Myelin Dynamics Throughout Life: An Ever-Changing Landscape?

Abstract

Myelin sheaths speed up impulse propagation along the axons of neurons without the need for increasing axon diameter. Subsequently, myelin (which is made by oligodendrocytes in the central nervous system) allows for highly complex yet compact circuitry. Cognitive processes such as learning require central nervous system plasticity throughout life, and much research has focused on the role of neuronal, in particular synaptic, plasticity as a means of altering circuit function. An increasing body of evidence suggests that myelin may also play a role in circuit plasticity and that myelin may be an adaptable structure which could be altered to regulate experience and learning. However, the precise dynamics of myelination throughout life remain unclear - does the production of new myelin require the differentiation of new oligodendrocytes, and/or can existing myelin be remodelled dynamically over time? Here we review recent evidence for both de novo myelination and myelin remodelling from pioneering longitudinal studies of myelin dynamics in vivo, and discuss what remains to be done in order to fully understand how dynamic regulation of myelin affects lifelong circuit function.

Keywords: adaptive myelination; circuit plasticity; myelin; myelin remodelling; oligodendrocyte.

FIGURE 1

Oligodendrocyte and myelin dynamics in the mammalian cortex throughout life. (A) Oligodendrocyte precursor cells (OPCs) continuously generate new myelinating oligodendrocytes (OLs) in the somatosensory cortex from birth up to middle age. The OL population then declines in old age, accompanied by a reduction in myelin coverage. (B) Lineage-tracing of single OPCs shows that although premyelinating OLs are continuously produced in adulthood, only approximately 20% survive to myelinate. Most myelin sheaths, once formed, are stable in length over prolonged period of time, indicating that there is normally very little remodelling of existing myelin. Summary of data from Hill et al. (2018) and Hughes et al. (2018).

FIGURE 2

Myelin remodelling can occur in vivo. (A) Ablation of single sheaths on a fully myelinated axon can induce the rapid growth of neighbouring sheaths to cover the gap. This gap can either be covered entirely by the neighbouring sheaths, or the original myelination profile can be restored by the addition of a new sheath. (B) Ablation of a sheath on a sparsely myelinated axon is followed by formation of a new myelin sheath of identical size and location to the ablated predecessor sheath. Summary of data from Auer et al. (2018).