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Precocious development of the testes in chicks following parasagittal knife cuts of the lateral hypothalamic area.

Early development of the testes was effected in chicks following parasagittal knife cuts through the entire lateral hypothalamic area (extending from preoptic to mammillary region). Associated with the accelerated development of the testes was a significantly reduced body weight compared to sham-operated controls (P less than 0.05). Bilateral cuts involving solely the anterior or posterior hypothalamic regions did not cause precocious puberty. At this time the critical fiber tracts which were bilaterally sectioned and their associated neurohumoral mechanism responsible for the initiation of sexual maturation are unknown.

Animals↗

Modulation of cellular immunity by a lesion of the lateral hypothalamic area (LHA) in rats.

The subject of our investigation was the effect of bilateral damage to the lateral hypothalamic area (LHA) on the cellular immune response (CIR), assessed by measuring the diameter of skin infiltration (DSI) 24 and 48 h after intradermal administration of tuberculin in adult male Wistar rats, previously immunized with BCG vaccine. It has been shown that: 1) in the hypothalamo-lesioned rats (HLR) DSI measured 24 and 48 h after tuberculinization did not differ, 2) in the sham-operated rats (SOR) DSI measured 48 h after tuberculin injection was significantly higher (p < 0.02) than that found 24 h after the antigen administration, 3) the damage-induced loss of body weight and the 24-48 h difference in DSI in the responders of the HLR group correlated negatively with each other (r = -0.806, p < 0.05). These results indicate that damage to the LHA enhances the rate of formation, but not the maximal size, of the tuberculin-induced skin infiltration. Thus, the LHA seems to be involved in the regulation/modulation of processes engaged in the expression of tuberculin reaction.

Animals↗

Lateral hypothalamic area and paraventricular nucleus connections with subfornical organ neurons: an electrophysiological study in the rat.

The neural pathways from the lateral hypothalamic area (LHA) to the hypothalamic paraventricular nucleus (PVN) mediated by subfornical organ (SFO) neurons were examined in urethane-anesthetized male rats in order to determine the excitability of vasopressin (VP)-secreting neurons in the PVN. Microinjection of angiotensin II (AII) into the LHA excited the activity of nearly half (n = 8) of the SFO neurons (n = 18) activated antidromically by electrical stimulation of the PVN. Microinjection of AII into the LHA also caused excitation of approximately one-quarter (n = 11) of putative VP-secreting neurons (n = 45) in the PVN while the excitatory responses of the putative VP-secreting neurons were blocked or attenuated by pretreatment with the AII antagonist, saralasin (Sar), in the SFO. Electrical stimulation of the LHA, on the other hand, produced excitation (n = 17) or inhibition (n = 14) of the putative VP-secreting neurons (n = 52) in the PVN. About half of the excitatory responses to LHA stimulation were blocked or attenuated by pretreatment with Sar in the SFO, whereas the inhibitory responses were not affected. These results show some possible connections between the LHA and PVN, and suggest that AII-sensitive LHA neurons with efferent projections to the SFO may act to enhance the excitability of putative VP-secreting neurons in the PVN via an excitatory influence on the AII-sensitive SFO neurons.

Action Potentials↗

The descending alpha-MSHergic (alpha-melanocyte-stimulating hormone-ergic) projections from the zona incerta and lateral hypothalamic area to the inferior colliculus and spinal cord in the rat.

Neuronal pathways containing alpha-melanocyte-stimulating hormone (alpha-MSH) extending from the zona incerta and lateral hypothalamic area to the inferior colliculus and spinal cord were analyzed using both immunohistochemical localization and a retrograde tracer. Biotinized horseradish peroxidase injected into the inferior colliculus or the thoracic cord of the rat labeled a number of neurons in the zona incerta and lateral hypothalamic area. Simultaneous immunostaining of the same sections with alpha-MSH antiserum showed that some of these neurons are alpha-MSHergic.

Animals↗

[Ultrastructural changes in the neurons and interneuronal connections of the lateral hypothalamic area in rats at different times of food deprivation].

Changes in bodies of neurons, their processes and synapses in the lateral hypothalamic area (LHA) in rats at various time (1, 3, 5 and 7 days) of food deprivation have been studied electron microscopically. The changes in the posterior part of the LHA are the first and in the middle part of the LHA are the last to appear. The number of altered bodies of the neurons, their processes, synapses and severity of their injury during all the time of fasting is the greatest in the posterior and the least in the middle part of the LHA. The character of the ultrastructural changes is unitypical everywhere. Dendrites, especially those of middle and large size are the first to be injured. Their changes immediately acquire destructive character (vacuolization of dendroplasm, appearance of complex membranous bodies, swelling and destruction od microtubules and neurofilaments). One of peculiar features of the destructive changes of the neuronal processes and synapses is invagination of adjoining areas of axons and synapses into the dendrite. In the bodies of the neurons the changes appear later than in the dendrites and at first they are of functional character and only beginning from the 5th day of fasting certain signs of destructive disorders are noted. With increasing time of fasting, the injury is growing more severe and a greater and a greater number of the neuronal bodies, processes and synapses are involved into the pathological process.

Animals↗

Afferent projections related to attack sites in the ventral midbrain tegmentum of the cat.

Quiet attack was elicited by electrical stimulation of the ventrolateral midbrain tegmentum of the cat. The paw was not used other than to position or hold the rat during the bite. Bites were directed toward the head and neck region and were not accompanied by autonomic responses other than pupillary dilation and sometimes slight piloerection on the back. Horseradish peroxidase was deposited at the attack sites. Cells labeled with the peroxidase reaction product were located in gyrus propreus, gyrus genualis, nucleus accumbens, bed nucleus of the stria terminalis, bed nucleus of the anterior commissure, nucleus of the diagonal band, substantia innominata, anterior amygdaloid area, ventromedial hypothalamic area, paraventricular nucleus, perifornical hypothalamic area, lateral hypothalamic area, dorsal hypothalamic area, field of Forel, midbrain reticular formation, superior colliculus, ventral central grey, lateral central gray, locus coeruleus, parabrachial nuclei, nucleus of the lateral lemniscus, oral pontine reticular nucleus, and the dorsal raphe. Other regions were less prominently labeled. Previous studies have shown most of these sites to have some involvement in attack.

Afferent Pathways↗

Dipsogenic response induced by angiotensinergic pathways from the lateral hypothalamic area to the subfornical organ in rats.

Experimental observations in several species have suggested that angiotensinergic neural circuits from the lateral hypothalamic area (LHA) to the subfornical organ (SFO) may participate in the control of drinking behavior in the rat. In an attempt to verify this possibility, experiments were undertaken to investigate whether activation of LHA neurons following microinjection of angiotensin II (ANG II) into the LHA elicits drinking. Injections of ANG II (10(-11) mol) into the LHA caused drinking in 25 out of 36 rats having the tips of cannulas in the LHA. The efficacy of ANG II was potentiated by increasing the dose of the drug. To clarify the contribution of angiotensinergic neurons in the LHA with efferent projections to the SFO to the drinking induced by ANG II, the effects of pretreatment with saralasin (Sar), a specific ANG II antagonist, in the SFO or its surrounding region on the drinking to ANG II were examined. Previous injections of Sar into the SFO significantly reduced the water intake caused by ANG II injected into the LHA, whereas treatment with Sar in the ventral hippocampal commissure (VHC) or third ventricle (3V) was without effect. These findings provide the evidence for the involvement of the angiotensinergic pathways from the LHA to the SFO in the dipsogenic action.

Angiotensin II↗

[Effects of electrical stimulation of lateral hypothalamic area on gastric ischemia-reperfusion injury in rats].

The effects of electrical and chemical stimulation and electrolytic lesion of lateral hypothalamic area (LHA) on gastric ischemia-reperfusion injury (GI-RI) were investigated in rats whose celiac arteries were clamped for 30 min and reperfused for 60 min by removal of the clamp. The results are as follows. (1) Electrical stimulation of LHA could aggravate GI-RI in an intensity-dependent manner by using 0.2, 0.4 or 0.6 mA current respectively. Microinjection of L-glutamic acid into LHA resulted in a similar effect to that of electrical stimulation of LHA on GI-RI. After electrolytic lesion of bilateral LHA, the area of gastric mucosal injury induced by gastric ischemia-reperfusion (GI-R) was smaller than that by electrical stimulation of LHA plus GI-R. (2) Dorsal vagal complex (DVC) lesion or vagotomy could eliminate the effect of electrical stimulation of LHA on GI-RI. (3) Electrical stimulation of LHA increased the content of malondialdehyde (MDA) but decreased the activity of superoxide dismutase (SOD) of ischemia-reperfusion (I-R) gastric mucosa. (4) Electrical stimulation of LHA plus gastric I-R increased gastric juice volume and total acid output, but there were no significant changes in acidity, pepsin activity and gastric barrier mucus. These results indicate that the LHA is an area in the CNS exerting aggravate effects on GI-RI. The DVC and vagus may be involved in the regulative effects of LHA on GI-RI. These effects are associated with increases in gastric mucosal MDA content, gastric juice volume, and total acid output, and a decrease in SOD activity.Acidity, pepsin activity and gastric barrier mucus do not seem to play an important role.

Animals↗

Medullary catecholaminergic neurons projecting to lateral hypothalamic area and expressing Fos after chemical stimulation of the stomach in the rat.

Catecholaminergic neurons in the medulla projecting to lateral hypothalamic area (LH) and expressing Fos were investigated in the rat by a triple labelling method, in which horseradish peroxidase (HRP) was injected into the LH, and visceral noxious stimulation was induced by formalin injection into the stomach, sections of the medulla were stained histochemically for HRP and immunohistochemically for Fos and tyrosine hydroxylase (TH). Some neurons labeled with HRP and showing both Fos- and TH-like immunoreactivities were mainly found in the nucleus tractus solitarii (NTS) and ventrolateral medulla (VLM) at the middle and caudal levels of medulla, only a few of them were located in the reticular formation between NTS and VLM. These results indicated that some medullary catecholaminergic neurons projected to the LH and some of them might be involved in the transmissing processes of stress responses to the visceral nociceptive information produced by chemical stimulation.

Animals↗

A pharmacological analysis of autonomic pathways mediating myocardial disturbances originating in a lateral hypothalamic area of the cat.

A study was made of the mechanisms mediating autonomic changes resulting from stimulation of a site in the lateral hypothalamic area (LHA). This site, when stimulated, induced angina-like ECG disturbances similar to those observed in some cases of brain traumas. These ECG changes were often associated with other autonomic changes, such as pressor response, tachycardia (in some cases bradycardia), nictitating membrane (NM) contraction and pupillary dilatation. Most symptoms were sympathetic: they were largely abolished by spinal cord section between C1 and C2, but were not affected by vagotomy, except that bradycardia was converted to tachycardia. Adrenal catecholamines were not involved since adrenal vein ligation was without effect. Hexamethonium (5-10 mg/kg) prevented pressor response and tachycardia in most cats but only partly protected against ECG changes and NM contractions. Atropine methyl nitrate (0.2 mg/kg) abolished the remaining ECG abnormalities and NM tension. The beta-receptor antagonists, propranolol and practolol (50 micrograms/kg) completely prevented the ECG changes induced either by isoprenaline or LHA stimulation. It is concluded that the symptoms induced by LHA stimulation result from noradrenaline release in the target organs.

Angina Pectoris↗

Effects of injection of selective adrenergic receptor antagonists into the lateral hypothalamic area on renal function.

Studies were undertaken to characterize the participation of specific alpha-1,alpha-2 and beta adrenoceptors of the lateral hypothalamic area (LHA) in the urinary excretion of sodium and potassium. Alpha-1 and alpha-2 LHA receptors were shown to participate in the regulation of renal sodium and potassium excretion. The effects of noradrenaline microinjection (30 nmol in 1 microliter) into the LHA on urinary sodium excretion (UNaV) are blocked by previous injection of the alpha-1 antagonist prazosin (4 nmol in 1 microliter) from 3.22 +/- 0.25 to 0.59 +/- 0.04 microEq min-1 100 g body weight-1. Pre-injection of yohimbine, an alpha-2 antagonist (4 nmol in 1 microliter), synergistically potentiated the action of noradrenaline on UNaV (3.22 +/- 0.25 to 4.02 +/- 0.27 microEq min-1 100 g body weight-1) and on urinary potassium excretion (UKV) (0.70 +/- 0.08 to 1.15 +/- 0.12 microEq min-1 100 g body weight-1). The beta-adrenergic blockers metoprolol (100 nmol in 1 microliter) and propranolol (100 nmol in 1 microliter) had no synergistic or antagonistic action on the sodium excretion fraction, suggesting that neither of these receptors is present in LHA. Our results indicate that natriuresis occurs even in the absence of changes in glomerular filtration rate and demonstrate an inhibitory natriuretic effect of an alpha-1 blocker (prazosin) injected into the LHA before adrenaline, while an alpha-2 antagonist (yohimbine) yielded a potentiating effect.

Adrenergic alpha-Antagonists↗

Mediation of dehydration-induced peptidergic gene expression in the rat lateral hypothalamic area by forebrain afferent projections.

We have previously shown in dehydrated rats that cellular levels of the mRNAs encoding the precursor peptides for corticotropin-releasing hormone and neurotensin/neuromedin N significantly increase in a restricted region of the lateral hypothalamic area (Watts, 1992, Brain Res. 581:208-216). The experiments reported here address the role that forebrain osmosensitive cells groups or regions associated with autonomic regulation play in developing this mRNA response. The first experiment showed that unilateral knife cuts placed between the rostral forebrain and the lateral hypothalamic area (LHA) will unilaterally attenuate the mRNA response in the LHA to dehydration. In a second experiment, small injections of the retrograde tracer Fluorogold into the region of the LHA containing these mRNAs revealed a direct input from the osmosensitive median preoptic nucleus and subfornical organ and from the fusiform nucleus of the bed nuclei of the stria terminalis, which is part of a complex of cell groups associated with autonomic regulation. We found that at least 30% of the neurons in the median preoptic nucleus and subfornical organ and 14% of the neurons in the fusiform nucleus of the bed nuclei of the stria terminalis that project to the LHA responded to a rapid increase in plasma osmolality with increased c-fos mRNA levels. In the final experiment, injections of Fluorogold into the LHA were made simultaneously with ipsilateral rostral knife cuts. Here the numbers of neurons accumulating Fluorogold in the median preoptic nucleus, subfornical organ, and the fusiform nucleus were all significantly decreased concomitantly with attenuated mRNA responses in the LHA to dehydration. We conclude that the LHA receives direct and functional projections from the median preoptic nucleus, subfornical organ, and the fusiform nucleus. These projections appear capable of mediating a substantial part of the response of peptidergic mRNAs in the LHA to dehydration.

Afferent Pathways↗

Neurons in the rat lateral hypothalamic area integrate information from the gastric vagal nerves and the cerebellar interpositus nucleus.

Previous investigations have demonstrated that the neuronal activity in the lateral hypothalamic area (LHA) is respectively modulated by afferent inputs from the gastric vagal nerves innervating the upper gastrointestinal tract, as well as the cerebellar interpositus nucleus (IN). The aim of this study was to examine whether the gastric vagal and cerebellar IN inputs converge onto single LHA neurons in rats, especially those sensitive to glycemia. Of the 114 LHA neurons recorded, 60 (52.6%) and 51 (44.7%) responded to gastric vagal and cerebellar IN stimulation, respectively. Of the 60 LHA neurons responsive to gastric vagal stimulation, 30 also responded to the cerebellar IN stimulus, indicating a convergence of gastric vagal and cerebellar inputs onto single hypothalamic cells. When the gastric vagal nerves and cerebellar IN were stimulated simultaneously, a summation of the responses was observed in all 6 neurons tested. Moreover, of 24 neurons that responded to both the gastric vagal and cerebellar IN stimuli, 15 (62.5%) were identified as glycemia-sensitive. These results demonstrate that the visceral information transmitted by the gastric vagal nerves and the somatic information forwarded by the cerebellar IN converge onto single LHA neurons, especially those sensitive to glycemia. The findings also suggest that integration of somatic-visceral responses related to short-term feeding regulation may take place in the LHA.

Animals↗

Interaction between cholinergic and osmolar stimulation of the lateral hypothalamic area (LHA) on sodium and potassium excretion.

Hypotonic and isotonic solutions into the LHA of unrestrained rats caused no alteration in renal water and electrolyte excretion. Similar results were obtained after injecting hypo, iso and hypertonic glucose solutions. On the other hand, a hypertonic NaCl solution produced an increase in natriuresis and kaliuresis immediately after being injected into the LHA. The carbachol elicited an increase in natriuresis and kaliuresis as well as a decrease in urine output in the first urine samples collected after the injection being injected into the LHA. This response was not modified when the same dose of carbachol was injected associated with NaCl or glucose solutions. The observation of a lack of summation between the effects of carbachol and hypertonic NaCl, as well as the maintenance of the natriuretic and kaliuretic effects in response of the injection of the hypertonic solution even in the presence of blocked cholinergic pathways (atropine), suggests a dissociation between the mechanisms activated by the hypertonic solution and the cholinergic stimulation of the LHA.

Animals↗

Coexistence of substance P and neurotensin-like peptides in single neurons of the rat hypothalamus.

The coexistence of substance P with neurotensin-like immunoreactivity in certain neurons of the hypothalamus were demonstrated by the double immunofluorescence method. Substance P and neurotensin-like immunoreactivity coexisted within single neurons of some hypothalamic areas such as the medial preoptic area, perifornical area, anterior hypothalamic area, lateral hypothalamic area, periventricular nucleus and posterior hypothalamic nucleus, although they did not coexist in the majority of immunoreactive cells.

Animals↗