MRI provides a powerful tool to investigate brain structure in living humans. However a major challenge is interpreting the biological underpinnings of changes at this scale. This dissertation describes investigations into the problem of linking microscale post mortem cortical cytoarchitecture with millimeter-scale measures of cortical anatomy accessible through in vivo MRI. Chapter 1 introduces the problem and previous work done to address it. The following two chapters apply classical atlases of cortical cytoarchitecture to understanding morphological changes both in health (Chapter 2) and in disease (Chapter 3). Chapter 2 demonstrates that sensory processing hierarchies exhibit increasing gradients of cortical thickness, related to changes in cortical cytoarchitecture. In Chapter 3, cytoarchitectonically described differences in gyral and sulcal laminar structure were used to create markers of laminar change from MRI changes in schizophrenia. Classical measurements of histology have limitations; they are observer dependent, two-dimensional with limited coverage of the cortex. To address these issues, Chapters 4-6 document work carried on BigBrain, a 3D 20$\mu$m resolution histological dataset. I created a high-resolution 3D atlas of laminar cytoarchitecture, which was mapped to MRI-compatible cortical surface reconstructions. Chapter 4 records the development of an automated 1D profile-based approach to laminar analysis, revealing basic principles of cortical cytoarchitecture. In Chapter 5 this approach was extended to identify 6 cortical layers throughout the isocortex. These tools can be used to segment 1D cortical intensity profiles derived from any modality. In Chapter 6, the analysis of cortical gradients initially identified using MRI cortical thickness in Chapter 2 was replicated and extended using novel histological data. First histological cortical thicknesses were tested for the same patterns organization measured on in vivo MRI in Chapter 2. These analyses were extended to test which layers contributed most to overall thickness. High-resolution, complete maps of cortical cytoarchitecture mapped to MRI-template cortical surface reconstructions, are a powerful tool and dataset for the neuroimaging community. They offer new possibilities for linking cortical microstructure to in vivo neuroimaging.

The nervous system and immune system contact one another through two-way communication in order to establish and preserve homeostasis. The sympathetic neurotransmitter norepinephrine has an impact on how the immune system responds by affecting regional blood flow and activation of adrenergic receptors on leukocytes. Former studies showed that immune cells are capable of releasing nerve growth factor allowing for the establishment and continuation of sympathetic nerves in targeted tissues. From this gathered information, it was hypothesized that sympathetic nerves would prove to be less frequent in spleens from the immunodeficient R2G2 mouse strain (Envigo) when compared to 129P3/J (129) and C57BL/6 (C57) strains. R2G2 mice are an immunodeficient strain that lacks functional T, B, and natural killer cells. Ten to eleven week aged-matched male mice were measured by body weight, spleen weight, and temperature. Spleens were cut and fixed for histological investigation. Sympathetic nerves were labeled by immunostaining tyrosine hydroxylase (TH). Hematoxylin & eosin (H&E) was used to stain spleen sections in order to evaluate cytoarchitecture. Von Willebrand factor (VWF) was used to immunostain for megakaryocytes. R2G2 mice showed slightly higher temperatures and body weights but yielded a significantly smaller spleen weight (R2G2, 38.20 ± 1.48; 129, 65.08 ± 11.71; C57, 81.33 ± 8.38; P< 0.0001, ANOVA). TH stain revealed sympathetic innervation in all strains but location and morphology differed in R2G2 mice compared to controls. Control spleens had nerves which entered white pulp regions of the spleen and were closely related to leukocytes. Fiber profiles in the controls were filamentous with small acute bends. R2G2 differed by having (TH+) nerve fibers more associated with arteries and less localized in the surrounding parenchyma. The fibers were abnormally swollen and held a more granular shape instead of a filamentous shape. The H&E stain showed clear red and white pulp zones in the control spleens with 129 showing more distinct germinal centers than C57. R2G2 H&E sections showed cytoarchitecture with indistinct pulp areas. VWF staining revealed R2G2 mice had an abundant amount of megakaryocytes versus control mice megakaryocyte counts (R2G2, 11.28 ± 3.87 per 20X field; 129, 1.73 ± 0.70; C57, 1.42 ± 0.13; P< 0.0001, ANOVA) and extramedullary hematopoiesis was highly prominent. This evidence supports that leukocytes secrete neurotrophic factors or are vital to establishing normal growth of TH+ nerves toward the white pulp. Leukocytes may not be required for sympathetic innervation of blood vessels in the spleen, however, lack of leukocytes shows TH+ nerve fibers with abnormal morphology in severely immune threatened mice.

L’ambition des très hauts champs magnétiques (≥ 7T) à forts gradients (≥ 300mT/m) est de dépasser la résolution millimétrique imposée à plus bas champ pour atteindre l’échelle mésoscopique en neuroimagerie. Etudier le cerveau à cette échelle est essentiel pour comprendre le lien entre fonction et substrat anatomique. Malgré les progrès réalisés sur les aimants cliniques à 7T, il n’en est pas de même des gradients. Cette thèse vise à cartographier le cerveau humain à l’échelle mésoscopique via l’étude de pièces anatomiques post mortem. Une approche alternative a été choisie, reposant sur l'utilisation d'imageurs précliniques à très hauts champs (7T et 11.7T) et forts gradients (780mT/m). Après une première étape de préparation (extraction et fixation) opérée au CHU de Tours, une pièce anatomique complète a été scannée à 3T, avant découpe de l’hémisphère gauche en sept blocs. Un protocole d’acquisition IRM ciblant une résolution mésoscopique a ensuite été mis en place à 11.7T. Ce protocole, incluant des séquences anatomiques, relaxométriques, et de diffusion, a été validé à l’aide de deux structures clé: un hippocampe et un tronc cérébral. Les données anatomiques et de diffusion acquises à une résolution mésoscopique sur l’hippocampe ont permis de segmenter ses sous-champs, d’extraire le circuit polysynaptique et d’observer l’existence d’un gradient de connectivité et de densité neuritique positif dans la direction postéro-antérieure de l’hippocampe. L’utilisation de modèles avancés d’étude de la microstructure a également révélé l’apport de ces techniques pour la segmentation de l’hippocampe, les cartes de densité neuritique révélant les trois couches des champs ammoniens. Un tronc cérébral a ensuite été scanné, avec une résolution atteignant la centaine de micromètres. Une segmentation de 53 de ses 71 noyaux a été réalisée au sein du CHU de Tours, permettant d’établir la cartographie IRM du tronc cérébral humain la plus complète à ce jour. Les principaux faisceaux de la substance blanche ont été reconstruits, ainsi que les projections du locus coeruleus, structure connue pour être atteinte dans le maladie de Parkinson. Forts de ces résultats, la campagne d'acquisition de l'hémisphère gauche, d’une durée de 10 mois, a été initiée. Le protocole d’acquisition à 11.7T intègre des séquences anatomiques (100/150µm) ainsi que des séquences d'imagerie 3D pondérées en diffusion (b=1500/4500/8000 s/mm², 25/60/90 directions) à 200µm. Des acquisitions complémentaires réalisées à 7T comprenant des séquence d’écho de spin rapide avec inversion-récupération ont par ailleurs permis d’étudier la myéloarchitecture du cortex cérébral et d’identifier automatiquement sa structure laminaire. Un nouveau modèle de mélange de Gaussiennes a été développé, intégrant les informations myéloarchitecturales issues de la cartographie T1 et les informations cytoarchitecturales issues de l’imagerie de diffusion. Il a ainsi pu être démontré que l’utilisation conjointe de ces deux informations permettait de mettre en évidence des couches du cortex visuel, l’information myéloarchitecturale favorisant l’extraction des couches externes et la densité neuritique celle des couches plus profondes. Enfin, l’exploitation des données IRM acquises à 11.7T sur les différents blocs a nécessité la mise en place d’une chaîne de prétraitements pour corriger les artéfacts d’imagerie et reconstruire l’hémisphère entier à l’aide de stratégies de recalage difféomorphe avancées. L’objectif de ce projet est l’obtention d’un jeu de données IRM de très haute résolution spatio-angulaire de l’hémisphère gauche. Ce jeu de données anatomique et de diffusion unique permettra à terme de constituer un nouvel atlas IRM mésoscopique de la structure, de la connectivité et de la cytoarchitecture du cerveau humain. / The aim of ultra-high field strength (≥7T) and ultra-strong gradient systems (≥300mT/m) is to go beyond the millimeter resolution imposed at lower field and to reach the mesoscopic scale in neuroimaging. This scale is essential to understand the link between brain structure and function. However, despite recent technological improvements of clinical UHF-MRI, gradient systems remain too limited to reach this resolution. This thesis aims at answering the need for mapping the human brain at a mesoscopic scale by the study of post mortem samples. An alternative approach has been developed, based on the use of preclinical systems equipped with ultra-high fields (7T/11.7T) and strong gradients (780mT). After its extraction and fixation at Bretonneau University Hospital (Tours), an entire human brain specimen was scanned on a 3T clinical system, before separating its two hemispheres and cutting each hemisphere into seven blocks that could fit into the small bore of an 11.7T preclinical system. An MRI acquisition protocol targeting a mesoscopic resolution was then set up at 11.7T. This protocol, including anatomical, quantitative, and diffusion-weighted sequences, was validated through the study of two key structures: the hippocampus and the brainstem. From the high resolution anatomical and diffusion dataset of the human hippocampus, it was possible to segment the hippocampal subfields, to extract the polysynaptic pathway, and to observe a positive gradient of connectivity and neuritic density in the posterior-anterior direction of the hippocampal formation. The use of advanced microstructural models (NODDI) also highlighted the potential of these techniques to reveal the laminar structure of the Ammon’s horn. A high resolution anatomical and diffusion MRI dataset was obtained from the human brainstem with an enhanced resolution of a hundred micrometers. The segmentation of 53 of its 71 nuclei was performed at the Bretonneau University Hospital, making it the most complete MR-based segmentation of the human brainstem to date. Major white matter bundles were reconstructed, as well as projections of the locus coeruleus, a structure known to be impaired in Parkinson’s disease. Buoyed by these results, a dedicated acquisition campaign targeting the entire left hemisphere was launched for total scan duration of 10 months. The acquisition protocol was performed at 11.7T and included high resolution anatomical sequences (100/150μm) as well as 3D diffusion-weighted sequences (b=1500/4500/8000 s/mm², 25/60/90 directions, 200μm). In addition, T1-weighted inversion recovery turbo spin echo scans were performed at 7T to further investigate the myeloarchitecture of the cortical ribbon at 300µm, revealing its laminar structure. A new method to automatically segment the cortical layers was developed relying on a Gaussian mixture model integrating both T1-based myeloarchitectural information and diffusion-based cytoarchitectural information. The results gave evidence that the combination of these two contrasts highlighted the layers of the visual cortex, the myeloarchitectural information favoring the extraction of the outer layers and the neuritic density favoring the extraction of the deeper layers. Finally, the analysis of the MRI dataset acquired at 11.7T on the seven blocks required the development of a preprocessing pipeline to correct artifacts and to reconstruct the entire hemisphere using advanced registration methods. The aim was to obtain an ultra-high spatio-angular resolution MRI dataset of the left hemisphere, in order to establish a new mesoscopic post mortem MRI atlas of the human brain, including key information about its structure, connectivity and microstructure.

Environmental events simultaneously transduced by more than one sensory modality underlie multisensory processing in the CNS. While most studies of multisensory processing examine functional effects, none have evaluated the influence of local or columnar circuitry. The goal of the present study is to examine of local features of the ferret lateral rostral suprasylvian sulcus (LRSS), a multisensory cortex. Immunostaining revealed the cytoarchitectonic features of the LRSS: thick supragranular layers, a narrow layer IV, and moderately stained but differentiated infragranular layers. Golgi-Cox techniques were used with light microscopy and digital reconstruction to document neuronal morphology. Among the 90 reconstructed neurons, 4 distinct forms or pyramidal and 2 types of non-pyramidal neurons were found. Measurement of maximal dendritic spread indicates that a cortical column in the LRSS was 250.9 um in diameter. These results describe local features of the LRSS upon which future experiments of intrinsic circuitry will be based.

The subject of the thesis is a study of the projections from low threshold oral and face afferents to the cerebral cortex and of descending motor control mechanisms originating in the cerebral cortex or the hypothalamus and influencing the jaw reflexes.Cats anaesthetized with chi oral ose were used for the experiments. Ipsi- and contralateral nerves from the oral cavity and the face were stimulated electrically. Cortical potentials were averaged and recorded. The location of the projections was related to the cytoarchi-tectonic areas of the cerebral cortex. It was found that the afferents projected to separate maximum points in areas 3a, 3b, 5a and 6aß. The projections to areas 3a and 3b were somatotopically organized, but the layout of the projections on the cortex was not facelike.The effect of monopolar anodal stimulation of the cerebral cortex on the monosynaptic jaw closing and the di synaptic jaw opening reflexes was investigated. A sequence of facilitation and inhibition of both reflexes was elicited by cortical stimulation. The effects were of short latency (2.5 ms) and could start with either facilitation or inhibition. The timecourse of the sequence was sinuslike with a period of 10 ms. The largest effect originated in the "sensory" areas 3a and 3b and not in the "motor" areas 4y and 6ag. It is suggested, that a tri gemino-cortico-tri geminai loop via area 3a may function in reflex modulation of jaw movements.The hypothalamic effects on the jaw reflexes were evoked by electrical stimulation in those parts of the hypothalamus, which are w known to generate defence, attack or feeding responses. A tenfold facilitation of the jaw closing reflex and a facilitation followed by almost complete inhibition of the jaw opening reflex were observed in the anaesthetized animal with intact cerebral cortex. The effects remained but were diminished in amplitude after cortical ablation. The descending path was located in the ventral midbrain tegmentum.It is suggested that the observed hypothalamo-tri geminai mechanism may exercise a tonic influence on the trigeminal motoneurones, thereby controlling the set points of the biting force and the rest position. The implications of this hypothesis on the etiology of bruxism and the myofascial pain-dysfunction are discussed. / <p>Härtill 3 rapporter.</p> / digitalisering@umu

Doctor Scientiae / The blood-brain barrier (BBB) is a restrictive interface located between the blood circulation and the central nervous system (CNS), regulating the homeostatic environment of the neuronal milieu, by controlling the permeability of the cerebrovasculature. Currently, we cannot fully comprehend the regulatory features and the complexity of BBB morphology to allow for intervention clinically. The thesis consists of four publications. The methodology paper proposes a novel experimental design to visualize the morphological architecture of immortalized mouse brain endothelial cell lines (bEnd3/bEnd5). The brain endothelial cells (BECs) were grown on cellulose matrices and fixed in 2.5 % glutaraldehyde in preparation for visualization of the paracellular (PC) spaces between adjacent BECs, employing high-resolution electron microscopy (HREM), with vested interest in the morphological profile of the developing BEC. The second publication addresses and reports on the nanosized detail of BEC monolayer morphology utilizing high-resolution scanning electron microscopy (HR-SEM) and published the first descriptions of the extrusion of a basement membrane from developing in vitro BECs. Moreover, we categorized and discussed two types of nanotubule (NT) development specific for the establishment of the BEC monolayers. NTs can occur via nanovesicle extrusion onto the BEC membrane surfaces, which fuse, forming tunneling NTs (TUNTs) between adjacent BECs. Furthermore, cytoplasmic extensions of BEC membrane leading edges give rise to tethering NT (TENTs), which result in overlapping regions across the PC spaces, resulting in PC occlusion. BEC NT communication is illuminated in a third publication utilizing immunofluorescence microscopy, which reports on the molecular, cytoskeletal elements governing NT formation. This study shows, for the first time, f-actin and α-tubulin cytoskeletal proteins extending between the soma of the cells and NT cytoskeletal structures within an in vitro BBB model. Thereafter, the effects depolymerizing agents, Cytochalasin D and Nocodazole, were investigated on f-actin and α-tubulin cytoskeletal protein generation,functionality of NT morphology, cell division and permeability. For the first time, we show that f-actin possesses an additional function, key to tight junction, plaque protein organization. Moreover, it facilitates TENT formation, essential for cytoplasmic projection across PC spaces. Conversely, α-tubulin facilitates known functions: (i) transportation, (ii) cytokinesis, (iii) cellular division, and (iv) possesses a novel function as the molecular cytoskeletal backbone of TENTs, which facilitates BBB impermeability. A critical review evaluates past literature, in light of the current findings emanating from this study. The review critiques the concept of BEC cilia, which have been reported in the literature, comprised of tubulin and actin, but at low-resolution. In the light of our novel observations, nowhere in transmission electron microscopy do we observe cilia on the BECs, we postulate that NTs have been misnamed and mischaracterized as cilia. The thesis endeavors to elucidate the complexity of BEC nanostructures by examining the emerging role of the nanoscopic landscape of BBB development and the changing nature of BEC morphology, NT formation and associated cytoarchitectural underpinnings governing NT morphology. The research study attempts to, with a view to create new avenues for treating brain pathology, revolutionize our interpretation of barrier-genesis on a nanoscale.

A novel method is presented for analyzing fMRI data, which relies on probabilistic estimates of microanatomically defined regions in individual fMRI volunteers. Postmortem structural and cytoarchitectonic information from the Julich/Dusseldorf group in Germany is aligned to the high-resolution structural MR images of functional MRI volunteers. This is achieved using nonlinear registration, which is applied only to the region of interest. The registered postmortem datasets are then combined into probability maps for microanatomically defined regions that are tailored to the anatomy of individual fMRI volunteers. These are then used as weighted spatial filters on functional MR data. In this thesis, three regions of the primary auditory cortex (located on Heschl's gyrus) have been targeted, and the analysis method is used to explore how these three areas respond to different kinds of sound. Regions Te1.0 and Te1.2 both demonstrate pitch sensitivity, consistent with published observations of the functional response of homologous regions in nonhuman primates. Area Te1.1 displayed sensitivity to both noise and pitch, consistent with the theory that it is homologous with the microanatomically similar area CM in nonhuman primates. Furthermore, the custom probability maps are much less diffuse and anatomically more precise than previous versions generated using the same postmortem data, and therefore permit a more sensitive and anatomically precise analysis of functional activity. This method could be applied to any other microanatomically defined region that has been characterized in the Julich postmortem dataset. / Thesis (Master, Computing) -- Queen's University, 2008-09-26 19:50:54.582

Made available in DSpace on 2014-12-17T15:37:05Z (GMT). No. of bitstreams: 1 RayaneBSN_DISSERT.pdf: 693632 bytes, checksum: a22430e8639b4b9e576ca8573f8e7d9d (MD5) Previous issue date: 2011-08-03 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The suprachiasmatic nucleus (SCN) of the anterior hypothalamus, together with the intergeniculate leaflet (IGL) of the thalamus are considered the central components of the circadian timing system (CTS) of mammals. This system is responsible for the generation and regulation of circadian rhythms by establishing a temporal organization of physiological processes and behaviors. The neuronal specific nuclear protein (NeuN) has been widely used as a neuronal marker in several studies. Since glial fibrillary acidic protein (GFAP) is a component of intermediate filaments found in the cytoplasm of astrocytes and is commonly used as a specific marker for these cells. This study aims to identify, in the marmoset, the NeuN immunoreactive neurons and glial cells immunoreactive to GFAP, as well as map the major route of photic synchronization of the STC, retinohypothalamic tract (RHT), and identify the indirect pathway to the SCN and pregeniculate nucleus (PGN) - structure homologous to IGL rodents, using immunohistochemical and cytoarchitectonic techniques. Observed in SCN the presence of neurons immunoreactive to NeuN and terminals immunoreactive subunit b of cholera toxin (CTb), neuropeptide Y (NPY) and serotonin (5- HT). In the PGN noted the presence of the NeuN and NPY immunoreactive neurons and the immunoreactive terminals CTb and 5-HT. Astrocytes are present throughout the extent of the SCN and the PGN this New World primate / O n?cleo supraquiasm?tico (NSQ) do hipot?lamo anterior, juntamente com o folheto intergeniculado (FIG) do t?lamo s?o considerados os componentes centrais do sistema de temporiza??o circadiana (STC) de mam?feros. Tal sistema ? respons?vel pela gera??o e regula??o dos ritmos circadianos estabelecendo uma organiza??o temporal dos processos fisiol?gicos e comportamentos. A prote?na nuclear neuronal espec?fica (NeuN) tem sido amplamente utilizada como um marcador neuronal em diversos estudos. J? a prote?na ac?dica fibrilar glial (GFAP) ? um componente dos filamentos intermedi?rios encontrada no citoplasma dos astr?citos e ? comumente usada como um marcador espec?fico para essas c?lulas. Este trabalho tem como objetivo identificar, no sagui, neur?nios imunorreativos a NeuN e c?lulas gliais imunorreativas a GFAP, bem como mapear a principal via de sincroniza??o f?tica do STC, o trato retinohipotal?mico (TRH), e identificar as vias indiretas para o NSQ e n?cleo pr?-geniculado (NPG) estrutura hom?loga ao FIG dos roedores, utilizando t?cnicas citoarquitet?nica e imunoistoqu?mica. Observamos no NSQ a presen?a de neur?nios imunorreativos a NeuN, bem como terminais imunorreativos a subunidade b da toxina col?rica (CTb), a neuropept?do Y (NPY) e a serotonina (5-HT). J? no NPG notamos a presen?a de neur?nios imunorreativos a NeuN e a NPY e terminais imunorreativos a CTb e a 5-HT. Os astr?citos est?o presentes em toda a extens?o do NSQ e do NPG deste primata do Novo Mundo

Made available in DSpace on 2014-12-17T15:36:53Z (GMT). No. of bitstreams: 1 FrancimarAS.pdf: 4205737 bytes, checksum: a4c2113c8c56b274ed7600ae2a39f704 (MD5) Previous issue date: 2008-09-26 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The auditory system is composed by a set of relays from the outer ear to the cerebral cortex. In mammals, the central auditory system is composed by cochlear nuclei, superior olivary complex, inferior colliculus and medial geniculate body. In this study, the auditory rombencephalic centers, the cochlear nuclear complex and the superior olivary complex were evaluated from the cytoarchitecture and neurochemical aspects, thorough Nissl staining and immunohistochemical techniques to reveal specific neuron nuclear protein (NeuN), glutamate (Glu), glutamic acid decarboxilase (GAD), enkephalin (ENK), serotonin (5-HT), choline acetyltransferase (ChAT) and calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). The common marmoset (Callithrix jacchus), a little native primate of the Brazilian atlantic forest was used as an experimental animal. As results, it was noted that the cochlear nuclear complex is composed by anteroventral, posteroventral and dorsal nuclei, and the superior olivary complex is constituted by the lateral and medial superior olivary nuclei and the trapezoid body nucleus. Glu, GAD, ENK, ChAT, CB, CR, PV-immunoreactive cells, fibers and terminals besides besides only 5-HT terminals were found unhomogeneously in all nuclei, of both complex. The emerging data are discussed in a comparative and functional context, and represent an important contribution to knowledge of the central auditory pathways in the common marmoset, and then in primates / O sistema auditivo compreende uma s?rie de esta??es que se estendem desde a orelha externa at? o c?rtex cerebral. Em mam?feros o sistema auditivo central subcortical ? formado essencialmente por n?cleos cocleares, complexo olivar superior, col?culo inferior e corpo geniculado medial. Neste estudo, os centros rombencef?licos, compreendendo o complexo nuclear coclear e o complexo olivar superior foram avaliados com rela??o a sua citoarquitetura e conte?do neuroqu?mico de corpos celulares e terminais ax?nicos, atrav?s das t?cnicas de colora??o de Nissl e imuno-histoqu?mica para prote?na nuclear neur?nio espec?fica (NeuN), glutamato (Glu), descaboxilase de ?cido glut?mico (GAD), encefalina (ENK), serotonina (5-HT), colina acetiltransferase (ChAT) e prote?nas ligantes de c?lcio calbindina (CB), cal-retinina (CR) e parvalbumina (PV). Foi utilizado como animal experimental o sag?i (Callithrix jacchus), um pequeno primata nativo da Mata Atl?ntica do Nordeste Brasileiro. Como resultados, foi evidenciado que o complexo nuclear coclear ? composto pelos n?cleos cocleares antero-ventral, p?stero-ventral e dorsal, e o complexo olivar superior pelos n?cleos olivares superiores lateral e medial e o n?cleo do corpo trapez?ide. Em todos os n?cleos, de ambos os complexos, foram encontrados de forma vari?vel corpos celulares, fibras e terminais imunorreativos a Glu, GAD, ChAT, CB, CR, PV, corpos celulares e terminais imunoreativos a ENK, al?m de fibras e terminais imunorreativos a 5-HT em diferentes densidades. Os dados obtidos s?o discutidos dentro de um contexto comparativo e funcional e representam uma importante contribui??o ao conhecimento das vias auditivas centrais no sag?i, e por extens?o em primatas

Made available in DSpace on 2014-12-17T15:37:21Z (GMT). No. of bitstreams: 1 PauloLAGM_DISSERT.pdf: 1515778 bytes, checksum: c044dde7997a56896121bcf83cf26e6b (MD5) Previous issue date: 2014-03-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The Zona Incerta (ZI) is embryologically derived from the ventral thalamus, in continuity with the reticular nucleus of the thalamus. Studies usingneural tracers technics have allowed identify a complex connectional map including the ZI. Futhermore, cytochemical, molecular and functional data have shown abundant variability in the neurochemical contend in the ZI, as well as,the involvement of the ZI in the modulation of nociception, attention, alertness, control and maintenance of posture and control of visceral activity. This work aims to characterize the cytoarchitecture, neurochemical content of the ZI in the rock cavy (Kerodon rupestris), and a direct retinal-ZI pathway present in this species. The Nissl staining is effective for the delineation and characterization of ZI citoarchitecture. ZIc receives a contralateral retinal projection showing varicosities, suggesting a modulatory character of photic information. The ZI in the rock cavy, as in others rodents and primates, is characterized by a complex neurochemical signature. The ZI neurochemistry presents great diversity, especially in the medial portion of ZIr, where we have found immunoreactivity of all neuroactive substances investigated, and that NOS-IR, GFAP and CR helped the delimitation of middle ZI in ZId and ZIv. Nevertheless, just 5-HT-IR fibers are present in all subdivisions of the ZI. These data demonstrate the great wealth of the neurochemistry of rock cavy s ZI and a direct retinal modulation in the ZI, helping to explain it s broad functional repertory / A Zona Incerta (ZI) ? um grupamento neuronal embriologicamente derivado do t?lamo ventral, em continuidade com o n?cleo reticular do t?lamo. Diversos estudos com tra?adores retr?grados e anter?grados revelaram a conex?o da ZI com diversas estruturas do sistema nervoso central. Dados moleculares e citoqu?micos revelaram que a ZI ? um dos grupamentos neuronais com maior diversidade neuroqu?mica e citoarquitet?nica do dienc?falo, e estudos hodol?gicos e neuroqu?micos permitiram considerar o envolvimento da ZI em diversas fun??es, as quais se destacam a nocicep??o, aten??o, estado de alerta, controle e manuten??o da postura e controle da atividade visceral. Este trabalho tem por objetivo caracterizar a citoarquitetura e o conte?do neuroqu?mico da ZI do moc? (Kerodon rupestris), bem como a afer?ncia ?ptica presente neste n?cleo nesta esp?cie. A t?cnica de Nissl ? eficiente para a delimita??o e caracteriza??o citoarquitet?nica da ZI do moc?; A ZIc recebe proje??o da retina contralateral, apresentando fibras Classe II ou modulator, sugerindo um car?ter modulat?rio da informa??o f?tica; A ZI do moc?, assim como em outros roedores e primatas, ? caracterizada por uma complexa rede neuroqu?mica, sobretudo na por??o medial da ZIr, onde encontramos imunorreatividade de todas as subst?ncias neuroativas investigadas, al?m de que A IR-NOS, GFAP e CR auxiliaram a delimita??o da ZI no n?vel m?dio em ZId e ZIv. Contudo, somente fibras IR 5-HT est?o presentes em todas as subdivis?es da ZI. Esses dados demonstram a grande riqueza neuroqu?mica da ZI do moc?, auxiliando para explicar o envolvimento em um amplo repertorio funcional