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The role of oligodendrocytes in higher-order circuit functions

dc.contributor.advisorNave, Klaus-Armin Prof. Dr.
dc.contributor.authorMoore Corona, Sharlen Yared
dc.titleThe role of oligodendrocytes in higher-order circuit functionsde
dc.contributor.refereeSimons, Mikael Prof. Dr.
dc.description.abstractengThe historical conception of glial cells as the ‘glue’ that holds the brain together has dramatically changed in the last years. The glia plays an active role in several mechanisms related to information processing in the brain and thus can change and shape circuits during development, adulthood and in an experience-dependent manner. Due to the recently described novel characteristics and roles that these cells have in brain function, we currently face ourselves with the necessity of widening the ‘neuro’ in neurosciences and give them the appropriate place they deserve. Focusing on oligodendroglia, the better-known function of these cells is to wrap axons in the central nervous system to facilitate propagation of action potentials along axons. There is also evidence for a role in metabolic support of the axons they wrap that is partially independent of myelination per se. Furthermore, nowadays we know this wrapping process is extraordinarily complex and prone to plastic modifications for the adaptation of information transmission, and vulnerable to injury. The study of sensory and cognitive abnormalities in patients with myelin lesions has provided evidence to understand the function of myelin in information processing. Nevertheless, due to the substantial heterogeneity of these myelin lesions within the study populations, the correlation of specific dysfunctions with an observed phenotype results in a difficult task. Additionally, the complexity of the contact, communication, and maintenance between axons and oligodendrocytes makes it difficult to dissect the partially independent roles that these cells have in information processing. Studies for the dynamic in vivo assessment of combined neuronal and oligodendrocyte functions are very scarce in the field and have only very recently begun to emerge. In this study, I assessed axonal auditory cortical function in mutant mice with either dysmyelination phenotypes or reduced metabolic axo-glial support to the axons. I found that dysmyelination generated deficits in temporal sound processing known to be essential for speech understanding. The perceptual deficits correlated with defects seen in the spiking activity of cortical cells. Together, they could not be explained by a loss in conduction velocity alone, suggesting that mechanisms that are secondary to the loss of myelin per se, are accounting for the diverse effects observed. Indeed, mice with oligodendrocyte-specific deficits in metabolic processes but relatively minor deficits in myelination showed similar impairments to those found with dysmyelination. A parallel study of the role of myelin in task-specific brain lateralization revealed that myelin helps the establishment, but not the maintenance of this circuit function. Overall my study shows, for the first time, that oligodendrocytes play crucial roles in normal circuit function in high order processing and this role goes beyond to the regulation of conduction velocity. The observations made in this study highlight the importance of glial cells in normal brain function and disease, and emphasize in particular the importance of the cooperative research of neuro-glial
dc.contributor.coRefereeHülsmann, Swen Prof. Dr.
dc.contributor.thirdRefereeMoser, Tobias Prof. Dr.
dc.contributor.thirdRefereeHeinrich, Ralf Prof. Dr.
dc.contributor.thirdRefereeDean, Camin Dr.
dc.contributor.thirdRefereeHoz, Livia de Dr.
dc.subject.engAuditory systemde
dc.subject.engCortical processingde
dc.subject.engTemporal acuityde
dc.subject.engMetabolic supportde
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de

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