Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity

Abstract

Myelin controls the time required for an action potential to travel from the neuronal soma to the axon terminal, defining the temporal manner in which information is processed within the CNS. The presence of myelin, the internodal length, and the thickness of the myelin sheath are powerful structural factors that control the velocity and fidelity of action potential transmission. Emerging evidence indicates that myelination is sensitive to environmental experience and neuronal activity. Activity-dependent modulation of myelination can dynamically alter action potential conduction properties but direct functional in vivo evidence and characterization of the underlying myelin changes is lacking. We demonstrate that in mice long-term monocular deprivation increases oligodendrogenesis in the retinogeniculate pathway but shortens myelin internode lengths without affecting other structural properties of myelinated fibers. We also demonstrate that genetically attenuating synaptic glutamate neurotransmission from retinal ganglion cells phenocopies the changes observed after monocular deprivation, suggesting that glutamate may constitute a signal for myelin length regulation. Importantly, we demonstrate that visual deprivation and shortened internodes are associated with a significant reduction in nerve conduction velocity in the optic nerve. Our results reveal the importance of sensory input in the building of myelinated fibers and suggest that this activitydependent alteration of myelination is important for modifying the conductive properties of brain circuits in response to environmental experience.

Ephrin‐A1‐EphA4 signaling negatively regulates myelination in the central nervous system

“…This is similar to what has been observed previously after knockdown of Nogo , or activation of Fyn (Czopka et al, 2013), suggesting that different signals are regulating initial myelin sheath formation and elongation. The specific molecules involved in regulating sheath length are currently unknown, but the involvement of neuronal activity has been demonstrated (Etxeberria et al, 2016;Hines et al, 2015;Koudelka et al, 2016). Such an interpretation is in line with recent experiments in zebrafish where shorter sheaths were found to be more likely to retract (Hines et al, 2015).…”

Architecting the myelin landscape

“…Notably, other studies have found no [47] or opposite [48] effects of neuronal activity on OPC differentiation, while others have observed differences in properties such as OL internode number [47,49••], length [48,50••,51•], or thickness [42,46,47,52]. Of these, two pioneering studies found a direct role for the synaptic activity of individual axons in regulating their selection for myelination.…”

Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival

“…Conversely, blocking glutamate uptake into secretory vesicles in retinal ganglion cells in early postnatal mice increased the number of OLs that developed in the optic tract, suggesting that glutamate signalling negatively regulates OL development (Etxeberria et al, 2016). Glutamate-evoked NMDA receptor (NMDAR)-mediated signalling in OL lineage cells has been suggested to accelerate the myelination of active axons (Lundgaard et al, 2013), which might occur by NMDAR activation up-regulating glucose transport into developing OLs (Saab et al, 2016).…”