A Anatomia comparativa de mamíferos vem sendo tema de pesquisas, nas áreas biomédica e biológica com o objetivo de se buscar conhecimentos que possam auxiliar na busca sobre o entendimento do binômio unidade-variedade, dentre os símios tem sido particularmente enfocados o Babuíno e o Rhesus que, entretanto, não são próprios do Novo Mundo. O Cebus apella, animal das matas do continente Sul-americano, distribuindo-se geograficamente por quase todo o Brasil, apresenta satisfatória adaptação à vida em cativeiro condição em que, inclusive, se reproduz com facilidade. Assim, é de nosso interesse focalizar, o Cebus apella, analisando a origem, a composição e os nervos resultantes de seu plexo braquial. O objetivo imediato deste trabalho é, dar seqüência ao conhecimento de sua Anatomia, visando também o fornecimento de subsídios para interpretações anatómo-funcionais do Cebus apella, comparativamente a outros animais. O objetivo a médio e a longo prazos é o estabelecimento do padrão anatômico deste animal, culminando com a elaboração de um Atlas - texto sobre a Anatomia do macaco Cebus apella. Utilizamos 20 animais, sendo 10 machos e 10 fêmeas, adultos, pertencentes ao acervo de pesquisas da Universidade Federal de Uberlândia. A preparação das peças anatômicas foi feita segundo a metodologia usual em estudos anatômicos. Os principais nervos oriundos do plexo braquial são: supraescapular, subescapular, musculocutâneo, radial, mediano, ulnar, axilar, toracodorsal, peitoral maior e peitoral menor. Em 57% dos espécimes dissecados o plexo braquial do Cebus está constituído por raízes de C5 a T1, em 21,4% de C5 a T2, em 14,3% de C4 a T1 e em 7,3% de C4 a T2. O plano dorsal do plexo braquial contribui para a formação dos nervos: frênico, peitoral maior e peitoral menor. O plano médio origina os nervos musculocutâneo, mediano, ulnar e cutâneo medial do antebraço, enquanto o plano ventral dá origem aos nervos supraescapular, subescapular, axilar, radial e torácico longo. Discute-se a ocorrência de pré e de pós-fixação do plexo, bem como a de seu deslocamento cranial e caudal. Em conclusão o plexo braquial do Cebus apella está constituído por raízes de C5 a T1 e é organizado em um plano ventral mais simples, um médio de complexidade intermediária e um dorsal mais complexo. / Comparative Anatomy of mammals has been a relevant theme of researches in the biomedical and biological areas with the objective of looking for more information that can aid for searching on the understanding of the unit-variety complex. Among the simians, Baboon and Rhesus have been particularly focused, although they are not from the New World. The monkey Cebus apella, animal of the forests of the South American continent, being geographically distributed for almost the whole Brazil, presents satisfactory adaptation to the captive life showing a great easiness of reproduction. Thus, we intended to study the monkey Cebus apella, analyzing the origin, the composition and the resulting nerves of its brachial plexus. The immediate objective of this study was to add information to the knowledge of its Anatomy, seeking the supply of subsidies for anatomo-functional interpretations of Cebus apella comparatively to humans and domestic animals. Further, we propose to establish the anatomical pattern of this animal, culminating with the elaboration of an Atlas - text on the Anatomy of the monkey Cebus apella. Twenty adult animals, 10 male and 10 female, belonging to the collection of anatomical pieces of the Anatomy Laboratory of the Federal University of Uberlândia were obtained and prepared through fixation and dissection. The major nerves originating from the brachial plexus were: the suprascapular, the subscapular, the musculo-cutaneous, the radial, the median, the ulnar, the axillary, the thoraco-dorsal, the pectoralis major and the pectoralis minor. In the dissected specimens, the brachial plexus of Cebus apella was constituted by the roots from C5 to T1 (55,00 ± 11,12%), from C5 to T2 (25,00 ± 9,68%), from C4 to T1 (15,00 ± 7,98%) and from C4 to T2 (5,00 ± 4,87%). The ventral plan of the brachial plexus contributed for the formation of the following nerves: the phrenic, the subclavius, the pectoralis major, and the pectoralis minor. The medium plan originated the musculo-cutaneous, the median, the ulnar, and the forearm medial cutaneous nerves, while the dorsal plan originated the suprascapular, the subscapular, the axillary, the radial, thoraco-dorsal and the long thoracic nerves. In addition, the occurrence of pre- and post- fixation of the plexus as well as its cranial and caudal displacement have been discussed. In conclusion, the brachial plexus of Cebus apella constituted by the roots from C5 to T1 is organized in a simpler ventral plan, a medium plan of intermediate complexity and a more complex dorsal plan.

La grande variété de morphologie de l’appareil visuel chez les arthropodes en fait un groupe unique pour l’étude de la diversité et l'évolution du système visuel. Cependant, la plupart de nos connaissances sur le développement et l'architecture neurale du système visuel provient de quelques organismes modèles. Mon projet vise à contribuer à l'étude de la diversité et de l'évolution du système visuel des arthropodes en étudiant l'œil du crustacé Parhyale hawaiensis; axé sur son développement, sa neuro-architecture et sa fonction. En particulier, mon travail vise à caractériser la structure du système visuel, à cartographier les connexions entre les photorécepteurs (PR) et le lobe optique (LO) et à comprendre les adaptations fonctionnelles de l'œil, par rapport aux yeux des autres arthropodes.Une description de l'anatomie de base du système visuel a été réalisée au moyen de la microscopie électronique, par immunomarquage et par la production de lignées de transgénique. J'ai trouvé que Parhyale possède un œil composé de type apposition avec 8 (chez les nouveau-nés) à 50 (chez les adultes) ommatidies, chacun formée par 5 PR (R1-R5). Nous avons trouvé deux opsines, nommés Ph-Opsin1 et Ph-Opsin2, exclusivement exprimés dans la rétine. En utilisant la séquence génomique comme guide, j'ai cloné des séquences régulatrices en amont de chaque gène d’opsine et généré des rapporteurs transgéniques qui récapitulent les patterns d'expression de Ph-Opsin1 et de Ph-Opsin2. Ces rapporteurs ont révélé que R1-R4 exprime Ph-Opsin1 tandis que R5 exprime le Ph-Opsin2.Immunomarquage ainsi que l'imagerie des deux lignées transgéniques, ont montré que les PR envoient de longues projections depuis la rétine au LO. Trois neuropiles optiques ont été identifiés: la lamina, la medulla et un neuropile plus profond qui est probablement la lobula plate ou la lobula. En suivant les projections axonales des PR dans le cerveau, révélant que tous les PR se projettent dans la lamina. Ceci diffère de ce qui a été montré chez les diptères et les crustacés, où au moins un PR par ommatidie projette ses axones dans la medulla.La microscopie électronique a montré que les rhabdomères des deux paires de PR, R1 + R3 et R2 + R4, sont orthogonalement alignés les uns aux autres dans chaque ommatidie, et que le rhabdome ne tourne pas. Ces caractéristiques rendent les PR intrinsèquement sensibles aux directions spécifiques de la lumière polarisée. Par conséquent, j'ai essayé de comprendre si Parhyale réagît à la lumière polarisée, au moyen d'expériences comportementales. Les données que j'ai recueillies suggèrent que Parhyale sont phototactiques pour la lumière blanche mais ne montrent aucune réponse à la lumière polarisée dans ces essais expérimentaux. Les problèmes potentiels liés à ces tests de comportement sont discutés.Enfin, je montre que l'œil de Parhyale s'adapte rapidement à différentes conditions d'intensité lumineuse. Ceci est obtenu par le mouvement des granules de pigments, situés à l'intérieur des PR, et par des changements morphologiques de la membrane basale du PR.Ce projet est pionnier dans l'étude du système visuel chez Parhyale. C'est la première fois que des outils génétiques ont été introduits pour étudier le système visuel de crustacés. Il établit Parhyale comme un puissant système expérimental pour des études in vivo de développement des yeux composé et de ciblage axonal du système visuel, un champ actuellement dominé par des études sur une seule espèce de mouche. / The wide diversity of eye designs present in arthropods makes them a unique group for studying the diversity and evolution of the visual system. However, most of our knowledge on the development and the neural architecture of the visual system comes from few model organisms. My project aims to contribute to the study of the diversity and evolution of the arthropod visual system by studying the eye of the crustacean Parhyale hawaiensis; focusing on its development, neuroarchitecture and function. In particular, my work aims to characterize the structure of the visual system, to map the connections between photoreceptors (PR) and optic lobe (OL) and to understand the functional adaptations of the eye, in relation to the eyes of other arthropods.A description of the basic anatomy of the visual system was performed by means of electron microscopy, immunostainings and by generating transgenic reporter lines. I found that Parhyale has an apposition-type compound eye with 8 (in hatchlings) to 50 (in adults) ommatidia, each one formed by 5 PR cells (R1-R5).Two opsins were found in Parhyale, named Ph-Opsin1 and Ph-Opsin2, which are exclusively expressed in the retina. Using the genome sequence as a guide, I cloned upstream regulatory sequences from each opsin genes and generated transgenic reporters that recapitulate the expression patterns of Ph-Opsin1 and Ph-Opsin2. These reporters revealed that R1-R4 express Ph-Opsin1 while R5 expresses Ph-Opsin2.Immunostainings and live imaging of the two transgenic lines showed that PR cells send long projections from the retina to the OL, via an optic nerve. Three optic neuropils were identified: lamina, medulla and a deeper neuropil, possibly the lobula or lobula plate. Following the axonal projections of the PR into the brain, revealed that all PR project to the lamina. This differs from what has been shown in dipterans and crustaceans, where at least one PR per ommatidium projects to the medulla. Electron microscopy showed that the rhabdomeres of two pairs of PR, R1+R3 and R2+R4, are orthogonally aligned to each other in each ommatidium, and that the rhabdom does not rotate. These features render the PR intrinsically sensitive to specific directions of light polarisation. Therefore, I tried to understand whether and how Parhyale respond to polarised light. I developed two experimental setups to address whether Parhyale shows behavioural responses triggered by light polarisation. The data I have collected suggest that Parhyale are phototactic to dim white light but show no response to polarised light in these specific experimental assays. Potential problems with these behavioural assays are discussed.Finally I show that the eye of Parhyale quickly adapts to different conditions of light intensity. This is achieved by movement of the shielding pigment granules, located inside the PR cells and by morphological changes of the PR basal membrane.This project is pioneering the study of the visual system in Parhyale. It is the first time that genetic tools have been introduced to study the crustacean visual system. It establishes Parhyale as a powerful experimental system for in vivo studies of compound eye development and axonal targeting, a field currently dominated by studies in a single species of fruitfly.

La dyslexie développementale est un trouble spécifique de l'apprentissage de la lecture qui affecte 3 à 7% des enfants d'âge scolaire. Il est bien établi aujourd'hui que la dyslexie découle en partie de variations génétiques qui causent des changements lors du développement cérébral, qui, à leur tour, ont des conséquences au niveau cognitif. Cette thèse s'appuie sur les analyses morphométriques de trois des sillons principaux du cerveau dans trois grands ensembles de données d'imagerie par résonance magnétique : 102 participants français, 80 participants polonais et 70 participants allemands, avec, dans chaque jeu de données, environ la moitié de participants ayant été diagnostiqués dyslexiques et la moitié de lecteurs normaux. J'ai étudié le sillon central, la scissure Sylvienne et le sillon temporal supérieur grâce aux outils de labellisation automatique et de mesures du logiciel BrainVISA. J'ai mesuré des propriétés quantitatives (surface et profondeur) ainsi que des propriétés qualitatives (configuration) de chaque sillon. J'ai montré une triple interaction entre groupe, sexe et hémisphère dans la profondeur moyenne du sillon central, laissant penser que les participants contrôles et dyslexiques diffèrent en terme d'asymétrie de profondeur de ce sillon. Comme la sulcation est un processus se déroulant de façon précoce lors du développement du cerveau et qui semble moins plastique que d'autres mesures cérébrales (comme, par exemple, les volumes de matière grise), ce résultat pourrait s'avérer être un marqueur précoce du risque de dyslexie plutôt que la conséquence de mauvaises capacités de lecture. / Developmental dyslexia is a specific disorder of reading acquisition that affects 3 to 7% of school-aged children. It is well established that dyslexia is partly caused by genetic variations whitch cause changes in brain development, whitch then have consequences at the cognitive level. This Ph.D thesis is based on morphometry analysis of three main sulci of the brain in three large databases of brain magnetic resonance images: 102 participants from France, 80 particpants from Poland and 70 participants from Germany, with, in each database, about half of participants were diagnosed with dyslexia and half of normal readers. I have studied the central sulcus, the Sylvian fissure and the superior temporal sulcus thanks to the automatic labelisation and measures tools in the BrainVISA software. I have measured some quantitative properties (surface and depth) as well as some qualitative ones (configuration) of each sulcus. I have shown a triple interaction between group, sex and hemisphere in the mean depth of the central sulcus. This result allows us to think that control and dyslexic participants may be different in terms of depth asymetry in this particular sulcus. Given that sulcation is an early process during brain development et that it seems to be less plastic than other brain measures (like, for example, grey matter volumes), this result may be an early marker of risk factors for dyslexia rather than a consequence of poor reading.

The circadian timing system establishes daily rhythms in behavior and physiology throughout the body, ensuring that functions like activity, sleep and hormone release are appropriately timed. Research suggests that his temporal synchrony within the body is quite important for health and survival. In mammals, the central circadian pacemaker in the suprachiasmatic nucleus (SCN) drives rhythms in behavior and physiology in large part by stimulating or inhibiting other brain regions responsible for these functions at the appropriate times of day. This timed signal is often indirect, i.e. relayed or possibly processed through a series of neurons in different brain regions before reaching the effector site. The subparaventricular zone (SPZ), a region adjacent to the SCN which is the main recipient of direct neuronal inputs from the SCN, is thought to be a critical relay for SCN signals, since loss of the SPZ results in loss of circadian rhythms in body temperature, activity and sleep/wakefulness. Another important relay site, the dorsomedial hypothalamic nucleus (DMH) gets direct input from both the SCN and SPZ and is critical for normal expression of various circadian rhythms.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a profound loss of dopaminergic neurons from the substantia nigra (SN). Among the many pathogenic mechanisms thought to be responsible for the demise of these cells, dopamine (DA)-dependent oxidative stress and oxidative damage has taken center stage due to extensive experimental evidence showing that DA-derived reactive oxygen species (ROS) and oxidized DA metabolites are toxic to SN neurons. Despite its being the most efficacious drug for symptom reversal in PD, there is concern that levodopa (LD) may contribute to the neuronal degeneration and progression of PD by enhancing DA concentrations and turnover in surviving dopaminergic neurons. The present study investigates the potential neurotoxic and neuroprotective effects of DA in vitro. These effects are compared to the toxicity and neuroprotective effects observed in the rat striatum after the administration of LD and selegiline (SEL), both of which increase striatal DA levels. The effects of exogenous LD and/or SEL administration on both the oxidative stress caused by increased striatal iron (II) levels and its consequences have also been investigated. 6-Hydroxydopamine (6-OHDA) is a potent neurotoxin used to mimic dopaminergic degeneration in animal models of PD. The formation of 6-OHDA in vivo could destroy central dopaminergic nerve terminals and enhance the progression of PD. Inorganic studies using high performance liquid chromatography with electrochemical detection (HPLC-ECD) show that hydroxyl radicals can react with DA to form 6-OHDA in vitro. SEL results in a significant decrease in the formation of 6-OHDA in vitro, probably as a result of its antioxidant properties. However, the exogenous administration of LD, with or without SEL, either does not lead to the formation of striatal 6-OHDA in vivo or produces concentrations below the detection limit of the assay. This is despite the fact that striatal DA levels in these rats are significantly elevated (two-fold) compared to the control group. The auto-oxidation and monoamine oxidase (MAO)-mediated metabolism of DA causes an increase in the production of superoxide anions in whole rat brain homogenate in vitro. In addition to this, DA is able to enhance the production of hydroxyl radicals by Fenton chemistry (Fe(III)-EDTA/H2O2) in a cell free environment. Treatment with systemic LD elevates the production of striatal superoxide anions, but does not lead to a detectable increase in striatal hydroxyl radical production in vivo. The co-adminstration of SEL with LD is able to prevent the LD induced rise in striatal superoxide levels. It has been found that the presence of DA or 6-OHDA is able to reduce lipid peroxidation in whole rat brain homogenate induced by Fe(II)-EDTA/H2O2 and ascorbate (Fenton system). However, DA and 6-OHDA increase protein oxidation in rat brain homogenate, which is further increased in the presence of the Fenton system. In addition to this, the incubation of rat brain homogenate with DA or 6-OHDA is also accompanied by a significant reduction in the total GSH content of the homogenate. The exogenous administration of LD and/or SEL was found to have no detrimental effects on striatal lipids, proteins or total GSH levels. Systemic LD administration actually had a neuroprotective effect in the striatum by inhibiting iron (II) induced lipid peroxidation. Inorganic studies, including electrochemistry and the ferrozine assay show that DA and 6-OHDA are able to release iron from ferritin, as iron (II), and that DA can bind iron (III), a fact that may easily impede the availability of this metal ion for participation in the Fenton reaction. The binding of iron (III) by DA appears to discard the involvement of the Fenton reaction in the increased production of hydroxyl radicals induced by the addition of DA to mixtures containing Fe(II)-EDTA and hydrogen peroxide. 6-OHDA did not form a metal-ligand complex with iron (II) or iron (III). In addition to the antioxidant activity and MAO-B inhibitory activity of SEL, the iron binding studies show that SEL has weak iron (II) chelating activity and that it can also form complexes with iron (III). This may therefore be another mechanism involved in the neuroprotective action of SEL. The results of the pineal indole metabolism study show that the systemic administration of SEL increases the production of N-acetylserotonin (NAS) by the pineal gland. NAS has been demonstrated to be a potent antioxidant in the brain and protects against 6-OHDA induced toxicity. The results of this study show that DA displays antioxidant properties in relation to lipid eroxidation and exhibits pro-oxidant properties by causing an increase in the production of hydroxyl radicals and superoxide anions, as well as protein oxidation and a loss of total GSH content. Despite the toxic effects of DA in vitro, the treatment of rats with exogenous LD does not cause oxidative stress or oxidative damage. The results also show that LD and SEL have some neuroprotective properties which make these agents useful in the treatment of PD.

Uremic pruritus (UP) arises in end-stage renal disease (ESRD) and is not relieved by proper dialysis. While the pathogenesis of UP is not well understood, UP responds poorly to anti-histamines. We performed a case-control study to test if cutaneous protease-mediated, non-histamine itch is augmented in UP, and if UP is associated with altered epidermal and/or papillary dermal innervation. We recruited 12 hemodialysis subjects with ESRD-specific itch (cases) (Visual Analogue Scale (VAS)-average itch in the preceding week, 78/100), and 13 age- and sex-matched hemodialysis subjects without pruritus (controls) (VAS- average itch in the preceding week, 0/100; p<0.0001 cases vs. controls). Cowhage spicule-induced itch was induced in the back where all subjects exhibited itch, and the entire duration of itch was measured with the general Labeled Magnitude Scale. Subsequently, a punch biopsy was taken from this sensory-tested skin and multi-label immunohistochemistry was performed to measure epidermal and papillary dermal innervation. In cases vs. controls, cowhage-induced area under the curve (AUC) for itch was significantly larger (median, 25%–75%: 175.4, 101.0–252.2 vs. 42.4, 24.0–160; p=0.04) as was perceived peak itch intensity (53.6, 53.3–78.9 vs. 34.2, 20.9–55.6; p=0.02). Cases showed a significant reduction in papillary dermal nerve length (PDNL)/mm epidermis (2295, 1659–2970 vs. 2909, 2228–3523; p=0.003), resulting from the loss of papillary dermal (PD)-calcitonin gene related peptide (CGRP) (+) nerves (p<0.0001), with preservation of %PD-substance P (+) nerves (p=0.1) and intraepidermal nerve fiber density (p=0.1). VAS-average itch in the preceding week negatively correlated with PDNL/mm epidermis (correlation coefficient (CC)=-0.53, p=0.003) and %PD-CGRP (+) nerves (CC=-0.37, p=0.03). Cowhage-induced AUC-itch negatively correlated with %PD-CGRP nerves only in cases (CC=-0.40, p=0.02). Our data suggest augmented protease-dependent signaling contributes to UP and indicate a mechanism for how PD-CGRP (+) nerve loss contributes to UP and augmented cowhage-itch: loss of an afferent skin-derived itch-inhibition signal to the spinal cord dorsal horn. / 2016-10-02T00:00:00Z

No description available.

Dissertation (PhD)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts (obsessions) and repetiti ve mental acts or behaviours (compulsions) . For many years, it was considered a rather uncommon condition, caused by unconscious conflict, and somewhat resistant to treatment. In recent decades, however, it has emerged that OCD is a highly prevalent disorder, mediated by particular neuroanatomical circuits (e.g. striatal pathways) and neurochemical systems (e.g. the serotonin system), and responsive to treatment with serotonin reuptake inhibitors (SRIs) . Nevertheless, many questions remain; about the specificity of neuroanatomical findings to OCD, about the role of the multiple serotonin (5-HT) receptor subtypes (e.g. 5-HT10)' and about the appropriate pharmacotherapy for patients resistent to SRI treatment? In a series of studies, 1) the neuroanatomy of OCD was assessed by means of magnetic resonance imaging and neuropsychological testing, 2) the neurochemistry of OCD was assessed by means of functional brain imaging after administration of a 5-HT10 agonist, and 3) the pharmacotherapy of OCD was explored in a series of treatment-refractory OCD and OCD spectrum disorder patients using SRI augmentation with a dopamine blocker. Although no significant difference was found in the volume of the caudate in women with OCD and controls, there was a significant correlation between caudate volume and neuropsychological dysfunction in patients, consistent with evidence of striatal involvement in OCD. Functional imaging demonstrated behavioural heterogeneity, but brain-behaviour correlations were positive, consistent with preclinical evidence of a role for the 5-HTlD receptor in the mediation of OCD. Finally, preliminary treatment findings with dopamine blocker augmentation of a SRI were promising, consistent with preclinical understandings of the interactions between the dopamine and serotonin systems. Although oeD is a complex disorder, a number of future research avenues hold promise for providing a thorough delineation of its pathogenesis. / AFRIKAANSE OPSOMMING: Obsessief-kompulsiewe steuring (OKS) word gekenmerk deur indringende gedagtes (obsessies) en herhalende gedagtes of gedrag (kompulsies). Vir baie jare is dit beskou as 'n redelik seldsame toestand wat veroorsaak word deur onbewustelike konflik, en wat in 'n mate teen behandeling weerstandig is. Meer onlangs het dit egter na vore getree as 'n toestand wat baie dikwels voorkom, wat deur spesifieke neuroanatomiese siklusse (bv. striatale bane) en neurochemiese sisteme (bv. die serotonien-sisteem) teweeg gebring word, en wat op behandeling met serotonien heropname inhibeerders (SHIs) reageer. Nogtans is daar steeds baie vrae; oor die spesifisiteit van neuroanatomiese bevindinge vir OKS, oor die rol van die veelvuldige serotonien (5-HT) reseptor subtipes (bv. 5- HT1D), en oor die toepaslike farmakoterapie vir pasiënte wat weerstandig is vir SHI behandeling. In' n reeks van navorsingstudies, is 1.) die neuroanatomie van OKS deur middel van magnetiese resonans beelding en neurosielkundige toetse ondersoek, 2. ) die neurochemie van OKS deur middel van funksionele breinbeelding na toediening van 'n 5-HT1D agonis bepaal, en 3.) die farmakoterapie van OKS in 'n reeks van behandelingsweerstandige OKS en OKS-spektrum steuring pasiënte - waar gebruik gemaak is van SHI aanvulling met 'n dopamien-blokker - ondersoek. Alhoewel daar geen beduidende verskil in die volume van die caudata in vroue met OKS en kontroles gevind is nie, was daar 'n beduidende korrelasie tussen die caudata volume en neurosielkundige wanfunksionering in pasiënte, in ooreenstemming met striatale betrokkenheid in OKS. Funksionele beelding het positief, in demonstreer, maar ooreenstemming met brein-gedrag pre-kliniese heterogeneïteit korrelasies was in gedrag bewyse vir 'n rol vir die 5-HT1D reseptor in die bemiddeling van OKS. Ten laaste, voorlopige behandelingsbevindinge oor dopamienblokker aanvulling van 'n SHI is belowend, in ooreenstemming met v

Le LPGi est la région bulbaire qui contient le plus grand nombre de neurones exprimant Fos pendant l’hypersomnie de SP. 10% de ces neurones Fos dans le LPGi projettent au locus coereleus, une région SP-Off. Récemment, Sapin et al. ont montré que 70% des neurones exprimant Fos pendant l’hypersomnie de SP sont de nature GABAergique. Notre hypothèse est que le LPGi contient des neurones de nature SP-On dont une partie participerait à l’inhibition des noyaux SP-Off. Nous cherchons à vérifier cette hypothèse, d’autre part à identifier les régions afférentes au LPGi actives au cours du SP et enfin, à identifier les projections du LPGi. Nous avons utilisé l’enregistrement extracellulaire des neurones du LPGi chez le rat vigile en contention stéréotaxique. Nous avons couplé cette technique avec le protocole de privation/ rebond de SP par la technique de la piscine. L’analyse du taux de décharge des neurones enregistrés au sein du LPGi montre que celui-ci contient trois types neuronaux différents (SP-On, SP-Off et indifférents). L’analyse des données neuroanatomiques montre que l’afférence majeure du LPGi, active au cours du SP, réside dans le SLD. Le LPGi est donc bien impliqué dans le réseau du SP car il contient des neurones faisant varier leur taux de décharge avec les différents états de vigilance. Le SLD, considéré comme la structure exécutive du SP, de nature glutamatergique, exciterait le LPGi au cours du SP. Ce dernier, de nature GABAergique, inhiberait le noyau moteur facial. Ce travail met pour la première fois en évidence l’activité de la voie SLD-bulbe rachidien ventrolatéral et suggère que le LPGi participe en partie à l’atonie musculaire caractéristique du SP / The LPGi is a ventrolateral medullary area that contains the highest number of Fos-labelled neurons during a paradoxical sleep (PS) hypersomnia. Ten % of these Fos neurons project to the locus coeruleus, a PS-Off area and 70% of these Fos neurons are GABAergic. Our hypothesis is that the LPGi contains PS-On neurons involved in the inhibition of the PS-Off nuclei. Our aim was to check this hypothesis by recording the unit activity of the LPGi neurons, by identifying the afferent areas to the LPGi and determining its projection areas activated during PS. We have used extracellular unit recordings in the unanethetized head-restrained rat model and coupled this method to a selective PS deprivation using the flower-pot method. The analysis of the firing rate of the LPGi neurons showed that there are three different groups, SP-On, SP-Off and indifferent neurons. Moreover, the SLD, a PS-On area, is the main afferent to the LPGi activated during PS rebound. Our conclusion is that the LPGi is involved in the network generating PS. The SLD, considered as the PS executive area through glutamatergic neurons, may excite the LPGi during this state. The LPGi, through its GABAergic neurons, may inhibit the facial motor nucleus. This work provides for the first time evidence for a SLD-ventrolateral medulla pathway and suggests that the LPGi participates in the muscular atonia occurring during PS

INTRODUÇÃO: As terapias mais eficazes para zumbido são baseadas nos modelos psicológico e neurofisiológico, que teorizam que o incômodo existente é resultado da interação dinâmica dos centros auditivos, sistemas límbico e nervoso autônomo. Embora sejam amplamente aceitos na prática clínica, ainda necessitam validação científica. A ressonância magnética funcional (RMf) é um método objetivo capaz de identificar as áreas cerebrais descritas pelos modelos, como também a rede neural relacionada à percepção de estímulos emocionais, que ainda não foi investigada em estudos de zumbido. OBJETIVOS: 1) Baseado nos modelos que explicam o incômodo do zumbido, analisar as áreas corticais auditivas e não-auditivas em adultos normo-ouvintes com e sem zumbido, ativadas durante estimulação auditiva desagradável; 2) de acordo com a teoria da percepção de um estímulo emocional, avaliar se os pacientes com zumbido recrutavam a mesma rede neural para a percepção de sons desagradáveis que os indivíduos sem zumbido. MÉTODOS: Quinze pacientes com zumbido subjetivo crônico não-pulsátil (grupo zumbido, GZ) e 20 voluntários sem zumbido (grupo controle, GC), pareados por sexo e idade, foram submetidos à RMf (1.5 T). Os critérios de inclusão foram: indivíduos destros, audiometria normal, inventário de depressão de Beck < 20 pontos e escolaridade equivalente ao segundo grau completo. O paradigma incluiu sons do catálogo IADS (International Affective Digitized Sounds), validados para valência emocional e grau de estímulo, associado à escala análogo-visual SAM (Self Assessment Manikin), modificada para RMf. O paradigma foi praticado previamente em um simulador de RMf. A aquisição de imagens e a apresentação de estímulos foram realizadas através da técnica de seqüência de pulso com ruído acústico minimizado (SPRAM). RESULTADOS: O hipocampo esquerdo foi a área mais ativada no GC e não demonstrou atividade neural no GZ, no qual a maior ativação foi localizada na ínsula esquerda. Áreas auditivas (giro temporal superior e região ínfero-posterior do lobo temporal) e límbicas (ínsula) foram ativadas pelos sons desagradáveis em ambos os grupos. Na análise comparativa, a maior ativação no GZ ocorreu no cerebelo direito (p < 0,05) e, no GC, no giro temporal superior esquerdo e giro frontal inferior esquerdo (p < 0,05). CONCLUSÕES: A ativação paralela dos sistemas auditivo e límbico aos sons desagradáveis foi demonstrada nos pacientes com e sem zumbido. Entretanto, na comparação entre grupos, áreas límbicas e préfrontais não foram significantemente mais ativadas em pacientes com zumbido. Sugere-se que o cerebelo direito, recentemente relacionado à função cognitiva, pode ser a área não-auditiva envolvida no incômodo do zumbido. Especula-se que o incômodo do sintoma esteja relacionado a anormalidades na percepção emocional, seja pela identificação exacerbada (via ínsula) de sons desagradáveis ou pela ausência de regulação da resposta afetiva (via hipocampo) a este estímulo / INTRODUCTION: The most successful tinnitus therapies are based on the psychological and the neurophysiological models, which suggest that tinnitus-related annoyance results from the dynamic interaction of auditory brain centers, limbic and autonomic nervous systems. Although these models have been largely accepted in clinical practice, they lack experimental support and validation. Functional magnetic resonance imaging (fMRI) offers the opportunity to identify those brain regions pertinent to each model, and studies the neural network involved in the theory of emotion perception of stimuli. The latter has not been thoroughly investigated in tinnitus. OBJECTIVES: 1) Based on the models of developing tinnitus-related annoyance, analyze the cortical areas (auditory and non-auditory) in normal hearing individuals with and without tinnitus, activated by unpleasant auditory stimulation; and 2) according to the theory of emotion perception of acoustic stimulus, evaluate whether the patients with tinnitus were using the same neural network for perception of unpleasant sounds than the subjects without tinnitus. METHODS: Fifteen subjects with chronic subjective non-pulsatile tinnitus (tinnitus group, TG), and 20 healthy volunteers (control group, CG), matched for gender and age, were submitted to 1.5 T fMRI. Inclusion criteria consisted of normal pure-tone audiogram, righthandedness, Beck depression inventory < 20 points, and formal education level > 11 years. The paradigm comprised sounds from IADS (International Affective Digitized Sounds) with validated emotional valence and arousal, and a modified visual-analog Self Assessment Manikin (SAM) scale. All individuals previously practiced the task in a mock scanner. Image acquisition and stimuli presentation were designed using the silent event-related method, in which the scanner acoustic noise effects were minimized during brain activation detection. RESULTS: The left insula presented the highest neuronal activity in the TG, which showed no activity in the hippocampus. In the CG, the activation was markedly present in the left hippocampus, and was barely found in the insula. Unpleasant sounds activated auditory areas (superior temporal gyrus, inferior-posterior temporal lobe) and the limbic system (insula) in both groups. When the groups were compared, the right cerebellum was the most activated brain area in the TG (p < 0.05), and CG showed the highest activation in the left superior temporal gyrus and the left inferior frontal gyrus (p < 0.05). CONCLUSIONS: Parallel activation of auditory and limbic systems was demonstrated in both tinnitus and control patients. However, limbic and prefrontal areas were not significantly more activated in patients with tinnitus. The right cerebellum, recently described to have cognitive function, may be responsible for integrating the brain centers involved in the annoyance of tinnitus. In addition, we suggested that tinnitus-related annoyance may be secondary to emotion perception abnormalities, either a higher identification of emotional significance of the unpleasant sounds (via insula), or a lack of regulation of individual affective reaction (via hippocampus)