In the present study, rats received intraperitoneal injections of insulin and/or glucose. Immunocytochemical observations and quantitation of in situ hybridization signals pointed out a clear stimulation of Hcrt neurons following the sole injection of insulin in hypoglycemic but not in hyperglycemic conditions. This result, together with the robust appetite boosting effect of Hcrt reported elsewhere, suggests the involvement of Hcrt neurons in the control of food intake.

Animals↗

[The dynamics of the electrical activity of the forebrain structures in rats in the waking-sleep cycle after electrostimulations of the emotiogenic zones in the lateral hypothalamic area].

One series of ES (multiple priming) of emotion-positive zone (1) ore the ambivalent zone (2) of lateral hypothalamus (LH) during one hour in Wistar male rats resulted in disorders of the W-S cycle: reduction of deep slow-wave sleep down to about 4.7% (zone 1) and down to 0.9% (zone 2), as well as a considerable reduction of REM sleep down to 0.8% (zone 1). The results of the analysis of bioelectrical brain activity dynamics in the W-S cycle suggest that hyperactivation of emotiogenic zones generated by ES is responsible for the establishment of paroxysmal states corresponding to the second and the third stages of kindling and the disorders of the W-S cycle. Kindling is assumed to form due to emotiogenic zones of the brain involved in to this process. The longer bursts of hypersynchronous bioelectrical activity in the cortex than in the subcortical structures during transient stages of sleep may be in favour of more active participation of phylogenetically younger brain structures in the process of epileptogenesis.

Animals↗

Drinking attenuates the noradrenaline release in the lateral hypothalamic area induced by angiotensin II activation of the subfornical organ in rats.

Experiments were conducted to investigate the role of noradrenergic systems in the lateral hypothalamus area (LHA) in the water intake caused by injection of angiotensin II (ANG II) into the subfornical organ (SFO) in rats. Intracerebral microdialysis techniques were utilized to quantify the extracellular content of noradrenaline (NA) in the LHA. Microinjection of ANG II into the SFO significantly increased NA release in the LHA when water was not available for drinking. The increase in the release of NA in the LHA was significantly attenuated by water intake. In urethane-anesthetized rats, injections of ANG II into the SFO significantly enhanced the release of NA in the LHA that accompanied an elevation in mean arterial pressure (MAP). Intravenous administration of the alpha-agonist metaraminol, on the other hand, significantly decreased the NA release in the LHA that accompanied an increase in MAP, suggesting that the enhanced NA release in the LHA caused by ANG II into the SFO may be not mediated by increasing in arterial pressure. These results show the involvement of the noradrenergic systems in the LHA in the dipsogenic response induced by angiotensinergic activation of the SFO.

Adrenergic alpha-Agonists↗

Participation of alpha-1 and alpha-2 adrenoceptors of the lateral hypothalamic area in water intake, and renal sodium, potassium and urinary volume excretion induced by central administration of angiotensin II.

The circumventricular structures and the lateral hypothalamus (LH) have been shown to be important for the central action of angiotensin II (ANGII) on water and electrolyte regulation. Several anatomical findings have demonstrated neural connection between circumventricular structures and the LH. The present experiments were conducted to investigate the role of the alpha-adrenergic antagonists and agonistic injected into the LH on the water intake, sodium and potassium excretion elicited by injections of ANGII into the lateral ventricle (LV). The water intake was measured every 30 min over a period of 120 min. The sodium, potassium and urinary volume were measured over a period of 120 min in water-loaded rats. The injection of ANGII into the LV increased the water intake, which was reduced by previous injection of clonidine (an alpha-2-adrenergic agonist) into the LH. The injection of yohimbine (an alpha-2-adrenergic antagonist) and prazosin (an alpha-1-adrenergic antagonist) into the LH, which was done before injecting ANGII into the LV, also reduced the water intake induced by ANGII. The injection of ANGII into the LV reduced the sodium, potassium and urinary volume. Previous treatment with clonidine attenuated the action of ANGII in reducing the sodium, potassium and urinary volume, whereas previous treatment with yohimbine attenuated the effects of ANGII but with less intensity than that caused by clonidine. Previous treatment with prazosin increased the inhibitory effects of ANGII in those parameters. The injection of yohimbine and prazosin, which was done before the injection of clonidine, attenuated the effect of clonidine on the ANGII mechanism. The results of this study led us to postulate that when alpha-2-adrenergic receptors are blocked, the clonidine may act on the imidazoline receptors to produce its effects on the ANGII mechanism. We may also conclude that the LH is involved with circumventricular structures, which present excitatory and inhibitory mechanisms. Such mechanisms are responsible for regulating the renal excretion of sodium, potassium and water.

Angiotensin II↗

[Intracellular regeneration of neurons in the rat lateral hypothalamic area of the brain after resumption of food intake].

Electron microscopy was used to explore changes in intracellular regeneration processes in neurons of the anterior, medial and posterior parts of the lateral hypothalamus area (LHA) of rats at various time (10, 20, 30, 50 and 70 days) after resumption of food perception. Ultrastructural changes observed during 7 days of food deprivation in intact neurons were of a reversible character. Recovery processes initially appeared and finished earlier in the neurons of medial (day 30) and anterior (day 50) parts of the LHA, in the posterior part of LHA the normalization of the neuronal structure was slower and was over only by the 70th day after the resumption of food reception. The above data are both of theoretical and practical importance, serving as a base for the study of directed treatment of diseases caused by hunger.

Animals↗