Mice running on wheels with irregularly spaced rungs will reveal how the brain’s insulation rewires itself during learning. The brain’s nerve cells are wrapped in a fatty sheath called myelin, which speeds up electrical signals. Until recently, scientists thought myelin was fixed once formed. But new evidence shows it can change with experience—a process called adaptive myelination. Exactly how this helps the brain learn remains unknown. This project aims to uncover the mechanism. The researchers will train mice to learn a motor skill—running on a wheel with uneven rungs—and track how myelin on active neurons shifts as the animals improve. They will then use genetic tools to block the pathways that might let myelin-making cells sense neural activity, and see whether learning still happens. They will also prevent new myelin from forming during training to test how it alters the connections between neurons. This is fundamental science. It will not produce a therapy or device tomorrow. But understanding how the brain rewires itself through myelin could eventually inform strategies to preserve cognitive function in ageing, or to improve recovery after stroke or spinal cord injury. Similar curiosity-driven work on neural plasticity has already reshaped rehabilitation medicine.
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In the vertebrate brain and spinal cord, cells called "oligodendrocytes" construct a fatty insulating layer around "axons" - long filamentous extensions of "neurons", the electrically excitable cells. This insulation, called "myelin", greatly speeds up the electrical signals sent by nerve cells as well as providing energetic support to neurons and their axons. Recently it has been demonstrated that oligodendrocytes and the myelin that they make also help the brain to adapt to new experiences, contributing to learning and memory formation. How exactly myelin influences learning is still not well understood. Our hypothesis is that oligodendrocytes can sense the neurons that are activated by specific behaviours, resulting in the formation or remodelling of myelin on those active neurons. We predict that this process will fine-tune electrical signals and alter the connectivity of the active neurons leading to the development of new neuronal circuits responsible for new behaviours. In this project we will train mice to learn a new motor skill (running on a wheel with irregularly spaced rungs) and observe how the myelin on activated neurons changes with learning. We will then use a number of different genetic manipulations to disrupt pathways that may enable oligodendrocytes to sense neuronal activity and determine if these mice maintain the ability to learn motor skills. We will also disrupt the formation and maintenance of new myelin that is formed during skill learning to ask how this process changes neuronal connectivity. Our experiments will help illuminate the general mechanisms underpinning one of the fundamental functions of the brain - the ability to adapt - and may provide insights into how better to maintain cognitive ability during healthy aging, or to aid recovery of brain function following disease or injury.
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