Axonal activity-dependent myelination in development: Insights for myelin repair

• Current research is focused on understanding the cues that drive remyelination.
• Studies show that neuronal activity positively regulates developmental myelination.
• Accumulating data suggest that electrical activity could also promote remyelination.
• Axon-glia signaling could involve synapse-like connections and/or paracrine factors.
• Distinct responses of OPCs and NPCs to activity could influence myelin repair.

Recent advances in transgenic tools have allowed us to peek into the earliest stages of vertebrate development to study axon-glial communication in the control of peri-natal myelination. The emerging role of neuronal activity in regulating oligodendrocyte progenitor cell behavior during developmental myelination has opened up an exciting possibility—a role for neuronal activity in the early stages of remyelination. Recent work from our laboratory and others has also shown that contrary to previously established dogma in the field, complete remyelination up to pre-demyelination levels can be achieved in mouse models of MS by oligodendrogenic neural precursor cells that derive from the adult subventricular zone. These cells are electrically active and can be depolarized, suggesting that neuronal activity may have a modulatory role in their development and remyelination potential. In this review, we summarize recent advances in our understanding of the development of axon-glia communication and apply those same concepts to remyelination, with an emphasis on the particular roles of different sources of oligodendrocyte progenitor cells.