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[The effect of the lateral hypothalamic area on the pulmonary surfactant system].

The level of lipids, lipase activity and lungs' blood capacity were studied on 62 rats. Dispersal cobalt was infused into the hypothalamic lateral area of rats with adrenalectomy or injected with droperidol, obsidan, reserpine. Their effect upon the hypothalamus involved a decrease in surfactant phospholipids and lung's blood capacity. Possible adrenergic mechanisms of affecting the lung surfactant system are discussed.

Adrenalectomy↗

Efferent connections from the lateral hypothalamic region and the lateral preoptic area to the hypothalamic paraventricular nucleus of the rat.

The lateral preoptic and lateral hypothalamic regions contain the majority of the cell groups embedded in the fibre trajectories of the medial forebrain bundle on its course through the hypothalamus. Recent studies have extended considerably the parcellation of the lateral hypothalamic region, and therefore, the need to emphasize new insights into the anatomical organisation of projections from the neurons of the lateral hypothalamic region. In the present study we describe the anatomical organisation of efferent projections from the lateral preoptic and lateral hypothalamic regions to the hypothalamic paraventricular nucleus (PVN) on the basis of retrograde- and anterograde-tracing techniques. Iontophoretic injections of the retrograde tracer, cholera toxin subunit B, into the PVN revealed that most hypothalamic nuclei project to the PVN. Within the lateral hypothalamic region, retrogradely labelled cells were concentrated in the intermediate hypothalamic area, the lateral hypothalamic area, and the perifornical nucleus, whereas fewer retrogradely labelled cells were found in the lateral preoptic area. To determine the distribution of terminating fibres in subnuclei of the heterogeneous PVN, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were delivered into distinct areas of the lateral hypothalamic region. Neurons of the intermediate hypothalamic area projected mainly to the PVN subnuclei, which contained parvicellular neuroendocrine cells. In contrast, neurons of the rostral and tuberal parts of the lateral hypothalamic area and the perifornical nucleus projected to the PVN subnuclei, which contained parvicellular neurons that send descending projections to preganglionic cell groups in the medulla and spinal cord. The perifornical nucleus was the only area within the lateral hypothalamic region that consistently innervated magnocellular perikarya of the PVN. Finally, all areas of the lateral hypothalamic region contributed substantially to fibres terminating in the perinuclear shell of the PVN. These results demonstrate that anatomically distinct areas of the lateral hypothalamic region have distinct projections to subnuclei of the PVN and further substantiate the view that the lateral hypothalamic region as well as the PVN constitute anatomically and functionally heterogeneous structures.

Animals↗

Sleep-waking discharge patterns of neurons recorded in the rat perifornical lateral hypothalamic area.

The perifornical lateral hypothalamic area (PF-LHA) has been implicated in the control of several waking behaviours, including feeding, motor activity and arousal. Several cell types are located in the PF-LHA, including projection neurons that contain the hypocretin peptides (also known as orexins). Recent findings suggest that hypocretin neurons are involved in sleep-wake regulation. Loss of hypocretin neurons in the human disorder narcolepsy is associated with excessive somnolence, cataplexy and increased propensity for rapid eye movement (REM) sleep. However, the relationship of PF-LHA neuronal activity to different arousal states is unknown. We recorded neuronal activity in the PF-LHA of rats during natural sleep and waking. Neuronal discharge rates were calculated during active waking (waking accompanied by movement), quiet waking, non-REM sleep and REM sleep. Fifty-six of 106 neurons (53 %) were classified as wake/REM-related. These neurons exhibited peak discharge rates during waking and REM sleep and reduced discharge rates during non-REM sleep. Wake-related neurons (38 %) exhibited reduced discharge rates during both non-REM and REM sleep when compared to that during waking. Wake-related neurons exhibited significantly higher discharge rates during active waking than during quiet waking. The discharge of wake-related neurons was positively correlated with muscle activity across all sleep-waking states. Recording sites were located within the hypocretin-immunoreactive neuronal field of the PF-LHA. Although the neurotransmitter phenotype of recorded cells was not determined, the prevalence of neurons with wake-related discharge patterns is consistent with the hypothesis that the PF-LHA participates in the regulation of arousal, muscle activity and sleep-waking states.

Action Potentials↗

Effects of ibotenic acid-induced neuronal degeneration in the medial preoptic area and the lateral hypothalamic area on sexual behavior in the male rat.

It is well known that electrolytic lesions in the medial preoptic area (MPOA) and the lateral hypothalamic area (LHA) seriously impair masculine sexual behavior in the rat. We here report that bilateral infusions of the neurotoxin, ibotenic acid (IBO), in the MPOA were as effective as electrolytic lesions in eliminating copulation whereas no behavioral effects were detected following similar infusions in the LHA. Histological examination of MPOA and LHA following IBO exposure revealed extensive degeneration of neuronal cell bodies with little evidence of non-specific damage. Also, immunohistochemical studies suggested that the serotonergic innervation of the MPOA remained largely intact in spite of IBO treatment; similarly, the damage inflicted by IBO in LHA on tyrosine hydroxylase-immunoreactive fibers in the medial forebrain bundle was insignificant. These data suggest that: (i) the functional integrity of MPOA nerve cell bodies is necessary for the expression of sexual behavior, and (ii) disruption of mating produced by electrolytic LHA lesions is due to disruption of medial forebrain bundle fiber systems. Behavioral observations of non-copulating males suggested that the MPOA injury did not interfere with all aspects of their sexual interaction with the estrous female; rather, they appeared specifically unable to perform the reflexive pelvic thrust pattern normally associated with mounting. We here report, however, that the ability to perform mounts with pelvic thrusts was temporarily restored in the vast majority of MPOA-injured males by the i.p. administration of the ergot derivative, lisuride. About 50% of these MPOA-damaged males even ejaculated, often after a low number of intromissions and short ejaculation latencies. On the other hand, injections of naloxone (an opiate receptor antagonist) failed to activate mounting in MPOA-lesioned or castrated rats. On the basis of these findings the possible ways in which steroid hormone-sensitive brain areas might interact with monoamine-containing pathways are discussed.U

Animals↗

Neurons in the lateral hypothalamic area and zona incerta with ascending projections to the subfornical organ area in the rat.

Sixteen neurons in the lateral hypothalamic area (LH) and 12 neurons in the zona incerta (ZI) were antidromically activated by electrical stimulation of the subfornical organ (SFO) area in urethane-anesthetized male rats. The activity of these LH and ZI units was examined for response to intracarotid injections of isotonic (0.15 M NaCl solution, 0.05 ml) or hypertonic (0.18 M or 0.3 M NaCl solution, 0.05 ml) saline. All the units did not change their activity to the injections of isotonic saline. Of these units, 9 LH and 5 ZI units displayed an increase and 2 LH and 3 ZI units exhibited a reduction in neuronal activity following the injections of hypertonic saline, while the remaining 5 LH and 3 ZI units were unresponsive. The present results suggest that the LH and ZI neurons with ascending projections to the SFO may carry the information from osmoreceptive elements for modulating the actions of the SFO.

Afferent Pathways↗

The substrate for brain-stimulation reward in the lateral preoptic area: III. Connections to the lateral hypothalamic area.

Double-pulse tests were used to estimate the refractory periods and anatomical linkage of the reward-relevant fibers that course between the lateral preoptic and lateral hypothalamic areas. In the 1st study, pairs of conditioning and test pulses were delivered to each site, and the interval between pulses varied; recovery from refractoriness was similar at both sites, with the curves generally rising from 0.6 to 2.0 ms. In the 2nd study, the pairs of pulses were delivered to both sites. Six of 7 rats showed evidence of axonal collision, with estimates of conduction velocity that ranged from 0.48 to 8.95 m/s across rats. These results suggest that a wide spectrum of fiber types characterizes the reward-relevant axons that course uninterruptedly between these 2 regions.

Action Potentials↗

Inhibition of gastric acid secretion by cholinergic stimulation of the lateral hypothalamic area.

Cholinergic stimulation of the lateral hypothalamic area with carbachol (1 microgram in 1 microliter) markedly inhibited gastric acid secretion in the anesthetized rat. Inhibition was blocked by prior micro-injection of atropine (4 micrograms/microliters) into the same brain area and was accompanied by an increased sodium content in the stomach. Muscarinic receptor mediated cholinergic inhibitory influence of the hypothalamus on gastric acid secretion is suggested by these results.

Animals↗

Lateral hypothalamic area stimulation excites neurons in the region of the subfornical organ with efferent projections to the hypothalamic paraventricular nucleus in the rat.

Fifteen neurons in the region of the subfornical organ (SFO) were antidromically activated by electrical stimulation of the paraventricular nucleus (PVN) in the rat. Electrical stimulation of the lateral hypothalamic area (LHA) excited the activity of 9 of the identified units, but did not affect the remaining units. The excitatory response of the identified units was blocked by microiontophoretically (MIPh) applied saralasin (Sar), an angiotensin II (ANGII) antagonist, but not by atropine (Atr), a muscarinic antagonist. These results suggest that the LHA has an excitatory influence on the activity of neurons in the region of the SFO with efferent projections to the PVN and that the influence may be mediated by ANGII receptors.

Angiotensin II↗

Lesions in lateral hypothalamic areas increase splenocyte apoptosis.

OBJECTIVE: The lateral hypothalamic area (LHa) is involved in various functions such as feeding, drinking, sexual and reward behavior, among others. Recently, we demonstrated that the LHa can regulate cellular immunity in the spleen. In experiments involving the LHa, it was noticed that the spleen shrinks noticeably after LHa destruction. To explore this phenomenon further, the effect of LHa lesioning on splenocyte apoptosis was investigated. METHODS: Male Wistar-King-Aptekman rats underwent bilateral lesioning of their LHa and consequent spleen weights, splenocyte numbers and apoptosis were measured. For the detection of splenocyte apoptosis, both ELISA, which measures DNA fragmentation within the splenocytes, and flow cytometry, which measures the percentage of apoptotic lymphocytes in the spleen, were used. RESULTS: In the LHa-lesioned rats, spleen weights and the number of splenocytes decreased significantly within 24 h. Additionally, in the spleen, lymphocyte apoptosis significantly increased compared to the control after 6 h. CONCLUSION: These results suggest that the LHa may play a role in immunoregulation by affecting lymphocytes in the spleen through apoptosis and may be relevant to the pathway of stress-induced apoptosis.

Animals↗

Neurotensin in the lateral hypothalamic area: origin and function.

The origin of neurotensin in the lateral hypothalamus was investigated by means of fluorescent retrograde tract tracing and neurotensin-like immunoreactivity. Following fluorescent retrograde tract tracing with FluoroGold combined with neurotensin immunohistochemistry in the rat brain, numerous neurotensin-immunoreactive neurons with projections to the posterior lateral hypothalamic area were identified in the central nucleus of the amygdala, perifornical area and the parabrachial nucleus. Fewer numbers of neurotensin-positive neurons with projections to the lateral hypothalamic area were observed in the bed nucleus of the stria terminalis, lateral septal nucleus, medial preoptic area, peri- and paraventricular nuclei of the hypothalamus, anterior lateral hypothalamic area and dorsal raphe nucleus. In addition, the role of neurotensin in the modulation of autonomic regulatory input from the insula was investigated. The lateral hypothalamic area was surveyed for single units responding to electrical stimulation (500-900 microA, 0.5 Hz) of sites in the insular cortex from which cardiovascular pressor or depressor responses could be elicited. These units were tested for the influence of neurotensin on responses to stimulation of the insular cortex. Of 60 spontaneously firing neurons, 27 units responded to electrical stimulation of cardiovascular sites in the insula. Of the units responding to stimulation of cardiovascular sites in the insula, 14 units showed excitation only, 10 units showed excitation followed by inhibition and three units showed inhibition. Iontophoresis of 0.1-1.0 mM neurotensin (25-100 nA, pH 5.0-6.0) potentiated six of the excitatory responses and showed no effect on the inhibitory responses. In addition, nine neurons showed an increase in spontaneous activity with iontophoresis of neurotensin. Of these neurons, three were excited by insular stimulation and six did not respond. These findings indicate the likely origin of neurotensin in the lateral hypothalamic area and demonstrate that neurotensin has a role in the modulation of some of the cardiovascular regulatory input from the insular cortex.

Amygdala↗

Effects of electrical stimulation of the central nucleus of the amygdala and the lateral hypothalamic area on the oval nucleus of the bed nuclei of the stria terminalis and its adjacent areas in the rat.

Our recent studies demonstrated that there are reciprocal connections between the oval nucleus (Ov) of the bed nuclei of the stria terminalis (BST) and the central nucleus of the amygdala (Ce) or the lateral hypothalamic area (LHA). The present experiments found that spontaneous unit discharges of 73 neurons in the Ov and its adjacent areas were modified in 58 neurons (79.45%) by focal brain stimulation in the Ce. After focal LHA stimulation, the spontaneous unit discharges of 23 (53.49%) of 43 Ov neurons, which could be influenced by focal Ce stimulation, were changed. Thirteen Ov neurons were antidromically activated by focal Ce or LHA stimulation. These results indicate that: (1) neuronal activities in the Ov and its adjacent areas can be modulated by Ce or LHA; (2) there are functional reciprocal connections between Ov and Ce or LHA; and (3) the Ce and LHA afferents converge upon some Ov neurons.

Action Potentials↗

RNA content of neurons in the ventromedial nuclei and lateral hypothalamic area relative to feeding status.

The total RNA content of hypothalamic and cortex neurons in relation to the feeding status of adult male Wistar rats was studied. Experimental conditions including food deprivation (12 and 24 hours) and relative satiation (short-term refeeding, glucose or glycerol administration) changed in different ways the total RNA content of the neurons in the ventromedial hypothalamic nuclei (VMH) and in the lateral hypothalamic area (LHA) with respect to fasting or satiety. Only the long-term absence of food (24 hours) significantly increased the total RNA content of the VMH cells, while the RNA content of the LHA neurons significantly decreased in both the 12 and 24 hr fasted rats compared with those fed ad lib. The sixty minute free access to food after 12 or 24 hours of fasting fully reversed these changes. The short-term food intake significantly increased the RNA content of the LHA cells of the 12 and 24 hr fasted animals while the total RNA content of the VMH neurons significantly decreased only in the 24 hr fasted rats. The effect of glucose and glycerol administration on the RNA content of the LHA neurons (in 12 hr fasted rats) was similar to the effect of refeeding. One hour after giving glucose (1 g/kg b.wt.) or glycerol (300 mg/kg b.wt.) the total RNA content in the LHA neurons significantly increased. No changes in RNA content were observed in the neurons of the cortex when comparing the experimental and control rats. The results demonstrated the close relationship between the RNA content of the hypothalamic neurons and the feeding status.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modifications of the electrical activity in the ventromedial hypothalamic nucleus and the lateral hypothalamic area of 24-hour food-deprived rats.

The amplitude of the electrical activity of the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LH) was evaluated in rats after 24-hr food deprivation to determine the effects of the diet they had received before fasting. Bioelectrical potentials were registered by means of monopolar electrodes. In rats after 24-hr food deprivation an increase in the absolute values of the amplitude of the electrical activity of the VMH and LH was found; this effect was more pronounced in the LH. Comparing the amplitude of the electrical activity of the VMH and LH, we found it to be always higher in the VMH in ad libitum fed rats, while in 24-hr food-deprived rats the electrical activity was always higher in the LH. The extent of changes depended on the diet the rats had received before fasting--they were most marked in rats fed on a high-protein diet and less marked in rats fed on either a standard or a high-fat diet before food deprivation.

Animals↗

Adaptation in patterns of c-fos expression in the brain associated with exposure to either single or repeated social stress in male rats.

Intraspecific confrontation between male rats represents a biologically relevant form of social stress. C-fos expression has been used to map the pattern of neural activation following either a single (acute) or repeated (10 times) exposure of an intruder male to a larger male in the latter's home cage. These conditions induce high levels of aggressive interaction. Sixty minutes after a single defeat, there was intense c-fos expression (quantified using image analysis) in restricted areas of the basal forebrain (including lateral septum, bed nucleus of stria terminalis, lateral preoptic area, lateral hypothalamic area, paraventricular nucleus, and medial and central amygdala) as well as in the autonomic and monoaminergic nuclei of the brainstem (central grey, dorsal and median raphe, locus coeruleus and nucleus of the solitary tract). After the tenth defeat, this pattern was modified despite persistently high levels of aggression. Some areas in the forebrain (bed nucleus of stria terminalis, paraventricular nucleus and medial amygdala) continued to express increased c-fos; others (the septum, lateral hypothalamic area, lateral preoptic area and central amygdala) no longer expressed c-fos. The brainstem response was equally varied: the central grey and the raphe nuclei continued to respond after repeated defeat, whereas the solitary nucleus and locus coeruleus did not. On the other hand, there was no change in the behaviour of intruder rats after repeated defeat. This study shows the pattern of adaptation at a cellular level in the basal forebrain and brainstem to repeated defeat. As in our previous studies of repeated restraint, modulation in the expression of c-fos following repeated stress is highly regionally specific, suggesting that differential neural processing is involved in adaptation to social stress.

Adaptation, Psychological↗

Identification of retinal ganglion cells projecting to the lateral hypothalamic area of the rat.

The objective of the present study was to identify the retinal ganglion cells projecting to the lateral hypothalamic area of the rat. The retinohypothalamic tract has been divided into a medial and a lateral component on anatomical and developmental grounds. The medial component projects to the suprachiasmatic nucleus and adjacent structures such as the anterior hypothalamic and retrochiasmatic areas. The lateral component terminates in the lateral hypothalamic are dorsal to the supraoptic nucleus. Injections of the retrograde tracer FluoroGold were made into the retinorecipient region of the lateral hypothalamic area and retinal whole mounts were immunohistochemically processed for retrogradely labeled retinal ganglion cells. With FluoroGold injections confined to the lateral hypothalamic area, retrogradely labeled retinal ganglion cells are located almost exclusively in the superior temporal quadrant of the retina. Their size and morphology indicates that they are a homogeneous subset of type III cells, but a definitive classification would require a more complete fill of dendritic arbors than is available in our retrograde material. In contrast, injections involving fibers of passage in the optic tract, or centered in the medial terminal nucleus of the accessory optic system, label cells distributed across the entire retinal surface. Unlike the retinal ganglion cells projecting to the suprachiasmatic nucleus [Moore et al., J. Comp. Neurol., 352 (1995) 351-366], the cells labeled after restricted lateral hypothalamic injections are not distributed evenly across the retinal surface. The difference in location of the retinal ganglion cells projecting to the lateral hypothalamic area supports the view that this retinohypothalamic projection is anatomically and functionally distinct from the projection to the suprachiasmatic nucleus and adjacent medial hypothalamus.

Animals↗

The lateral hypothalamic area revisited: ingestive behavior.

This article discusses the role of the lateral hypothalamic area (LHA) in feeding and drinking and draws on data obtained from lesion and stimulation studies and neurochemical and electrophysiological manipulations of the area. The LHA is involved in catecholaminergic and serotonergic feeding systems and plays a role in circadian feeding, sex differences in feeding and spontaneous activity. This article discusses the LHA regarding dietary self-selection, responses to high-protein diets, amino acid imbalances, liquid and cafeteria diets, placentophagia, "stress eating," finickiness, diet texture, consistency and taste, aversion learning, olfaction and the effects of post-operative period manipulations by hormonal and other means. Glucose-sensitive neurons have been identified in the LHA and their manipulation by insulin and 2-deoxy-D-glucose is discussed. The effects on feeding of numerous transmitters, hormones and appetite depressants are described, as is the role of the LHA in salivation, lacrimation, gastric motility and secretion, and sensorimotor deficits. The LHA is also illuminated as regards temperature and feeding, circumventricular organs and thirst and electrolyte dynamics. A discussion of its role in the ischymetric hypothesis as an integrative Gestalt concept concludes the review.

Animals↗

An autoradiographic study of the efferent connections of the lateral hypothalamic area in the rat.

The efferent connections of the lateral hypothalamic area (LHA) have been analyzed in a series of 30 rat brains with injections of 3H-amino acids into different parts of the area and the surrounding regions. Our findings indicate that all parts of the LHA contribute ascending and descending fibers to the medial forebrain bundle, and also project medially to certain of the adjoining hypothalamic nuclei. All levels of the LHA appear to send some fibers to a continuous group of structures that extends from the medial septal-diagonal band complex rostrally, through the lateral preoptic and lateral hypothalamic areas to the mammillary complex and the ventral tegmental area caudally. In addition, it is evident that cells at different levels within the LHA may have differential projections. Thus, the anterior and lateral parts of the LHA also appear to project substantially to the anterior hypothalamic area, the ventromedial and dorsomedial hypothalamic nuclei, the parataenial and paraventricular nuclei of the thalamus, and the medial part of the lateral habenular nucleus. Similarly, cells in the tuberal and posterior parts of the LHA project to the central gray, the longest projections from the posterior region reaching as far caudally as the central tegmental field, the parabrachial nucleus, the locus coeruleus, and the superior central and dorsal nuclei of the raphe. Viewed as a whole, the LHA is therefore well-suited to integrate inputs from the limbic system and brainstem and to relay them on the one hand to the medial zone of the hypothalamus and on the other to virtually every structure closely associated with the medial forebrain bundle and to the nuclei of origin of the major ascending monoaminergic systems.

Animals↗

Increased neuropeptide Y concentrations in the lateral hypothalamic area of the rat after the onset of darkness: possible relevance to the circadian periodicity of feeding behavior.

Neuropeptide Y (NPY) is a major hypothalamic peptide which powerfully stimulates feeding when injected into the hypothalamus and is implicated in circadian rhythmicity. To investigate whether NPY is involved in the increased feeding that follows the onset of darkness in rats, NPY levels were measured in discrete hypothalamic areas before and after darkness. Four groups of eight adult female Wistar rats were habituated to a 12:12 hour light:dark cycle, with food presented at the onset of darkness (19.00 hours). One group was sacrificed during the 3 hours before darkness and another in the first 2.5 hours after darkness, with food provided as usual. To distinguish any effects of feeding itself, the study was repeated with two further groups, but food was not provided after darkness. Seven hypothalamic regions were microdissected from slices of fresh brain and acid-extracted for radioimmunoassay of NPY. NPY levels (fmol/microgram protein) were significantly higher (p less than 0.01) in the lateral hypothalamic area (LHA) of the dark-phase group in both studies. In the other six regions, NPY levels did not differ between light and dark phases. The LHA regulates the circadian rhythmicity of feeding and NPY injection here stimulates feeding. Alterations in NPY in the LHA around the onset of darkness may be related to the initiation of dark-phase feeding.

Animals↗