The mammalian neocortex is an exquisite, highly organized brain structure composed of hundreds of subpopulations of neurons and glia, precisely connected to enable motor control, sensory perception, information integration, and planning. Unique molecular, structural, and anatomical neuronal properties underlie diverse functionality, endowing much of the neocortex’s complex processing power. Neocortical size correlates with information processing capacity, suggesting that increased neuronal number and diversity begets increased sophistication. One excitatory projection neuron type, callosal projection neurons (CPN), has disproportionately expanded with cortical size increase. CPN directly connect homotypic regions of the two neocortical hemispheres by sending axons via the largest white matter fiber tract in the brain, the corpus callosum (CC), allowing quick relay, integration, and comparison of information. In humans, the CC contains over 300,000 axons, CPN have been centrally implicated in autism spectrum disorders, and absence or surgical disruption of CPN connectivity in humans is associated with defects in abstract reasoning, problem solving, and generalization. Therefore, CPN are critical to complex brain functions, and their diversity likely contributes to these roles. Work presented in this dissertation addresses molecular controls over CPN development, specifically genes that are expressed by, and function in, particular subpopulations of CPN. While much progress has been made in identifying molecular controls over neocortical arealization, lamination, and broad subtype specification, CPN diversity has remained largely unaddressed. Therefore, this work begins by identifying genes more highly expressed in CPN than other closely related projection neuron populations, and uncovers molecular diversity within CPN. From this molecular diversity, functional analysis of three candidate molecular controls over CPN subtype diversity follows. Cited2 acts broadly in neocortical progenitor development and postnatally in refining somatosensory CPN identity. Caveolin1 identifies a population of CPN with dual axonal projections. Tmtc4 is mutated in human CC disease and can function in CPN axonal development. These analyses of CPN molecular diversity in mouse then expand to an investigation of which molecular subpopulations are conserved, expanded, or uncommon between rodent and primate, allowing both for comparative evolutionary theories of CPN function, and indicating which CPN populations critical for human brain function can be best studied in rodent models.

Plusieurs fonctions cognitives sont latéralisées dans le cerveau humain adulte. Nous avons étudié l’origine des asymétries fonctionnelles chez les nourrissons, en évaluant les substrats neuronaux de reconnaissance des visages et des traitements du langage imbriqués dans les réseaux visuels et auditifs, grâce à la neuroimagerie non invasive (EEG et l’IRM de diffusion). Pour cela, nous avons étudié le développement fonctionnel et structurel de ces deux systèmes cérébraux au cours des six premiers mois postnataux. Nous avons observé que la vitesse des réponses visuelles était liée à la maturation des faisceaux de fibres de la matière blanche conduisant ces réponses, plus que l’âge des bébés, alors que la vitesse des réponses auditives doit dépendre d’un réseau de faisceaux de fibres et de régions corticales plus vaste. Parallèlement, nous avons étudié la latéralisation de la reconnaissance des visages grâce à un paradigme de discrimination des visages présentés dans chaque hémichamp. Nous avons observé que seul l'hémisphère droit pouvait discriminer les visages et que les informations pertinentes étaient transférées entre les deux hémisphères. Pour cibler la latéralisation du traitement du langage, nous avons étudié les réponses à des stimuli de la parole présentés de manière monaurale. Une comparaison entre un groupe de nourrissons avec une agénésie du corps calleux et un groupe contrôle a montré que les réponses à ces stimuli étaient transférées de façon asymétrique via le corps calleux. Cette asymétrie, facilitée vers l’hémisphère gauche, intervient probablement dans la latéralisation précoce du réseau du langage. L’ensemble de ces études mettent bien en évidence le potentiel de la neuroimagerie pour étudier le développement du cerveau et ces asymétries précoces. / Several cognitive functions such as face and speech processing are lateralized in the adult human brain. The ontogeny of these functional asymmetries is yet poorly understood. We aimed to evaluate the neural substrates of face and speech processing, nested in the visual and auditory networks using non-invasive neuroimaging techniques in infants. First, we studied how the functional and structural characteristics of these two brain systems change over the first postnatal semester. With EEG, we showed age-related decreases in the latency of brain responses and demonstrated that the speed of early visual responses is related to the maturation of underlying white matter tracts conducting them, as assessed with diffusion MRI. For the auditory system, our results suggested that the speed of responses may rely on maturation of more pathways and cortical regions. In parallel, we studied face processing lateralization using a discrimination paradigm of faces presented in each hemifield and observed that only the right hemisphere was able to discriminate between faces. Further evidence also suggested a transfer of face-relevant information across hemispheres. To study speech processing lateralization, we used a paradigm with monaural presentation of speech stimuli. A comparison between typical infants and infants with callosal agenesis, suggested an asymmetric transfer of auditory information across hemispheres, facilitated toward the left hemisphere, that might contribute to the lateralization of language early on. This thesis highlights the potential of neuroimaging techniques for the study of brain’s structural and functional development and of hemispheric asymmetries early on.

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Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-10-13T15:08:09Z No. of bitstreams: 1 marceloluizdutravicente.pdf: 2312980 bytes, checksum: b37c60d826b1535e34d7681e6ff5daee (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-10-22T12:57:22Z (GMT) No. of bitstreams: 1 marceloluizdutravicente.pdf: 2312980 bytes, checksum: b37c60d826b1535e34d7681e6ff5daee (MD5) / Made available in DSpace on 2016-10-22T12:57:23Z (GMT). No. of bitstreams: 1 marceloluizdutravicente.pdf: 2312980 bytes, checksum: b37c60d826b1535e34d7681e6ff5daee (MD5) Previous issue date: 2008-03-07 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Estudos prévios têm mostrado que a agenesia calosa causada por irradiação ionizante prénatal promove alterações na expressão de lateralidade cerebral. Sugere-se que fatores genéticos possam estar envolvidos na expressão de lateralidade cerebral. A intenção deste trabalho foi estudar, em camundongos, as correlações entre expressões de lateralidade cerebral no teste de preferência de patas, que avaliou o comportamento lateralizado motor e no teste de campo aberto, que avaliou o comportamento lateralizado sensório-motor, quando avaliado o comportamento em sua periferia. No teste campo aberto, os animais foram divididos em subgrupos: aqueles que foram expostos a um fator sonoro contínuo estressante de 105 decibéis a 3000 Hz e os que não foram expostos. Foi testado um número total de 49 machos não irradiados e 51 fêmeas não irradiadas, 34 machos irradiados e 39 fêmeas irradiadas. Os instrumentos estatísticos utilizados foram análise de regressão com o coeficiente de Pearson e ANOVA. Os resultados mostraram índice de significância nas correlações lateralidade direcional da preferência de patas x lateralidade direcional do campo aberto e lateralidade direcional da preferência de patas x índice de lateralidade do campo aberto, em machos não irradiados sem som e em fêmeas não irradiadas com som. A modificação nos índices de lateralidade nos animais irradiados dos respectivos grupos sugere a participação da ontogênese calosa no estabelecimento da lateralidade como expressão conjunta. Além disto, a presença de índices de significância nos grupos não irradiados citados sugere a participação de fatores genéticos e/ou epigenéticos no estabelecimento da lateralidade como expressão conjunta. / Previous studies showed that callosal agenesis by exposition to prenatal ionizing irradiation leads to changes in the cerebral lateralized behavior. Other studies suggest genetic factors as involved in the establisment of cerebral lateralization. The intention this work was to study, in mice, the correlations between the establisment of the cerebral lateralization on the paw preference test, that objectives the study of motor laterality, and on the open-field test, that objetives the study of sensoriomotor lateralization on the periphery. In the open-field test the animals were subdivided in subgroups: that were exposed a stressing continuous sound factor of 105 dB and 3000 Hz and that weren’t exposed. It were tested 49 nonirradiated males, 51 nonirradiated females, 34 irradiated males, 39 irradiated females. The statistical tool used were the regression analysis with the Pearson Coefficient and the ANOVA. The results showed significance in correlations of directional laterality of the paw preference x directional laterality of the open-field, and in directional laterality of the paw preference x lateralisation index of the open-field. This was expressed in the nonirradiated males without sound and nonirradiated females with sound. The changes on the laterality index in the irradiated mice on the respective groups suggest the role of the callosal ontogenesis on the establisment of laterality as a dual expression. On the other hand, the presence of significance index on the above cited nonirradiated grouos suggest the role of genetic and/or epigenetic factors on the laterality establishment as a dual expression.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal