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Axoglial synapses, adult myelination and motor skills learning

Final Report Summary - MOTOGLIA (Axoglial synapses, adult myelination and motor skills learning)

We showed (Young et al., 2013) that oligodendrocytes precursors (OPs) continue to proliferate and differentiate into myelinating oligodendrocytes throughout young adult life in mice, raising questions about the function of the late-born cells. We also showed that lateborn oligodendrocytes in the optic nerve have a distinctive morphology with many more, shorter myelin sheaths than those born in the early postnatal period, suggesting that myelin is continuously remodelled during adult life. This has helped fuel an explosion of interest in myelin plasticity in response to life experience and/or the environment. We contributed to this exciting new field by showing that oligodendrocyte development is accelerated and required during motor skill learning in mice - the first demonstration of a causal link between adult gliogenesis, learning and memory. That article became a "hot paper" - i.e. in the top 0.1% of papers in its field, based on the number of citations one year post-publication (source: Web of Science) (McKenzie et al., 2014). We showed subsequently that new oligodendrocyte production is initiated and required very early - within the first few hours of the start of motor training (Xiao et al., 2016). This indicates that myelination is an integral part of skills learning, required hand-in-hand with (or close on the heels of) synaptic strengthening, the "classical" mechanism of Hebbian learning. Most recently we have shown that synaptic communication between electrically active axons and oligodendrocyte lineage cells, mediated via AMPA-type glutamate receptors on OPs and pre-myelinating oligodendrocytes, promotes myelination by enhancing oligodendrocyte survival (Kougioumtzidou et al., 2017).