Adaptive myelination in learning and memory

We found that production of new oligodendrocytes (OLs) is stimulated by, and required for, motor skill learning in mice. New OL production was required within 2-3 hours of mice engaging with the motor task, seemingly too soon for full myelin wrapping. We will therefore investigate how, at the cellular level, OLs contribute to early-stage learning, by interfering genetically with pre-myelinating functions of OLs including process outgrowth and ensheathment, or metabolic coupling between OLs and axons. We will also investigate signalling between axons and OLs to ask whether AMPA receptor-mediated synaptic input to OLs selects electrically active axons for myelination over their inactive or less-active neighbours, and whether this contributes to learning. Recently, we found that active OL generation is required for non-motor, "cognitive" learning in a T-maze test, which relies on short-term working memory and longer-term reference memory in a spatial context. We will use additional maze tests to dissociate working and reference memory and test the hypothesis that adult OL genesis is a general requirement for goal-directed learning and memory processes. We will also perform a genetic test of the idea that myelinating OLs, which are extremely long-lived, are required for preserving long-term memories.