Papers by Pierre-hervé Luppi
The Journal of Comparative Neurology, 1994
The aim of this study was to examine anatomical evidence in cats of whether the nucleus reticular... more 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.
Current Opinion in Neurobiology, 2013
The authorshave no conflicts of interest to declare.
Sleep Medicine
This article focuses on the contributions made by Michel Jouvet concerning the systems responsibl... more This article focuses on the contributions made by Michel Jouvet concerning the systems responsible for the muscle atonia of paradoxical sleep (REM sleep). He was the first to describe the brainstem system mechanisms responsible for muscle atonia during paradoxical sleep using pontine cats and localized pontine lesions. Also discussed is the research going on in the eighties, when Michel Jouvet was hunting for the hypnogenetic factor. At that time, he thought that it was secreted by the hypophysis; but it finally turned out to be controlled by the hypocretin/orexin and melanin concentrating hormone neurones located in the lateral hypothalamus. Several unforgetable moments with Michel Jouvet are described which occurred between 1983 and his last moments with us.
Posterior hypothalamus and regulation of vigilance states
Archives italiennes de biologie, 2004
International audienc
Efficient paradoxical (REM) sleep homeostatic regulation in mice: reports on sleep architecture and neuronal activation
International audienc
Sleep, Jan 7, 2018
Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepines... more Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. The three latter symptoms together with a short REM sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates. We first performed 48hrs of REM sleep deprivation using the classic small-platforms-over-water method. We found that narcoleptic mice are similarly REM sleep deprived to WT mice. Although they had shorter sleep latency, Orex-KO mice recovered similarly to WT during the following 10hrs of recovery. Interestingly, Orex-KO mice also had cataplexy episodes immediately after REM sleep deprivation, anticipating REM sleep rebound, at a time of day when cataplexy ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 8, 2017
Almost all areas of the neocortex are connected with the claustrum, a nucleus located between the... more Almost all areas of the neocortex are connected with the claustrum, a nucleus located between the neocortex and the striatum, yet the functions of corticoclaustral and claustrocortical connections remain largely obscure. As major efforts to model the neocortex are currently underway, it has become increasingly important to incorporate the corticoclaustral system into theories of cortical function. This Mini-Symposium was motivated by a series of recent studies which have sparked new hypotheses regarding the function of claustral circuits. Anatomical, ultrastructural, and functional studies indicate that the claustrum is most highly interconnected with prefrontal cortex, suggesting important roles in higher cognitive processing, and that the organization of the corticoclaustral system is distinct from the driver/modulator framework often used to describe the corticothalamic system. Recent findings supporting roles in detecting novel sensory stimuli, directing attention and setting be...
Sleep, 2016
Study Objectives: It is commonly accepted that sleep is beneficial to memory processes, but it is... more Study Objectives: It is commonly accepted that sleep is beneficial to memory processes, but it is still unclear if this benefit originates from improved memory consolidation or enhanced information processing. It has thus been proposed that sleep may also promote forgetting of undesirable and non-essential memories, a process required for optimization of cognitive resources. We tested the hypothesis that non-rapid eye movement sleep (NREMS) promotes forgetting of irrelevant information, more specifically when processing information in working memory (WM), while REM sleep (REMS) facilitates the consolidation of important information. Methods: We recorded sleep patterns of rats trained in a radial maze in three different tasks engaging either the long-term or short-term storage of information, as well as a gradual level of interference. Results: We observed a transient increase in REMS amount on the day the animal learned the rule of a long-term/reference memory task (RM), and, in contrast, a positive correlation between the performance of rats trained in a WM task involving an important processing of interference and the amount of NREMS or slow wave activity. Various oscillatory events were also differentially modulated by the type of training involved. Notably, NREMS spindles and REMS rapid theta increase with RM training, while sharp-wave ripples increase with all types of training. Conclusions: These results suggest that REMS, but also rapid oscillations occurring during NREMS would be specifically implicated in the long-term memory in RM, whereas NREMS and slow oscillations could be involved in the forgetting of irrelevant information required for WM.
Altérations du sommeil en réponse à la modulation par pharmacogénétique de l’activité des neurones exprimant l’hormone de mélano-concentration
Médecine du Sommeil, 2016
Objectif De nombreux rapports suggerent que les neurones hypothalamiques exprimant l’hormone de m... more Objectif De nombreux rapports suggerent que les neurones hypothalamiques exprimant l’hormone de melano-concentration (MCH) pourraient jouer un role dans le cycle veille-sommeil. Neanmoins leur contribution exacte a la regulation du sommeil lent (SL) et/ou du sommeil paradoxal (SP) reste largement debattue. Methodes Des souris transgeniques MCH-cre ont recu des injections bilaterales d’un vecteur viral permettant l’expression specifiquement dans les neurones MCH d’un recepteur muscarinique mute excitateur ou inhibiteur, rendu insensible a l’acetylcholine et seulement activable par un ligand exogene (CNO) administre par voie intraperitoneale. Ces souris ont ensuite ete appareillees pour realiser des enregistrements polysomnographiques chroniques. Apres 4 semaines de recuperation, les effets sur le sommeil de l’excitation ou de l’inhibition des neurones MCH ont ete evalues en reponse a l’administration de CNO. Resultats L’inhibition des neurones MCH au debut de la phase diurne conduit a une augmentation des quantites de SL due a une augmentation importante de la duree des episodes. A l’inverse, l’excitation des neurones MCH conduit a une diminution de la duree des episodes de SL. Concernant le SP, l’inhibition des neurones MCH ne produit pas d’effet majeur alors que leur excitation facilite son declenchement et sa consolidation. Conclusion Ces resultats suggerent que les neurones MCH jouent un role important dans la regulation fine du cycle veille-sommeil en modulant le SL et le SP. En particulier, ils faciliteraient la consolidation du SL ainsi que la promotion et le maintien du SP.
The Network Responsible for Paradoxical Sleep Onset and Maintenance
Circuits and Functions, 2004
International audienc
Régulation homéostasique du sommeil paradoxal chez la souris narcoleptique
Médecine du Sommeil, 2015
Objectif Certains symptomes de la narcolepsie comme la cataplexie ou la paralysie du sommeil sont... more Objectif Certains symptomes de la narcolepsie comme la cataplexie ou la paralysie du sommeil sont consideres comme des etats dissocies du SP, suggerant une deregulation du SP. Vu et al. (2009) ont montre, chez 6 patients narcoleptiques, qu’il est plus difficile de priver de SP les patients que les temoins. Aucune etude de ce type n’a ete realisee chez la souris narcoleptique. L’objectif de notre etude est donc d’etudier la regulation homeostasique du SP chez la souris narcoleptique hypocretine KO. Methodes Des souris sauvages (WT) et KO ont ete privees specifiquement de SP par la methode « piscine » durant 48 h. Apres privation, les souris sont replacees dans leur baril d’enregistrement pendant 24 h. Nous etudions ainsi leur capacite a recuperer leur dette de SP. Dans une deuxieme experience, des souris WT et KO ont ete privees de SP durant 48 h a l’aide de notre nouvelle methode de privation automatique. Lorsqu’un episode de SP est detecte, un signal TTL envoye par l’ordinateur secoue le fond de la cage et ainsi reveille la souris. Le nombre de stimulation correspond au nombre de tentatives d’entree en SP. C’est un bon marqueur de la pression de SP. Resultats Apres privation piscine, les souris KO font un rebond de SP similaire a celui des souris WT suggerant une regulation homeostasique du SP intacte. Cependant, ce rebond est plus precoce chez les KO (20 ± 4,2 min) que chez les WT (113 ± 5,6 min). En utilisant la methode de privation de SP automatique, nous avons pu observe que le nombre de stimulation est plus important chez les souris KO (782,3 ± 60,7) que chez les WT (367,6 ± 42,0), revelant une pression de SP accrue chez les souris KO. De plus, les souris WT ont une pression de SP plus elevee durant la phase eclairee que pendant la phase obscure conformement a la distribution circadienne du SP. En revanche, les souris KO ont une pression de SP s’accumulant de facon similaire dans les deux phases. Conclusion Nos donnees suggerent qu’une pression de SP accrue chez les souris KO serait a l’origine de du rebond precoce de SP et qu’il y aurait un defaut d’inhibition du SP chez les souris narcoleptiques.
Functional Neuroanatomical Considerations on Afferent and Efferent Projections of the Nucleus Raphe Magnus
Thermal Balance in Health and Disease, 1994
The nucleus raphe magnus (NRM) is part of the thermoafferent system of the brainstem (1, 2). Ther... more The nucleus raphe magnus (NRM) is part of the thermoafferent system of the brainstem (1, 2). Thermoregulatory effects have been shown medially inside the NRM, not at all however in lateral parts of the NRM and in the gigantocellular medullary reticular formation (2). Adaptive effects to cold temperatures have been demonstrated in the NRM (3, 4). These effects are still partly maintained after complete microtranssection of the descending afferents to the NRM, suggesting that they are partly generated by descending influences from upper structures inside the brain, partly by structures of the lower brainstem. An aim of this study has been to find the structures involved in thermoadaptive effects inside the NRM.
Médecine du Sommeil, 2013
sleep. This inhibition allows the glutamatergic neurons of the sublaterodorsal tegmental nucleus ... more sleep. This inhibition allows the glutamatergic neurons of the sublaterodorsal tegmental nucleus to be activated. These neurons are responsible for cortical activation, via thalamic projections, and for muscle atonia, via glycinergic neurons of the medullary reticular formation.
The lateral paragigantocellular nucleus (LPGi) is located in the ventrolateral medulla and is kno... more The lateral paragigantocellular nucleus (LPGi) is located in the ventrolateral medulla and is known as a sympathoexcitatory area involved in the control of blood pressure. In recent experiments, we showed that the LPGi contains a large number of neurons activated during PS hypersomnia following a selective deprivation. Among these neurons, more than two-thirds are GABAergic and more than one fourth send efferent fibers to the wake-active locus coeruleus nucleus. To get more insight into the role of the LPGi in PS regulation, we combined an electrophysiological and anatomical approach in the rat, using extracellular recordings in the head-restrained model and injections of tracers followed by the immunohistochemical detection of Fos in control, PS-deprived and PS-recovery animals. With the head-restrained preparation, we showed that the LPGi contains neurons specifically active during PS (PS-On neurons), neurons inactive during PS (PS-Off neurons) and neurons indifferent to the sleep-waking cycle. After injection of CTb in the facial nucleus, the neurons of which are hyperpolarized during PS, the largest population of Fos/CTb neurons visualized in the medulla in the PS-recovery condition was observed in the LPGi. After injection of CTb in the LPGi itself and PS-recovery, the nucleus containing the highest number of Fos/CTb neurons, moreover bilaterally, was the sublaterodorsal nucleus (SLD). The SLD is known as the pontine executive PS area and triggers PS through glutamatergic neurons. We propose that, during PS, the LPGi is strongly excited by the SLD and hyperpolarizes the motoneurons of the facial nucleus in addition to local and locus coeruleus PS-Off neurons, and by this means contributes to PS genesis.
[Histamine-immunoreactive neurons in the hypothalamus of cats]
Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie, 1986
The localization of histaminergic neurons in the cat brain was determined immunohistochemically w... more The localization of histaminergic neurons in the cat brain was determined immunohistochemically with an antibody against histamine. We found that histamine-immunoreactive neurons are observed exclusively in the posterior hypothalamus of colchicine treated cats. The larger group of neurons was found in the ventrolateral part of the posterior hypothalamus, including the tuberomammillary nucleus. Histamine-positive neurons were also observed in the supramammillary area and adjacent posterior hypothalamic area, as well as in the peri- and premammillary regions. In addition, numerous histamine immunoreactive fibers were detected, not only in the posterior hypothalamus, but also in other brain areas, such as the preoptic area of the anterior hypothalamus.
Sleep Medicine, 2014
When this paper was originally published the affiliation for Giuseppe Plazzi was incorrect. The c... more When this paper was originally published the affiliation for Giuseppe Plazzi was incorrect. The correct affiliations are listed above.
Neuroscience, 2005
Recent research has shown that neurons in the ventrolateral preoptic nucleus are crucial for slee... more Recent research has shown that neurons in the ventrolateral preoptic nucleus are crucial for sleep by inhibiting wake-promoting systems, but the process that triggers their activation at sleep onset remains to be established. Since evidence indicates that sleep induced by adenosine, an endogenous sleep-promoting substance, requires activation of brain A 2A receptors, we examined the hypothesis that adenosine could activate ventrolateral preoptic nucleus sleep neurons via A 2A adenosine receptors in rat brain slices. Following on from our initial in vitro identification of these neurons as uniformly inhibited by noradrenaline and acetylcholine arousal transmitters, we established that the ventrolateral preoptic nucleus comprises two intermingled subtypes of sleep neurons, differing in their firing responses to serotonin, inducing either an inhibition (Type-1 cells) or an excitation (Type-2 cells). Since both cell types contained galanin and expressed glutamic acid decarboxylase-65/67 mRNAs, they potentially correspond to the sleep promoting neurons inhibiting arousal systems. Our pharmacological investigations using A 1 and A 2A adenosine receptors agonists and antagonists further revealed that only Type-2 neurons were excited by adenosine via a postsynaptic activation of A 2A adenosine receptors. Hence, the present study is the first demonstration of a direct activation of the sleep neurons by adenosine. Our results further support the cellular and functional heterogeneity of the sleep neurons, which could enable their differential contribution to the regulation of sleep. Adenosine and serotonin progressively accumulate during arousal. We propose that Type-2 neurons, which respond to these homeostatic signals by increasing their firing are involved in sleep induction. In contrast, Type-1 neurons would likely play a role in the consolidation of sleep.
Neuroscience, 1994
Supraspinal a&rents to the pentine micturition center, Barrington's nucleus, were investigated in... more Supraspinal a&rents to the pentine micturition center, Barrington's nucleus, were investigated in the rat by visualization of the retrograde tracer, cholera-toxin subunit B, in neurons following iontophoretic injection into Barrington's nucleus. Tissue sections from five rats with injections primarily localized in Barrington's nucleus revealed numerous retrogradely labeled neurons throughout all rostrocaudal levels of the ~~aqu~uctal gray (particularly its ventrolatemi division), in the lateral hypothalamic area (particularly medial to the fornix), and in the medial preoptic nucleus. Retrogfadely labeled neurons were also consistently found in the nucleus of the solitary tract, in the vicinity of the lateral reticular nucleus, nucleus paragigantocellularis, parabrachial nucleus, KSlliker-Fuse nucleus, cuneiform nucleus, raphe nucleus and zona incerta. In the hypothalamus, in addition to the perifornical region, retrogradely labeled neurons were found in all cases in the tuberomammill~ nucleus, premammilla~ nucleus, dorsal hy~thalamic area, ventrom~ial h~othalamic nucleus, and the paravent~c~ar nucleus. At more rostra1 levels, in addition to the medial preoplic area, retrogradely labeled neurons were seen in the bed nucleus of the stria terminalis and in a region just lateral to the supraoptic nucleus near the medial amygdaloid nucleus. Retrogradely labeled neurons were also observed in the motor, insular, and infralimbic cortices. Injections of anterograde tracers (cholera-toxin subunit B or Phuseolus vulgaris leucoagglutinin) into the K~iliker-Fur nucleus, the ventrola~ral ~~aqu~u~tal gray, lateral hypothalamic area, or medial preoptic area, resulted in fiber labeling within Barrington's nucleus, confirming the retrograde tracing studies. As previously reported, numerous neurons in Barrington's nucleus were immunoreactive for corticotropin-releasing hormone. Double-labeling studies revealed afferent fibers from the periaqueductal gray and lateral hypothalamic area overlapping the corticotropin-releasing hormone-immunorea~ive neurons of Bar~n~on's nucleus, and in some cases anterogmdely labeled fibers with varcosities appeared to target these neurons. The present results suggest that Barrington's nucleus in the rat receives neuronal inputs from brainstem nuclei as well as from forebrain limbic structures including hypothalamic nuclei, the medial preoptic nucleus, and cortical areas involved in fluid balance or blood pressure regulation. In light of the role of Barrington's nucleus in mi~urition, the integration of these various inputs may be important for coordinating urinary fun&on with fluid and cardiovascular homeostasis. Additionally, as neurons in Barrington's nucleus are immunoreactive for the stress-related neurohormone, corticotropin-releasing hormone, these diverse inputs may regulate stress-related functions of this nucleus.
Neurophysiologie Clinique/Clinical Neurophysiology, 2013
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Papers by Pierre-hervé Luppi