Developmental myelination and myelin plasticity during spatial working memory task acquisition
Myelin is essential for brain functioning, as it enables fast signal propagation and synchronisation of neuronal impulses. Myelin sheaths are created by oligodendrocytes, which stem from oligodendrocyte precursor cells. During development neurons become myelinated, and this process can be modulated by environmental factors, ageing and various neurological disorders. The notion that myelin plays a role in learning has increasingly received attention within the scientific community, and it is speculated that cognition and learning are likely influenced and regulated by glial cells. In this thesis, I focussed on three areas in order to gain a better understanding of myelin development and plasticity: methods to image myelin, the development of myelin and its microstructure over the course of a lifespan, and the question whether learning a new task will lead to new myelin formation in the brain regions upon which the task is dependent. To image myelin, I have applied several techniques, ranging from methods to make the tissue transparent and therefore aid myelin visualisation (RapiClear, Expansion Microscopy), to two-photon 3D whole brain imaging (TissueVision) and Magnetic Resonance Imaging (MRI). In order to visualise and quantify myelination patterns and myelin internodes during development, I applied immunohistochemistry and high resolution confocal microscopy. Finally, for establishing whether cognitive learning affects oligodendrocyte differentiation, I employed a touchscreen-based spatial working memory task. A task that is similar to cognitive paradigms used for humans, allowing for potential translation to human cognitive functioning. In summary, I find that myelin develops in a specific pattern over time in the mouse cortex, slowly progressing upward up from the deeper cortical layers to the surface of the brain. Furthermore, over the course of a lifespan myelin internodes lengths become more variable. This increased variability could potentially represent myelin plasticity across their lifespan. Finally, I find that there is an increase in differentiating myelinating oligodendrocytes in animals that learn a spatial working memory task, compared to animals that do not (in the areas that are required for learning and performing this task), supporting the notion of myelin plasticity.