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.     

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.     

Effects of microinjections of triazolam into the ventrolateral preoptic area on sleep in the rat

In view of interest in the ventrolateral preoptic area (VLPO), based on FOS protein accumulation during sleep as well as its output pathways to areas involved in sleep regulation, we have examined the effects of microinjections of triazolam into the VLPO. It was found that two doses of triazolam, noted previously to enhance sleep when injected into the medial preoptic area, had no significant effect on sleep or core temperature when administered into the VLPO. Although these data do not bear on the possibility that the VLPO is involved in physiological sleep regulation, they suggest that it is not a site of the pharmacologic action of hypnotic benzodiazepines.     

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.     

Interdependence of learning and paradoxical sleep in the cat

The effect of learning sessions on the structure of the sleep-wakefulness cycle, as well as the effect of paradoxical sleep (PS) deprivation (PSD) following learning sessions, on the acquisition and extinction of instrumental alimentary reflexes to two feeders with sound discrimination, were studied on cats. The analysis of the data obtained led to following conclusions: The above learning sessions have no marked effect on the structure of the sleep-wakefulness cycle in the post-learning period, i.e. the percentage ratio of its phases is not altered by the increase of one of them. When PSD by non-emotional awakening is used, the number of PS onsets is not affected by learning sessions. This indicates that learning does not produce any considerable effect on the formation of PS need. PSD by non-emotional awakening following learning sessions does not retard the acquisition and extinction of the instrumental alimentary reflexes. The above data are interpreted as indicating that PS has no specific significance in memory trace consolidation during formation of long-term memory.     

Increase in duration of paradoxical sleep after carotid occlusion in rats

Nonlinear rats, which survived after occlusion of one or two common carotid arteries (N = 30, about 30% survived) were examined. Sham-operated animals formed a control group. In animals with ischemia, the total sleep duration in a three-hour period was substantially increased as compared to control group at the expense of a substantial growth (8-9 times) of paradoxical sleep (PS) phase. In the animals with ischemia, a sharp increase in PS was observed on the first postoperation day, and then PS gradually decreased from the first to the fortieth days. The results suggest the PS involvement in the brain intrinsic reparation functions.     

Changes in cat behavior as affected by intracerebral microinjections of kynurenine and quinolinic acid

Behavioural changes induced by microinjections of neuroactive tryptophan metabolites: L-kynurenine sulfate (KYN, 50-1,000 micrograms) and quinolinic acid (QA, 20-1,000 micrograms) were studied in chronic experiments on cats with cannulas implanted into nuclei caudati. Unlike KYN, whose effects were scarce and nonspecific, QA (500 and 1,000 micrograms) produced marked motor and emotional shifts. The effects were manifested in contralateral rotatory movements, limb hyperkinesis, emotional strain, malice, fear, aggression with snarling and hissing, attack on provocation. It is suggested that kynurenines and QA can participate in the generation of emotional disorders peculiar for epilepsy.     

Spatiotemporal characteristics of evoked potentials in the posterior ventrolateral nucleus of the cat thalamus

Evoked potentials (EPs) in the posterior ventrolateral nucleus (VPL) of the thalamus in response to electrical stimulation of the skin of the contralateral forelimb were studied. It was shown that they are formed by superposition of several electrical dipoles, one of which lies with two poles in VPL while the rest have one pole in VPL and the other in more caudal zones of the somatosensory system. The first phase of the EP in VPL consists of two components with different amplitude—frequency characteristics. The lability of the second component is low and it disappears if the frequency of stimulation rises above 20 Hz. The focus of maximal activity during contralateral stimulation of the skin of the forelimb occupies the same topographical position in VPL during development of the positive and negative phases of the EP. The steepness of rise of the ascending phase and the amplitude of the positive phase of the EP are greatest at the focus of maximal activity; in other regions the lines of equal steepness need not necessarily coincide with the equipotential lines; differences are especially noticeable in the sagittal plane.Institute of the Brain, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 4, No. 4, pp. 439–446, July–August, 1972.     

Attenuation of aortic baroreflex responses by microinjections of endomorphin-2 into the rostral ventrolateral medullary pressor area of the rat

The presence of mu-opioid receptors and endomorphins has been demonstrated in the general area encompassing the rostral ventrolateral medullary pressor area (RVLM). This investigation was carried out to test the hypothesis that endomorphins in the RVLM may have a modulatory role in regulating cardiovascular function. Blood pressure and heart rate (HR) were recorded in urethane-anesthetized male Wistar rats. Unilateral microinjections of endomorphin-2 (0.0125-0.5 mmol/l) into the RVLM elicited decreases in mean arterial pressure (16-30 mmHg) and HR (12-36 beats/min), which lasted for 2-4 min. Bradycardia was not vagally mediated. The effects of endomorphin-2 were mediated via mu-opioid receptors because prior microinjections of naloxonazine (1 mmol/l) abolished these responses; the blocking effect of naloxonazine lasted for 15-20 min. Unilateral stimulations of aortic nerve for 30 s (at frequencies of 5, 10, and 25 pulses/s; each pulse 0.5 V and 1-ms duration) elicited depressor and bradycardic responses. These responses were significantly attenuated by microinjections of endomorphin-2 (0.2 and 0.4 mmol/l). The inhibitory effect of endomorphin-2 on baroreflex responses was prevented by prior microinjections of naloxonazine. Microinjections of naloxonazine alone did not affect either baseline blood pressure and HR or baroreflex responses. These results indicate that endomorphin-2 elicits depressor and bradycardic responses and inhibits baroreflex function when injected into the RVLM. These effects are consistent with the known hyperpolarizing effect of opioid peptides on RVLM neurons.     

Feeding induced by opiates injected into the paraventricular hypothalamus

Injection of morphine or d-ala-2-met-5-enkephalinamide (DALA) into the paraventricular nucleus of the hypothalamus (PVN) produced a dose dependent increase in feeding in rats. DALA increased feeding within 45 minutes; morphine within 90 minutes. Naloxone injected into the PVN diminished the effect. DALA increased water intake only when food was available, suggesting the primary effect was on feeding. In summary, an enkephalin analogue induced feeding, and an opiate receptor blocker attenuated it; therefore the PVN may contain opiate receptors that facilitate feeding.     

Mapping of cholinoceptive brainstem structures responsible for the generation of paradoxical sleep in the cat

In order to determine the cholinoceptive brainstem structures critical for PS generation, we investigated the effect on PS induction of the injection of a small dose and volume (0.4 microgram/0.2 microliter) of the cholinergic agonist carbachol in the following caudal brainstem structures: 1) the caudal mesencephalic reticular formation, especially the nucleus pedunculopontinus pars compacta or X area; 2) the mediodorsal pontine tegmentum, in particular the nuclei locus coeruleus (LC), locus coeruleus alpha (LC alpha), peri-locus coeruleus alpha (peri-LC alpha) and laterodorsalis tegmenti (Ldt); 3) the pontine; and 4) bulbar gigantocellular (FTG) and magnocellular tegmental fields (FTM). We found that the only brainstem area from which a high amount of PS was induced by carbachol applications with short latencies, less than 5 minutes, is the mediodorsal pontine tegumentum, namely the LC alpha and peri-LC alpha, where ChAT-and TH- immunoreactive neurons are intermingled. Injections in an area immediately ventral to the peri-LC alpha induced physiological states resembling PS but lacking certain electrophysiological (PS-like) and behavioral components of PS (dissociated states I and II). The weak PS induction following carbachol administration in the anteromedial part of the FTG was due to the spread of the drug toward the efficient site since the latencies to PS onset were in the range of 20 to 60 minutes. No effects on PS generation were obtained after carbachol microinjections in the LC and the laterocaudal part of the FTG, while carbachol injections in the X area or in the bulbar FTG or FTM resulted in the increase of waking and the decrease of PS. In addition to these effects on PS induction, we also found that carbachol induced: 1) stereotyped PGO-like bursts when injected in the ventral part of the FTG and the rostral part of the FTM, 2) postural atonia with very short latencies, less than two minutes, when injected in the LC alpha and peri-LC alpha; and 3) hippocampal theta waves of 3-5 Hz persisting during light slow wave sleep (S1) when injected in and around the LC alpha and peri-LC alpha and in some points of the mediocaudal part of the FTG. These results support the hypothesis that PS is generated by highly localized neuronal populations and suggest that the mediodorsal pontine tegmentum (namely the nuclei LC alpha and peri-LC alpha) may represent a cholinoceptive PS generator.     

Obesity induced by kainic acid microlesion in the ventromedial hypothalamus in rats

The neurotoxin kainic acid was injected bilaterally into the ventromedial hypothalamus of female rats in doses of 100 or 200 ng. The injections produced microlesions which led to progressive body weight gain and fat deposition in dose dependent manner. The histological examination revealed that the lesions were mainly located in the region between the ventromedial hypothalamic nuclei and the fornix.