Dorsolateral Hypothalamus Research Articles

The role of lateral hypothalamic nucleus in mediating locomotive behaviors in pigeons (Columba livia)

The lateral hypothalamic nucleus (LHy) is located in the dorsolateral hypothalamus of birds, and it is essential to many life processes. However, limited information is available about the role of LHy in mediating locomotive behaviors. In this work, we investigated the structure and function of LHy in pigeons (Columba livia) by Nissl staining, immunohistochemical (IHC) staining, insituhybridization (ISH) staining and constant current stimulation methods. The results showed that LHy appears crescent in shape, and three-dimensional coordinate value range of LHy is: A: 5.0–8.0 mm, L: 0.7–1.2 mm, D: 9.5–10.3 mm. The dopaminergic neurons in LHy were distributed in small amount and concentrated manner, while the glutamatergic neurons were distributed in a large number and uniform manner. The distribution of the above two neurons at each coronal level showed a significant positive correlation (R2 = 0.7516, P < 0.001). Our work demonstrated that LHy mainly mediates forward movement (P < 0.01) and ipsilateral lateral movement (P < 0.001), and these movements were significantly effected by electrical stimulation intensity. Our results showed that LHy can mediate the generation of directional behavior and this will provide technical support for the study of locomotor behavior regulation in birds.

Prolactin-Releasing Peptide Contributes to Stress-Related Mood Disorders and Inhibits Sleep/Mood Regulatory Melanin-Concentrating Hormone Neurons in Rats.

Stress disorders impair sleep and quality of life; however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator; we therefore hypothesized that PrRP may be involved in the development of stress disorders. PrRP is produced by the medullary A1/A2 noradrenaline (NA) cells, which transmit stress signals to forebrain centers, and by non-NA cells in the hypothalamic dorsomedial nucleus. We found in male rats that both PrRP and PrRP-NA cells innervate melanin-concentrating hormone (MCH) producing neurons in the dorsolateral hypothalamus (DLH). These cells serve as a key hub for regulating sleep and affective states. Ex vivo, PrRP hyperpolarized MCH neurons and further increased the hyperpolarization caused by NA. Following sleep deprivation, intracerebroventricular PrRP injection reduced the number of REM sleep-active MCH cells. PrRP expression in the dorsomedial nucleus was upregulated by sleep deprivation, while downregulated by REM sleep rebound. Both in learned helplessness paradigm and after peripheral inflammation, impaired coping with sustained stress was associated with (1) overactivation of PrRP cells, (2) PrRP protein and receptor depletion in the DLH, and (3) dysregulation of MCH expression. Exposure to stress in the PrRP-insensitive period led to increased passive coping with stress. Normal PrRP signaling, therefore, seems to protect animals against stress-related disorders. PrRP signaling in the DLH is an important component of the PrRP's action, which may be mediated by MCH neurons. Moreover, PrRP receptors were downregulated in the DLH of human suicidal victims. As stress-related mental disorders are the leading cause of suicide, our findings may have particular translational relevance.SIGNIFICANCE STATEMENT Treatment resistance to monoaminergic antidepressants is a major problem. Neuropeptides that modulate the central monoaminergic signaling are promising targets for developing alternative therapeutic strategies. We found that stress-responsive prolactin-releasing peptide (PrRP) cells innervated melanin-concentrating hormone (MCH) neurons that are crucial in the regulation of sleep and mood. PrRP inhibited MCH cell activity and enhanced the inhibitory effect evoked by noradrenaline, a classic monoamine, on MCH neurons. We observed that impaired PrRP signaling led to failure in coping with chronic/repeated stress and was associated with altered MCH expression. We found alterations of the PrRP system also in suicidal human subjects. PrRP dysfunction may underlie stress disorders, and fine-tuning MCH activity by PrRP may be an important part of the mechanism.

Core Body Temperature Varies According to the Time of Exercise Without Affecting Orexin-A Production in the Dorsolateral Hypothalamus in Rat

Core Body Temperature Varies According to the Time of Exercise Without Affecting Orexin-A Production in the Dorsolateral Hypothalamus in Rat

Hypothalamus and amygdala functional connectivity at rest in narcolepsy type 1

Introductionfunctional and structural MRI studies suggest that the orexin (hypocretin) deficiency in the dorso-lateral hypothalamus of narcoleptic patients would influence both brain metabolism and perfusion and would cause reduction in cortical grey matter. Previous fMRI studies have mainly focused on cerebral functioning during emotional processing. The aim of the present study was to explore the hemodynamic behaviour of spontaneous BOLD fluctuation at rest in patients with Narcolepsy type 1 (NT1) close to disease onset. MethodsFifteen drug naïve children/adolescents with NT1 (9 males; mean age 11.7 ± 3 years) and fifteen healthy children/adolescents (9 males; mean age 12.4 ± 2.8 years) participated in an EEG-fMRI study in order to investigate the resting-state functional connectivity of hypothalamus and amygdala. Functional images were acquired on a 3 T system. Seed-based functional connectivity analyses were performed using SPM12. Regions of Interest were the lateral hypothalamus and the amygdala. Resultscompared to controls, NT1 patients showed decreased functional connectivity between the lateral hypothalamus and the left superior parietal lobule, the hippocampus and the parahippocampal gyrus. Decreased functional connectivity was detected between the amygdala and the post-central gyrus and several occipital regions, whereas it was increased between the amygdala and the inferior frontal gyrus, claustrum, insula, and putamen. Conclusionin NT1 patients the abnormal connectivity between the hypothalamus and brain regions involved in memory consolidation during sleep, such as the hippocampus, may be linked to the loss of orexin containing neurons in the dorsolateral hypothalamus. Moreover, also functional connectivity of the amygdala seems to be influenced by the loss of orexin-containing neurons. Therefore, we can hypothesize that dysfunctional interactions between regions subserving the maintenance of arousal, memory and emotional processing may contribute to the main symptom of narcolepsy.

The Melanin-Concentrating Hormone (MCH) System: A Tale of Two Peptides.

The melanin-concentrating hormone (MCH) system is a robust integrator of exogenous and endogenous information, modulating arousal and energy balance in mammals. Its predominant function in teleosts, however, is to concentrate melanin in the scales, contributing to the adaptive color change observed in several teleost species. These contrasting functions resulted from a gene duplication that occurred after the teleost divergence, which resulted in the generation of two MCH-coding genes in this clade, which acquired distinctive sequences, distribution, and functions, examined in detail here. We also describe the distribution of MCH immunoreactivity and gene expression in a large number of species, in an attempt to identify its core elements. While initially originated as a periventricular peptide, with an intimate relationship with the third ventricle, multiple events of lateral migration occurred during evolution, making the ventrolateral and dorsolateral hypothalamus the predominant sites of MCH in teleosts and mammals, respectively. Substantial differences between species can be identified, likely reflecting differences in habitat and behavior. This observation aligns well with the idea that MCH is a major integrator of internal and external information, ensuring an appropriate response to ensure the organism’s homeostasis. New studies on the MCH system in species that have not yet been investigated will help us understand more precisely how these habitat changes are connected to the hypothalamic neurochemical circuits, paving the way to new intervention strategies that may be used with pharmacological purposes.

Role of Orexin-A in Hypertension and Obesity.

Hypertension is one of the most challenging health problems inducing cerebrovascular disease and high percentage of death when associated with diabetes, dyslipidemias, and obesity. Orexin/hypocretin is a peptide expressed by a small number of neurons of the dorsolateral hypothalamus, a brain feeding and autonomic "fight-or-flight" regulatory center. According to this function, orexin has been demonstrated to evoke cardiovascular responses, heart rate, hypertension, hyperarousal, hyperphagia, and obesity. The focus of this review is to provide an overview about the mechanism through which orexin regulates food intake and cardiovascular responses and its role in the pathogenesis of obesity and hypertension which could be of great interest to establish possible new therapies. In normal rats and mice, central administration of orexin increases food intake, blood pressure, and sympathetic nerve activity and these effects are blocked by selective orexin receptor antagonist SB-334867 or almorexant. Moreover, upregulation of orexin signaling, in combination with elevation of epinephrine and norepinephrine circulating levels, occurs in rats exposed to chronic stress, in models of spontaneous hypertension (SHR and BPH/2J Schlager mice) and in obese mice (ob/ob or mice fed with high fat diet). Therefore, hyperactivity of orexinergic neurons could be a factor in the development of obesity and essential hypertension. Because of their widespread projections to the brain regions involved in appetite and cardiovascular responses, as far down as sympathetic preganglionic neurons in the spinal cord, orexin evokes sympathetically mediated cardiovascular responses. Lasting upregulation of orexin signaling can lead to hyperphagia, obesity, and hypertensive state. Dual orexin receptor antagonists (DORAs) and selective orexin receptor antagonists (SORAs) have antihypertensive effects that could be of clinical use for regulation of food intake and hypertension, supporting the role of orexinergic neurons as critical checkpoint in the neurogenic control of metabolic and cardiovascular functions.

Motivational activation: a unifying hypothesis of orexin/hypocretin function.

Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system.

Neurobiologic Mechanisms of Sleep and Wakefulness

Neurobiologic Mechanisms of Sleep and Wakefulness

Cellular location and major terminal networks of the orexinergic system in the brain of two megachiropterans

The present study describes the distribution of orexin-A immunoreactive neurons and their terminal networks in the brains of two species of megachiropterans. In general the organization of the orexinergic system in the mammalian brain is conserved across species, but as one of two groups of mammals that fly and have a high metabolic rate, it was of interest to determine whether there were any specific differences in the organization of this system in the megachiropterans. Orexinergic neurons were limited in distribution to the hypothalamus, and formed three distinct clusters, or nuclei, a main cluster with a perifornical location, a zona incerta cluster in the dorsolateral hypothalamus and an optic tract cluster in the ventrolateral hypothalamus. The nuclear parcellation of the orexinergic system in the megachiropterans is similar to that seen in many mammals, but differs from the microchiropterans where the optic tract cluster is absent. The terminal networks of the orexinergic neurons in the megachiropterans was similar to that seen in a range of mammalian species, with significant terminal networks being found in the hypothalamus, cholinergic pedunculopontine and laterodorsal tegemental nuclei, the noradrenergic locus coeruleus complex, all serotonergic nuclei, the paraventricular nuclei of the epithalamus and adjacent to the habenular nuclei. While the megachiropteran orexinergic system is typically mammalian in form, it does differ from that reported for microchiropterans, and thus provides an additional neural character arguing for independent evolution of these two chiropteran suborders.

Interactions between orexin–immunoreactive fibers and adrenaline or noradrenaline-expressing neurons of the lower brainstem in rats and mice

Orexins are expressed in neurons of the dorsolateral hypothalamus and their axons widely distribute throughout the central nervous system. The noradrenergic cell groups of the lower brainstem belong to the targets of these orexin projections. Double immunostainings for orexin and phenylethanolamine N-methyltransferase (PNMT), as well as orexin and tyrosine hydroxylase (TH) were applied to demonstrate the orexinergic innervation of catecholamine cell groups in the lower brainstem of the mouse and the rat. In various densities, networks of orexin-positive fibers and terminals were present on neurons of each adrenaline (C1, C2, C3) and noradrenaline (locus coeruleus, A1, A2, A4, A5 and A7) cell groups. The most dense networks of orexin fibers and terminals were detected in the locus coeruleus, the subcoeruleus area, and in the nucleus of the solitary tract. By using confocal microscope to analyze triple immunostainings we could detect that about two-third of the orexin-PNMT or orexin-TH immunopositive close contacts contained synaptophysin (a presynapse-specific protein) in the C1, C2 and C3 adrenaline, or in the A1, A2 noradrenaline cell groups, respectively. Orexin–immunopositive axons in the C1, C2, as well as A1, A2 and A6 cell groups have been examined by an electron microscope. Relatively few asymmetrical (excitatory) synaptic contacts could be demonstrated between PNMT- or TH-positive dendrites and orexin terminals, although the vast majority of orexin-positive axons was located in juxtaposition to PNMT- or TH-positive neurons.

Orexin/Hypocretin and Histamine: Distinct Roles in the Control of Wakefulness Demonstrated Using Knock-Out Mouse Models

To determine the respective role played by orexin/hypocretin and histamine (HA) neurons in maintaining wakefulness (W), we characterized the behavioral and sleep-wake phenotypes of orexin (Ox) knock-out (-/-) mice and compared them with those of histidine-decarboxylase (HDC, HA-synthesizing enzyme)-/- mice. While both mouse strains displayed sleep fragmentation and increased paradoxical sleep (PS), they presented a number of marked differences: (1) the PS increase in HDC(-/-) mice was seen during lightness, whereas that in Ox(-/-) mice occurred during darkness; (2) contrary to HDC(-/-), Ox(-/-) mice had no W deficiency around lights-off, nor an abnormal EEG and responded to a new environment with increased W; (3) only Ox(-/-), but not HDC(-/-) mice, displayed narcolepsy and deficient W when faced with motor challenge. Thus, when placed on a wheel, wild-type (WT), but not littermate Ox(-/-) mice, voluntarily spent their time in turning it and as a result, remained highly awake; this was accompanied by dense c-fos expression in many areas of their brains, including Ox neurons in the dorsolateral hypothalamus. The W and motor deficiency of Ox(-/-) mice was due to the absence of Ox because intraventricular dosing of orexin-A restored their W amount and motor performance whereas SB-334867 (Ox1-receptor antagonist, i.p.) impaired W and locomotion of WT mice during the test. These data indicate that Ox, but not HA, promotes W through enhanced locomotion and suggest that HA and Ox neurons exert a distinct, but complementary and synergistic control of W: the neuropeptide being more involved in its behavioral aspects, whereas the amine is mainly responsible for its qualitative cognitive aspects and cortical EEG activation.

Narcolepsia con y sin cataplejia: una enfermedad rara, limitante e infradiagnosticada

Although narcolepsy is a relatively uncommon condition, its impact on a child's life can be dramatic and disabling. Narcolepsy is characterized by excessive daytime sleepiness (EDS), with brief "sleep attacks" at very unusual times and usually associated with cataplexy (sudden loss of muscle control while awake, resulting in a fall, triggered by laughter). Other symptoms frequently reported are sleep paralysis (feeling of being unable to move or speak, even totally aware), hypnagogic hallucinations (vivid dreamlike experiences difficult to distinguish from reality) or disturbed night time sleep. Some children also experience depression or overweight-obesity. Although narcolepsy has been thoroughly studied, the exact cause is unknown. It appears to be a disorder of cerebral pathways that control sleep and wakefulness, involving dorsolateral hypothalamus and hypocretin. A genetic factor has been suggested, but narcolepsy in relatives is rare. Researchers have suggested that a set of genes combines with additional factors in a person's life to cause narcolepsy. The effective treatment of narcolepsy requires not only medication (usually stimulants, antidepressants and sodium oxybate), but also adjustments in life-style (scheduled naps). Management of this condition in children demands a comprehensive approach to the patient, that includes a correct diagnosis, pharmacological and non-pharmacological treatment and adjustments in the environment. These strategies can improve the child's self-esteem and ability to obtain a good education.

Spatial and temporal activation of brain regions in hibernation: c‐fos expression during the hibernation bout in thirteen‐lined ground squirrel

Hibernation results in dramatic changes in body temperature and metabolism; however, the central nervous system remains active during deep torpor. By cloning c-fos cDNA from the 13-lined ground squirrel (Spermophilus tridecemlineatus) and using squirrel c-fos mRNA probe for in situ hybridization histochemistry, we systematically analyzed and identified specific brain regions that were activated during six different phases of the hibernation bout. During entrance into torpor, we detected activation of the ventrolateral subdivision of the medial preoptic area ('thermoregulatory center'), and the reticular thalamic nucleus, which is known to inhibit the somatomotor cortex. During torpor, c-fos expression in the cortex was suppressed while the reticular thalamic nucleus remained uniformly active. Throughout torpor the suprachiasmatic nucleus ('biological clock') showed increasing activity, likely participating in phase-change regulation of the hibernation bout. Interestingly, during torpor very strong c-fos activation was seen in the epithelial cells of the choroid plexus and in tanycytes at the third ventricle, both peaking near the beginning of arousal. In arousal, activity of the suprachiasmatic and reticular thalamic nuclei and choroid epithelial cells diminished, while ependymal cells in the lateral and fourth ventricles showed stronger activity. Increasing body temperature during arousal was driven by the activation of neurons in the medial part of the preoptic area. In interbout awake animals, we demonstrated the activation of hypothalamic neurons located in the arcuate nucleus and the dorsolateral hypothalamus, areas involved in food intake. Our observations indicate that the hibernation bout is closely regulated and orchestrated by specific regions of the central nervous system. J. Comp. Neurol. 505:443-458, 2007. (c) 2007 Wiley-Liss, Inc.

Sleep deprivation increases the activation of nuclear factor kappa B in lateral hypothalamic cells

Sleep deprivation increases sleep propensity in rats and mice as well as the production of several sleep-regulatory substances. Nuclear factor kappa B (NF-κB) is a transcription factor implicated in the activation of many of these sleep-promoting substances. A unique population of neurons immunoreactive for the p65 subunit of NF-κB was previously localized within the caudal dorsolateral hypothalamus of rats. Therefore, we evaluated the effect of sleep deprivation on NF-κBp65-immunoreactivity (IR) in cells of this region in rats as well as its nuclear translocation in a κB- lacZ transgenic mouse line. In rats after 6 h of sleep deprivation beginning at light onset, the number of neurons with NF-κBp65-IR increased significantly in the caudal lateral hypothalamus, specifically the magnocellular lateral hypothalamus adjacent to the subthalamus. Sleep deprivation also significantly increased the number of cells expressing NF-κB-dependent β-galactosidase in the magnocellular lateral hypothalamus, zona incerta dorsal, as well as the adjacent subthalamus in the transgenic mice. These results suggest that NF-κB expressing cells within the lateral hypothalamus may be important in the maintenance of the sleep–wake cycle.

Cocaine and amphetamine-regulated transcript mRNA regulation in the hypothalamus in lean and obese rodents.

Cocaine and amphetamine-regulated transcript (CART) mRNA and immunoreactivity are expressed abundantly in the hypothalamus. Central administration of various fragments of this neuropeptide decreases food intake in rodents. To find out whether CART might play a role in the physiological regulation of energy balance, we used in situ hybridization to investigate whether CART mRNA abundance changed in two chronic obese/fat versus lean states and after acute dietary restriction. In the first study, mice were treated with goldthioglucose to destroy glucose-responsive neurones in the ventromedial hypothalamus. This produced hyperphagia and obesity: 7 weeks after treatment, those receiving goldthioglucose weighed 70% more than the controls. CART mRNA abundance in the arcuate nucleus of goldthioglucose-treated mice was decreased by 71% compared to levels in the control mice, but CART expression was unaffected in the dorsolateral hypothalamus. In the second study, male Siberian hamsters were exposed to short days to induce a physiological winter response in which body weight decreases as fat reserves are catabolized, and food intake correspondingly declines. After 8 weeks in short days, body weight had declined by 18% relative to controls maintained in long days in a summer fat state. CART mRNA levels did not differ significantly between the two groups in any hypothalamic areas. In the third study, male Siberian hamsters, either in long days or after 12 weeks exposure to short days to induce weight loss, were subject to a 48-h period of fasting. Although photoperiod per se did not affect CART expression, fasting produced a significant decrease in CART mRNA in the arcuate nucleus of hamsters in both the long- and short-day state. We conclude that CART-producing cells are involved in energy homeostasis: the marked decrease in CART expression in the arcuate nucleus in goldthioglucose-lesioned mice may contribute to the development of obesity, and the decrease following acute dietary restriction in hamsters may reflect a compensatory mechanism to reduce caloric expenditure, but our results do not indicate that CART is involved in long-term seasonal regulation of body weight.

The hypocretins: setting the arousal threshold.

Over a short period in the late 1990s, three groups converged on the discovery of a neuropeptide system, centred in the dorsolateral hypothalamus, that regulates arousal states, influences feeding and is implicated in the sleep disorder narcolepsy. Subsequent studies have illuminated many aspects of the circuitry of the hypocretin (also called orexin) system, which also influences hormone secretion and autonomic homeostasis, and have led to the hypothesis that most human narcolepsies result from an autoimmune attack against the hypocretin-producing neurons. The biochemical, physiological and anatomical components that regulate the switch between waking and sleeping are becoming clear. The rapidity with which the hypocretin story has emerged is a testament to both the conceptual and the technical evolution of genomic science in the past two decades.

Orexins/hypocretins: waking up the scientific world.

Orexins/hypocretins: waking up the scientific world.

Origin of the serotonergic innervation to the rat dorsolateral hypothalamus: retrograde transport of cholera toxin and upregulation of tryptophan hydroxylase mRNA expression following selective nerve terminals lesion.

The regulation of serotonin synthesis was investigated in the serotonergic neurons, which provide afferents to the dorsolateral hypothalamus (DLH). The origin of the DLH projection neurons within the raphe nucleus was identified by retrograde transport of Cholera toxin (CTb) and their serotonergic nature confirmed by tryptophan hydroxylase (TPH) immunocytochemistry. Disruption of serotonin synthesis steady-state was induced unilaterally by a selective and local destruction of serotonergic nerve terminals with 5,7-dihydroxytryptamine (5,7-DHT), stereotaxically injected in the right DLH. The results show that most of the serotonergic dorsal raphe neurons projecting to the DLH have an ipsilateral localization within the lateral aspects of the nucleus. In rats with unilateral DLH lesion, a population of serotonergic cells within the raphe nucleus exhibited a clear increase in TPH mRNA. These cells were about five times more numerous in the ipsilateral as compared to the contralateral dorsal raphe nucleus and they had, for the most part, a lateral localization within the raphe nucleus. Sham-operated rats did not exhibit any upregulation of TPH mRNA. Together, the present results provide the first demonstration that a discreet and selective destruction of serotonergic terminals induces a circumscribed and striking increase in TPH mRNA expression in a subset of brainstem serotonergic neurons projecting to and/or passing through the DLH. On the basis of these results and previous in vivo measurements of TPH activity (e.g., 5-HT synthesis), we suggest that this upregulation in TPH mRNA expression results from the loss of pre-synaptic and/or post-synaptic regulation of serotonin synthesis. These new findings raise important issues related to the repercussions of a local disruption in serotonergic neurotransmission on brain areas remote from the site of injury.

Functional Relationship between the Hypothalamic Vigilance Area and PAG Vigilance Area

Duan, Y.-F., R. W. Winters, P. M. M cCabe, E. J. Green, Y. Huang and N. Schneiderman. Functional relationship between the hypothalamic vigilance area and PAG vigilance area. Physiol Behav 62(3) 675–679, 1997.—The vigilance reaction is characterized by a large bradycardia, a pressor response, and inspiratory apnea in anesthetized rabbits and the inhibition of movement in conscious rabbits. This affective response pattern can be elicited by electrical stimulation of the dorsolateral hypothalamus (the hypothalamic vigilance area) or the ventrolateral periaqueductal gray (the periaqueductal gray vigilance area). The present study sought to advance our understanding of the functional relationship between the hypothalamic vigilance area (HVA) and the periaqueductal gray vigilance area (PVA) by measuring the effects of transverse transections of the caudal portion of the ventrolateral PAG (vlPAG) upon the cardiovascular responses elicited from the dorsolateral hypothalamus and the rostral vlPAG. Selective transverse transections of the caudal vlPAG significantly reduced the magnitudes of the bradycardia and pressor response elicited by stimulation of the PVA rostral to the transection site, but had minimal impact on the cardiovascular responses evoked by stimulation of the HVA. These findings suggest that the cardiovascular responses elicited by stimulation of the vlPAG are mediated by a neural pathway that is parallel, at least in part, to the one that subserves the response elicited from the HVA. The results also provide support for the view that the PAG is not an essential structure in the mediation of the autonomic components of affective behaviors involving behavioral inhibition.

Distribution of melanin-concentrating hormone (MCH)-like immunoreactivity in neurons of the diencephalon of sheep

An immunohistochemical study with an antiserum raised salmon melanin concentrating-hormone has demonstrated the presence of numerous melanin concentrating-hormone-immunoreactive neurons in the lateral hypothalamic areas of the sheep. The pattern of distribution of these perikarya is similar to that of rodents and primates. In sheep, however, melanin concentrating-hormone-immunoreactive neurons appeared to form two gatherings: the first is situated ventromedially to the internal capsule and the second in the dorsolateral hypothalamus. In these areas, numerous immunostained perikarya are observed. Compared to the rats, labelled neurons extended more caudally in the ventral tegmental area and more rostrally above the optic chiasma. Compared to primates, these neurons are less numerous in the periventricular area. In our study, dense networks of melanin concentrating-hormone-immunoreactive varicose fibers were observed in the supramamillary nucleus, the lateral hypothalamus, the nucleus medialis thalami and nucleus reuniens andin the bed nucleus of the stria terminalis.