Figure 4 |. Non-synaptic junctions on myelinating glia promote preferential myelination of electrically active axons.

a | Oligodendrocyte progenitor cells (OPCs) were co-cultured with a mixture of mouse dorsal root ganglion neurons in which vesicle release from axons was blocked by botulinum toxin (BnTX; red axons) or was not blocked (yellow axons). The experiments show that myelination by oligodendrocytes is preferentially induced on electrically active axons releasing vesicles. b | Specialized contacts form between axons and oligodendrocyte cell processes, which lack the morphological and electrophysiological features of synapses but signal via release of neurotransmitters (glutamate and ATP) from axons. Neurotransmitters released at non-synaptic axo-glial junctions signal electrical activity in axons to oligodendrocytes and cause an increase in intracellular Ca²⁺ in the glial cell. c | Electrical stimulation of axons causes release of glutamate from vesicles that activate NMDA receptor (NMDAR) and metabotropic glutamate receptor (mGluR) on oligodendrocyte cell processes. This in turn triggers formation of the axoglial signalling complex (involving the SRC family kinase FYN, cell adhesion molecules (CAMs) L1CAM) and F3 (also known as contactin), laminin and integrin) and phosphorylation of FYN. Activated FYN phosphorylates heterogeneous nuclear ribonucleoprotein A2, resulting in local myelin basic protein (MBP) translation from mRNA in oligodendrocyte cell processes. The graph in the right-hand panel demonstrates that formation of the axo-glial signalling complex and local synthesis of MBP are inhibited by axonal firing when NMDAR and mGluR activation are blocked by BnTX. d | Three weeks after stimulating action potentials in axons, the number and length of myelin segments formed on axons releasing synaptic vesicles (yellow axons in diagram on the left and blue bars in graphs on the right) was much higher than on axons in which vesicle release was not blocked by BnTX. AAAAAA, poly(A) tail of mRNA. Parts b–d are from REF. 80, Nature Publishing Group. Part c is also from Wake, H., Lee, P. R. & Fields, R. D. Control of local protein synthesis and initial events in myelination by action potentials. Science 333, 1647–1651 (2011). Reprinted with permission from AAAS.