Critical function of Kir4.1 for the life-long generation of oligodendrocytes and myelin

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The massive computing power of the brain depends on the insulation of nerve cell connections with myelin sheaths, by cells known as oligodendrocytes. Bundles of these 'myelinated' connections form the white matter that is very prominent in the human cortex. The loss of myelin is a feature of multiple neuropathologies, most notably Multiple Sclerosis and other demyelinating diseases. However, myelin loss is also important in the poor clinical outcomes of cerebral palsy, stroke, and traumatic injury. Importantly, oligodendrocytes are continuously being lost and regenerated from a pool of stem cells in the brain, called oligodendrocyte progenitor cells (OPCs). These regenerative processes are essential for the life-long maintenance of myelin and for repair of myelin following damage. The failure or impairment of repair results in the loss of myelin and can have devastating effects on brain function. We have identified a key factor that is essential for oligodendrocyte generation, known as Kir4.1 channels. The aim of this project is to determine the importance of Kir4.1 in OPCs in the life-long generation of oligodendrocytes and myelin and maintenance of a healthy brain. This will provide new knowledge on the mechanisms controlling the generation of myelin and how this may go wrong in pathology and may ultimately lead to the identification of new cellular targets for protecting the healthy brain.