The role of the posterior hypothalamus in the regulation of paradoxical sleep

Posterior hypothalamus was found to take part in the inhibitory control of the paradoxical sleep executive mechanisms responsible for the ECoG desynchronisation and phasic events. Functional activity of the posterior hypothalamus seems to be at its lowest during the paradoxical sleep stage as characterised by phasic events and the ECoG desynchronisation, and increases during the stage with alpha-like activity in the ECoG and absence of phasic events, the latter having, probably, a "sentinel" function.     

Blood flow and pO2 in the posterior hypothalamus of cats during paradoxical sleep

In chronic experiments on cats it has been found by recording of the brain local blood flow (BLBF) and of oxygen tension (pO2) in the posterior and anterior hypothalamus, that at sleep phases alternation, the changes of these parameters are differently directed: during the paradoxical sleep the level of BLBF and pO2 oscillations frequency increased in the posterior hypothalamus and decreased in the anterior one. During slow-wave sleep opposite relations were observed. Opposite directions of changes of BLBF level and pO2 oscillations frequency in one and the same phase of sleep show that they are of local origin and must be determined by functional-metabolic shifts. In particular, the increase of BLBF level and frequency of pO2 oscillations must reflect a rise of posterior hypothalamus functional-metabolic activity during paradoxical sleep.     

The effect of leukocyte pyrogen on thermosensitive neurons of the anterior hypothalamus]

Impulse activity of neurons of the medial preoptic and septal brain areas of rabbits caused by variations in the local temperature and systemic injections of the leukocytic and bacterial pyrogens was studied. The firing rate of the warmsensitive neurons decreased and that of the cold thermodetectors was activated as a result of pyrogen action. As compared with the bacterial pyrogen, leukocytic pyrogen caused a more rapid decrease of the warmthermodetector activity. Thermoneutral neurons failed to react considerably either to the leukocytic or to the bacterial pyrogen.     

Projections of the posterior area of the hypothalamus to its medial,anterior, and lateral areas

The effect of stimulation of the lateral and medial supramammillary areas of the posterior hypothalamus on spontaneous single unit activity in the anterior, lateral, medial dorsal, and medial ventral areas of the hypothalamus was investigated in acute experiments on rabbits. Single stimulation of the medial area of the posterior hypothalamus evoked responses of 44% of neurons, whereas stimulation of the lateral area did so in only 35% of all neurons recorded. Repetitive stimulation led to an increase in the number of responding neurons (to 57% during stimulation of the lateral and 74% during stimulation of the medial supramammillary area). In response to repetitive stimulation of the medial supramammillary area, activating influences became predominant in all areas, whereas in response to stimulation of the lateral area, they became predominant in the medial, ventral, and lateral areas. The results are assessed from the standpoint of the role of the posterior hypothalamus in the regulation of adenohypophyseal functions.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 9, No. 4, pp. 377–381, July–August, 1977.     

Different neuronal phenotypes in the lateral hypothalamus and their role in sleep and wakefulness

The sleep disorder narcolepsy is now linked with a loss of neurons containing the neuropeptide hypocretin (also known as orexin). The hypocretin neurons are located exclusively in the lateral hypothalamus, a brain region that has been implicated in arousal based on observations made by von Economo during the viral encephalitic epidemic of 1916–1926. There are other neuronal phenotypes located in the lateral hypothalamus that are distinct and separate from the hypocretin neurons. Here the authors identify these neurons based on peptides and neurotransmitters that they express and review roles of these neurons in sleep. Given the heterogeneity of the neuronal phenotypes in the lateral hypothalamus, it is likely that hypocretin neurons, as well as other types of neurons in the lateral hypothalamus, influence sleep and provide state-dependent regulation of physiological functions.     

Regulation of the neuronal norepinephrine transporter by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

We previously reported that endothelin-1 and endothelin-3 modulate norepinephrine neuronal release and tyrosine hydroxylase activity and expression in the hypothalamus. In the present study we sought to establish the role of endothelin-1 and -3 in the regulation of norepinephrine uptake in the anterior and posterior hypothalamus. Results showed that in the anterior hypothalamus endothelin-3 increased neuronal norepinephrine uptake whereas endothelin-1 decreased it. Conversely, in the posterior hypothalamic region both endothelins diminished the neuronal uptake of the amine. Endothelins response was concentration dependent and maintained at all studied times. Endothelins also modified the kinetic and internalization of the NE neuronal transporter. In the anterior hypothalamic region endothelin-3 increased the V_max and the B_max whereas endothelin-1 decreased them. However, in the posterior hypothalamic region both endothelins diminished the V_max as well as B_max. Neither endothelin-1 nor endothelin-3 modified neuronal norepinephrine transporter K_d in the studied hypothalamic regions. These findings support that in the posterior hypothalamic region both endothelins diminished neuronal norepinephrine transporter activity by reducing the amine transporter expression on the plasmatic membrane. Conversely, in the anterior hypothalamic region endothelin-3 enhanced neuronal norepinephrine transporter activity by increasing the expression of the transporter on the presynaptic membrane, whereas endothelin-1 induced the opposite effect. Present results permit us to conclude that both endothelins play an important role in the regulation of norepinephrine neurotransmission at the presynaptic nerve endings in the hypothalamus.     

Regulation of the neuronal norepinephrine transporter by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

We previously reported that endothelin-1 and endothelin-3 modulate norepinephrine neuronal release and tyrosine hydroxylase activity and expression in the hypothalamus. In the present study we sought to establish the role of endothelin-1 and -3 in the regulation of norepinephrine uptake in the anterior and posterior hypothalamus. Results showed that in the anterior hypothalamus endothelin-3 increased neuronal norepinephrine uptake whereas endothelin-1 decreased it. Conversely, in the posterior hypothalamic region both endothelins diminished the neuronal uptake of the amine. Endothelins response was concentration dependent and maintained at all studied times. Endothelins also modified the kinetic and internalization of the NE neuronal transporter. In the anterior hypothalamic region endothelin-3 increased the V_max and the B_max whereas endothelin-1 decreased them. However, in the posterior hypothalamic region both endothelins diminished the V_max as well as B_max. Neither endothelin-1 nor endothelin-3 modified neuronal norepinephrine transporter K_d in the studied hypothalamic regions. These findings support that in the posterior hypothalamic region both endothelins diminished neuronal norepinephrine transporter activity by reducing the amine transporter expression on the plasmatic membrane. Conversely, in the anterior hypothalamic region endothelin-3 enhanced neuronal norepinephrine transporter activity by increasing the expression of the transporter on the presynaptic membrane, whereas endothelin-1 induced the opposite effect. Present results permit us to conclude that both endothelins play an important role in the regulation of norepinephrine neurotransmission at the presynaptic nerve endings in the hypothalamus.     

Unit responses in the anterior and posterior hypothalamus to stimulation of the splanchnic and sciatic nerves and to photic stimulation

By extracellular recording of spike discharges the sensory properties of neurons of the anterior and posterior regions of the cat hypothalamus were studied during stimulation of the splanchnic and sciatic nerves and during photic stimulation. Hypothalamic neurons were shown to be characterized by wide convergence of heterosensory excitation: 68% of spontaneously active hypothalamic neurons responded to somatovisceral and photic stimulation. Some posterior hypothalamic neurons responded to somatovisceral stimulation but not to photic stimulation. Neurons responding only to photic stimulation were found in the anterior hypothalamus; no neurons responding only to visceral stimulation were found in the hypothalamus. Total convergence of somatic and visceral afferentation of neurons of the posterior and anterior hypothalamus was observed. Mostly responses of phasic type were obtained to stimulation of all modalities. The study of the quantitative ratio between responses of excitatory and inhibitory types showed that the former predominate. The principles governing the functional organization of hypothalamic afferent systems are discussed.Academician L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 8, No. 3, pp. 276–282, May–June, 1976.     

The ventromedial nucleus of the hypothalamus and the hormonal arousal of sexual behaviors in the female rat

Bilateral lesions of the ventromedial nucleus of the hypothalamus interfered with the estrogenic induction of sexual receptivity in the female rat, but seemingly did not affect the ability of female rats to show lordosis following combined stimulation with estrogen and progesterone. In addition, ventromedial hypothalamic lesions did not affect the ability of females to show male-like sexual activity in response to exogenous androgenic stimulation.     

Role of the lateral hypothalamus in sleep

Sleep and Biological Rhythms -     

Increase of paradoxical sleep, induced by injection of ibotenic acid in the ventrolateral posterior hypothalamus in the cat

The intratissular injection of ibotenic acid into the ventrolateral part of the posterior hypothalamus induced a dramatic biphasic and transient hypersomnia immediately after disappearance of the anaesthesia (14 to 24 hrs. after injection). The duration of hypersomnia was related to the dose of neurotoxin injected. Its first period was characterized by an increase in paradoxical sleep (PS) (300%). Then, during the second phase, PS disappeared and there was a subsequent increase of slow wave sleep (SWS) (60%). Finally, on the third day, all cats recovered control level of PS and SWS.     

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ET(B) receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ET(C) receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.