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Biomedical subjects

M Jouvet

Publications and source records attributed to M Jouvet.

At least 55 records · Page 3Linked to original sources

VIP-like immunoreactive projections from the dorsal raphe and caudal linear raphe nuclei to the bed nucleus of the stria terminalis demonstrated by a double immunohistochemical method in the rat.

To localize the vasoactive intestinal polypeptide (VIP)-like immunoreactive neurons at the origin of the plexuses of VIP-immunoreactive fibers found in the bed nucleus of the stria terminalis (BNST), we combined iontophoretic injections of the retrograde tracer cholera toxin B-subunit (CTb) with VIP immunocytochemistry. Following CTb injections in the BNST, 2 groups of retrogradely labeled neurons immunoreactive to VIP were detected: (1) a dorso-caudal group localized in the dorsal part of the dorsal raphe nucleus and the adjacent ventro-lateral part of the periaqueductal gray; and (2) a rostral group in the caudal linear raphe nucleus. No double-labeled cells were observed in other nuclei including those of the amygdala and the supramammillary nucleus.

Animals↗

Awakening properties of modafinil without paradoxical sleep rebound: comparative study with amphetamine in the rat.

We have studied the effect of modafinil and amphetamine, two waking drugs, on the sleep-wake cycle of Sprague-Dawley rat. Both modafinil (64 or 128 mg/kg) and amphetamine (2.5 or 5 mg/kg) cause a dose dependent increase in wakefulness. However, amphetamine wakefulness is followed by a paradoxical sleep rebound on the injection day, whereas modafinil does not produce this effect. In modafinil-treated rats, the sleep pattern on the post-injection day is similar to that of controls, while that of amphetamine-treated rats is modified.

Amphetamine↗

Suppression of Ottoson waves in the isolated olfactory bulb during sleep in the pontine cat.

In the chronic pontine cat, in which the olfactory bulbs are isolated from the brain stem, the Ottoson and/or Adrian-induced waves are suppressed during paradoxical sleep. This phenomenon cannot be explained by a central centrifugal control. The suppression of olfactory electrical activity was found to correlate with vasodilatation of the nasal mucosa. It is likely, therefore that control of the olfactory bulb activity might be mediated through the vasomotor innervation of the nasal mucosa originating from the medulla.

Animals↗

Selective suppression of type B monoamine oxidase immunoreactivity in the raphe nuclei following MPTP administration in the cat.

Using immunohistochemistry, we investigated in the cat the effects of MPTP, a Parkinsonian syndrome-inducing substance, on brain type B monoamine oxidase (MAO-B) which is responsible for the conversion of MPTP to its neurotoxic product (MPP+). Intraperitoneal administration of MPTP (5 mg kg-1 daily for 5 days) caused a selective suppression of MAO-B in neurones of the raphe nuclei without affecting hypothalamic MAO-B. Since these effects were accompanied by loss of nigral dopaminergic cells but not of raphe cell bodies or 5-HT immunoreactivity, we suggest that MPTP suppresses raphe MAO-B without destroying its presumed host serotoninergic neurones and that raphe MAO-B does not appear to be crucial in the MPTP-induced nigral lesion. In addition, the MPTP-induced paradoxical sleep suppression might be related to this raphe MAO-B loss.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and Phaseolus vulgaris leucoagglutinin.

The aim of this study was to examine the afferents to the rat locus coeruleus by means of retrograde and anterograde tracing experiments using cholera-toxin B subunit and phaseolus leucoagglutinin. To obtain reliable injections of cholera-toxin B in the locus coeruleus, electrophysiological recordings were made through glass micropipettes containing the tracer and the noradrenergic neurons of the locus coeruleus were identified by their characteristic discharge properties. After iontophoretic injections of cholera-toxin B into the nuclear core of the locus coeruleus, we observed a substantial number of retrogradely labeled cells in the lateral paragigantocellular nucleus and the dorsomedial rostral medulla (ventromedial prepositus hypoglossi and dorsal paragigantocellular nuclei) as previously described. We also saw a substantial number of retrogradely labeled neurons in (1) the preoptic area dorsal to the supraoptic nucleus, (2) areas of the posterior hypothalamus, (3) the Kölliker-Fuse nucleus, (4) mesencephalic reticular formation. Fewer labeled cells were also observed in other regions including the hypothalamic paraventricular nucleus, dorsal raphe nucleus, median raphe nucleus, dorsal part of the periaqueductal gray, the area of the noradrenergic A5 group, the lateral parabrachial nucleus and the caudoventrolateral reticular nucleus. No or only occasional cells were found in the cortex, the central nucleus of the amygdala, the lateral part of the bed nucleus of the stria terminalis, the vestibular nuclei, the nucleus of the solitary tract or the spinal cord, structures which were previously reported as inputs to the locus coeruleus. Control injections of cholera-toxin B were made in areas surrounding the locus coeruleus, including (1) Barrington's nucleus, (2) the mesencephalic trigeminal nucleus, (3) a previously undefined area immediately rostral to the locus coeruleus and medial to the mesencephalic trigeminal nucleus that we named the peri-mesencephalic trigeminal nucleus, and (4) the medial vestibular nucleus lateral to the caudal tip of the locus coeruleus. These injections yielded patterns of retrograde labeling that differed from one another and also from that obtained with cholera-toxin B injection sites in the locus coeruleus. These results indicate that the area surrounding the locus coeruleus is divided into individual nuclei with distinct afferents. These results were confirmed and extended with anterograde transport of cholera-toxin B or phaseolus leucoagglutinin. Injections of these tracers in the lateral paragigantocellular nucleus, preoptic area dorsal to the supraoptic nucleus, the ventrolateral part of the periaqueductal gray, the Kölliker-Fuse nucleus yielded a substantial to large number of labeled fibers in the nuclear core of the locus coeruleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

[3H]Nisoxetine binding sites in the cat brain: an autoradiographic study.

The binding of [3H]nisoxetine, a selective inhibitor of the high-affinity noradrenaline uptake sites, was studied on frontal frozen sections of the cat brain. The highest densities in autoradiographic signal were observed in the nucleus locus coeruleus and its ascending pathways, in the area postrema and in the dorsal part of the inferior olive, the pontine nuclei, the raphe nuclei, the colliculi, the periventricular and lateral areas of the hypothalamus, the suprachiasmatic nucleus, the nucleus accumbens and the olfactory bulb. A moderately high concentration of binding sites was observed in the hippocampal formation, especially in the molecular layer of Ammon's horn, in the superficial layers of the entorhinal cortex and in the indusium griseum. Binding sites were visualized in all the subdivisions of the neocortex. The highest density of binding was generally detected in the outer edge of the superficial layer I. In some cortical areas, especially in the visual cortex, labeling with a prevalent laminar distribution in the superficial layers I-III and in the deep layers V-VI was clearly observed. Moderate to low densities of binding sites were seen in most other areas of the brain except in the white matter, the caudate nucleus and putamen, which were devoid of labeling. Overall these findings indicate a good correlation between the distribution of [3H]nisoxetine binding sites and the noradrenergic systems. Furthermore, data suggest that in several areas, high-affinity noradrenaline reuptake mechanisms could play an important role in local interactions between the noradrenergic system and the other monoaminergic systems.

Animals↗

Effect of decerebration on blood pressure during paradoxical sleep in cats.

We investigated the effects of decerebration on long-term variations in arterial blood pressure during paradoxical sleep (PS) in cats. In normal cats, the blood pressure decreased during the transition from slow wave sleep to PS and maintained its lower level throughout PS for several days after surgery. After this early postoperative stage, however, the arterial hypotension was replaced by tonic and phasic rises in blood pressure during PS. Such long-term changes in blood pressure were completely abolished when the brain stem was transected at the ponto-mesencephalic junction, and the cats consistently exhibited a sustained fall in blood pressure throughout the survival periods of 1 month or more.

Animals↗

In vivo electrochemical monitoring of serotonin in spinal dorsal horn with Nafion-coated multi-carbon fiber electrodes.

Biosensors sensitive for in vivo monitoring of serotonin (5-HT) in the CNS by differential normal pulse voltammetry were constructed by coating treated multicarbon fiber electrodes (mCFEs) with Nafion (N-mCFE). In vitro sensitivities of mCFE and N-mCFE were compared in solutions ranging from 5 nM to 20 microM of uric acid (UA), 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT. The mCFEs were three to seven times less sensitive for 5-HIAA or UA than for 5-HT. Nafion treatment dramatically decreased sensitivity for 5-HIAA and UA of N-mCFEs (approximately 10(3) times), whereas it remained in the nanomolar range for 5-HT. In vivo, in the dorsal horn of the lumbar spinal cord of anesthetized rats, the monoamine oxidase inhibitor clorgyline (10 mg/kg i.p.) produced a reduction (55 +/- 3% at 180 min) of peak 3 of oxidation current (characteristic of 5-hydroxyindoles) monitored with mCFEs, but with N-mCFEs (in this latter case the peak was termed 3N) peak 3N increased to 135 +/- 5% at 180 min. The 5-HT release-inducer p-chloroamphetamine (PCA; 6 mg/kg i.p.) induced a slight (12 +/- 3% at 150 min) decrease in peak 3 measured with mCFEs, whereas with N-mCFEs PCA induced a rapid increase of peak 3N (137 +/- 6% at 90 min). The xanthine oxidase inhibitor allopurinol (10 mg/kg i.p.) produced a decrease (30 +/- 3% at 180 min) in peak 3 (mCFEs), but peak 3N (N-mCFEs) was not affected (106% at 180 min). After pretreatment with allopurinol, PCA also produced an increase (135 +/- 6% at 90 min) in peak 3N.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗

Corpus spongiosum penis pressure and perineal muscle activity during reflexive erections in the rat.

This experiment represents the first simultaneous analysis of corpus spongiosum of the penis (CSP) pressure and perineal muscle activity during reflex-induced penile erections in the awake rat and provides new data on the coordination of muscular and vascular events in erection physiology. Nine male Sprague-Dawley rats were implanted with pressure transducers under pentobarbital anesthesia (60 mg/kg) for use in a new technique of chronic erection recording involving simultaneous CSP pressure monitoring and electromyography (EMG) of the ischiocavernosus (IC) and bulbospongiosus (BS) muscles. The association of these physiological measurements with visually scored ex copula erectile events was investigated. Reflexive erectile events were systematically associated with an increase in baseline CSP pressure. Glans erections were associated with dramatic suprasystolic CSP pressure peaks concurrent with BS muscle bursts. Indeed, measures of CSP pressure and BS EMG activity were found to vary significantly with the intensity of glans erection. Flips of the penile body, however, involved small CSP pressure increases and IC bursts. These data demonstrate for the first time that both CSP pressures and perineal muscle activity vary significantly with the intensity of penile erection.

Animals↗

[Is there a bulbar pacemaker responsible for the ultradian rhythm of paradoxical sleep?].

Since there are complex regulations of paradoxical sleep at the supra-pontine level, the chronic pontine preparation appears to be the best model for studying the mechanisms of the ultradian rhythm of PS (tau'). In these preparations, which are ectothermic, tau' is considerably dependent upon temperature conditions. a) PS never occurs above a central temperature (Tc) of 36 degrees C which constitutes the absolute threshold for PS. b) If Tc is regulated at a plateau between 34.5 degrees C and 35.5 degrees C, the duration of tau' corresponds to about 60 min (circhoral) whereas the duration of PS is 5 min, thus the cyclic ratio: tau'/duration of PS is 12. During deep hypothermia (from 35 degrees C to 25 degrees C), tau' of PS is temperature-compensated. It remains close to 60 min, so that its Q10 is about 1. c) However, in the same conditions, the duration of PS episodes increases from 5 min to 55 min, so that the Q10 of PS is 0.1 (8% at 35 degrees C - 80% at 25 degrees C). These data are discussed in the light of the present theories explaining tau' (i.e., the reciprocal inhibition between monoaminergic permissive systems and cholinergic executive systems). An increase in PS during hypothermia might be possible provided that it should be proved that permissive mechanisms are excited by heat while executive mechanisms would be cold-sensitive. But there are no data on this point. However, even this "differential thermosensitivity hypothesis" would not explain the striking fixity of tau' between 35 degrees C and 25 degrees C. For this reason, one should hypothetize that there is a temperature-compensated oscillator or pacemaker which would act upon both executive and permissive mechanisms. This oscillator would also be controlled by metabolic factors as shown by the effect of O2 and prolactin.

Activity Cycles↗

Eye saccade dynamics during paradoxical sleep in the cat.

Cat eye movements were recorded during wakefulness and paradoxical sleep with the technique of the scleral search coil in a magnetic field. During waking, eye movements consisted of a succession of saccades and fixation phases. During paradoxical sleep, the pattern of eye movements displayed drifts of variable velocity and direction and short fixation phases, upon which saccades superimposed. These saccades displayed a repetitive, stereotyped, asymmetrical pattern. The maximum velocity/amplitude relationships, i.e. the main sequences, were determined for spontaneous and visually induced saccades of waking and for the following types of saccades during paradoxical sleep: (i) isolated saccades accompanied by ponto-geniculo-occipital (PGO) waves, (ii) isolated saccades accompanied by eye movement potentials (EMP), and (iii) saccades in bursts accompanied by PGO waves. The slope of the main sequence relationship of any type of paradoxical sleep saccade (from 21.7 degrees/s/degree for isolated saccades to 35.6 degrees/s/degree for saccades in bursts) was higher than that of any type of waking saccade (11.2 degrees/s/degree for spontaneous saccades to 14.7 degrees/s/degree for visually elicited ones). Furthermore, during paradoxical sleep, saccades in bursts were faster than isolated ones. This demonstrates that different neurophysiological mechanisms subserve the generation of waking saccades, paradoxical sleep isolated saccades and paradoxical sleep saccades in bursts, or that the oculomotor system is in a different state of excitation during these different sets of saccades. These findings throw new light on the functioning of the oculomotor system during paradoxical sleep and are discussed in terms of the functional significance of paradoxical sleep saccades and PGO waves.

Animals↗

Chronic hypoxia affects peripheral and central vasoactive intestinal peptide-like immunoreactivity in the rat.

The influence of long-term hypoxia on vasoactive intestinal peptide-like immunoreactivity (VIP-LI) in discrete brain areas and peripheral structures was assessed by RIA. Rats were exposed to normobaric hypoxia (10% O2-90% N2) for 14 days. VIP-LI was significantly increased in carotid bodies of hypoxic animals (204% vs. normoxic animals). On the other hand, VIP-LI was decreased in the anterior pituitary (-68%), suprachiasmatic nuclei (-29%) and periventricular nuclei (-26%). No significant variation in VIP-LI was observed in other peripheral structures and discrete brain area studied. These results suggest that long-term hypoxia induces alterations in VIP systems implicated in chemoreception, biological rhythms and neuroendocrine functions.

Animals↗

Immunocytochemical study of the CLIP/ACTH-immunoreactive nerve fibres in the dorsal raphe nucleus of the rat.

The injection of corticotrophin-like intermediate lobe peptide (CLIP) in the lateral ventricle or the dorsal raphe nucleus (DRN) of the rat is followed by a significant increase in the amount of paradoxical sleep. In the DRN, CLIP would act through a somatic and/or dendritic release of serotonin. To establish the anatomical basis of these effects, the nerve fibres immunoreactive for CLIP/ACTH were labelled and their fine anatomical relationships with the neuronal elements of the DRN were studied at the ultrastructural level. Half of the profiles of labelled varicosities were 'free' in the neuropile, the other half was in close contact with dendrites, either shafts or spines. It was interesting to note that few contacts with dendritic shafts were under the form of a synapse, whereas a large number of the contacts with spines were synaptic. The chemical nature of these dendritic targets remains to be determined but preliminary results indicate that they are partly serotoninergic.

Adrenocorticotropic Hormone↗

Afferents to the nucleus reticularis parvicellularis of the cat medulla oblongata: a tract-tracing study with cholera toxin B subunit.

The aim of this study was to examine anatomical evidence in cats of whether the nucleus reticularis parvicellularis (Pc) is part of the circuit responsible for the inhibition of brainstem motoneurons during paradoxical sleep. For this purpose, we made iontophoretic injections of the retrograde and anterograde tracer cholera toxin B subunit (CTb) in the Pc. After CTb injections in the Pc, a large number of retrogradely labeled neurons were seen in the central nucleus of the amygdala, the lateral part of the bed nucleus of the stria terminalis, the posterior hypothalamic areas, the mesencephalic reticular formation, the nucleus locus subcoeruleus, the nucleus pontis caudalis, other portions of the Pc, the nucleus reticularis dorsalis, the trigeminal sensory complex, and the nucleus of the solitary tract. We further found that the Pc receives 1) serotoninergic afferents from the raphe dorsalis, magnus, and obscurus nuclei; 2) noradrenergic inputs from the dorsolateral pontine tegmentum; 3) cholinergic afferents from the lateral medullary reticular formation; 4) substance P-like afferents from the central nucleus of the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, and nucleus of the solitary tract; and 5) methionine-enkephalin-like projections from the periaqueductal gray, the nucleus of the solitary tract, the lateral pontine and medullary reticular formation, and the spinal trigeminal nucleus. We further found that the Pc do not receive afferents from brainstem structures responsible for muscle atonia, such as the ventromedial medulla and the dorsomedial pontine tegmentum, and therefore may not be part of the circuit inhibiting the brainstem motoneurons during paradoxical sleep.

Animals↗

Hypothalamo-preoptic histaminergic projections in sleep-wake control in the cat.

Cats were chronically implanted with electrodes for polygraphic recordings and cannulae for intracerebral microinjections in order to study the functional role of histaminergic innervation of the preoptic-anterior hypothalamus in sleep-wake control. alpha-Fluoromethylhistidine (alpha FMH, 50 micrograms in 1 microliter), a specific inhibitor of the histamine-synthesizing enzyme, when injected bilaterally into the preoptic area, where numerous histaminergic fibres and terminal-like structures are present, caused a significant increase in deep slow wave sleep (S2) and paradoxical sleep (PS) and a decrease in wakefulness. In contrast, microinjections of histamine (5 or 30 micrograms in 1 microliter) in the same area dose-relatedly increased wakefulness and decreased both slow wave sleep and paradoxical sleep. The effects of histamine were reduced by pretreatment with mepyramine (1 mg/kg i.p.), a well known histamine H1 receptor antagonist, and were mimicked by a local injection of impromidine (1 microgram in 1 microliter), a potent histamine H2 receptor agonist. Microinjections of mepyramine alone (120 micrograms in 1 microliter) caused an increase in slow wave sleep. These results suggest that preoptic histaminergic innervation is involved in sleep-wake control and that the action might be mediated via both H1 and H2 receptors.

Animals↗

Is the nucleus raphe dorsalis a target for the peptides possessing hypnogenic properties?

Several peptides exhibiting hypnogenic properties when administered i.p., i.v. or i.c.v. are now known. No data, however, are available concerning their targets in the brain. In the present work we hypothesize that the nucleus raphe dorsalis (nRD) may be one such target since it contains 2 sleep permissive components that must be influenced for sleep to occur. One of these components is serotoninergic in nature and gates the occurrence of ponto-geniculo-occipital (PGO) waves. The other, of unknown nature, influences tonic sleep phenomena. For hypnogenic peptides, a putative mechanism permitting the triggering and maintenance of sleep might consist of influencing both the above components. In the present work, 3 hypnogenic substances, CLIP (corticotropin-Like intermediate lobe peptide), VIP (vasoactive intestinal polypeptide) and DSIP (delta sleep inducing peptide), were injected into the nRD in order to determine whether these compounds still induce sleep by local administration. To verify that such local injections do not spread outside the nRD, radiolabelled CLIP and VIP were also injected. Autoradiograms obtained with either labeled CLIP or VIP indicate that these compounds, injected in a 0.2 microliter volume, do not spread outside the nRD. The sleep data obtained confirm that CLIP, at a dose of 10 ng, induces an increase in duration of paradoxical sleep (PS); this effect is observed only for injection sites located in the dorsolateral part of the nRD, an area where CLIP immunoreactive (IR) fibers are present. VIP, at a dose of 100 ng, also increases PS duration, whereas at 10 ng, only slow wave sleep duration is increased. In this case, the positive injection sites are scattered throughout the entire nRD as are the VIP-IR fibers. With DSIP, no sleep effect was found whatever the dose used or the site injected; in the same manner, no DSIP-IR fibers have been located in this structure. These data suggest that the nRD is a target for the expression of the hypnogenic properties of CLIP and VIP, but not for DSIP. The nature of the possible mechanisms permitting such expression are discussed.

Adrenocorticotropic Hormone↗

Experimental evidence of penile erections during paradoxical sleep in the rat.

We have developed a new technique to chronically monitor penile erections in the rat across behavioural states. This technique, involving chronic erectile tissue pressure monitoring and simultaneous ischiocavernosus and bulbospongiosus (IC-BS) muscle electromyography, demonstrates for the first time that rats exhibit penile erections during paradoxical sleep (PS). No erectile events were observed during slow wave sleep. These PS-related erectile events were similar to visually confirmed, waking state, erections in that they were associated with an increase in baseline erectile tissue pressure and, with IC-BS muscle bursts, dramatic suprasystolic penile pressure peaks often greater than 1000 mmHg. PS-related erections were 11 +/- 7 s in duration and were observed in 28.5% of all PS episodes. This method of chronic penile erection monitoring in the rat provides a new animal model for investigating neural mechanisms of sleep-related erections.

Animals↗

Long-term variations of arterial blood pressure during sleep in freely moving cats.

Using a new telemetric system for arterial blood pressure recordings, we have investigated long-term postoperative changes in blood pressure during sleep in freely moving cats. Particular attention was paid to the transitional periods at the beginning and end of paradoxical sleep (PS), as well as to the relationship between the blood pressure and ponto-geniculo-occipital (PGO) waves. In the initial postoperative stage lasting 2 to 5 days, the blood pressure decreased during the transition from slow wave sleep (SWS) to PS and maintained its lower level until the end of PS. In contrast, in the later chronic stage, the blood pressure increased tonically during the transition from SWS to PS and maintained its higher level throughout PS on which several phasic rises in blood pressure were superimposed. A significant increase in arterial pressure during the transitional period began shortly after the first appearance of PGO waves. On the other hand, significant phasic rises in arterial pressure during PS shortly preceded the onset of PGO wave bursts.

Animals↗