Individual Neuronal Subtypes Exhibit Diversity in CNS Myelination Mediated by Synaptic Vesicle Release

Abstract

SummaryRegulation of myelination by oligodendrocytes in the CNS has important consequences for higher-order nervous system function (e.g., [1, 2, 3, 4]), and there is growing consensus that neuronal activity regulates CNS myelination (e.g., [5, 6, 7, 8, 9]) through local axon-oligodendrocyte synaptic-vesicle-release-mediated signaling [10, 11, 12]. Recent analyses have indicated that myelination along axons of distinct neuronal subtypes can differ [13, 14], but it is not known whether regulation of myelination by activity is common to all neuronal subtypes or only some. This limits insight into how specific neurons regulate their own conduction. Here, we use a novel fluorescent fusion protein reporter to study myelination along the axons of distinct neuronal subtypes over time in zebrafish. We find that the axons of reticulospinal and commissural primary ascending (CoPA) neurons are among the first myelinated in the zebrafish CNS. To investigate how activity regulates myelination by different neuronal subtypes, we express tetanus toxin (TeNT) in individual reticulospinal or CoPA neurons to prevent synaptic vesicle release. We find that the axons of individual tetanus toxin expressing reticulospinal neurons have fewer myelin sheaths than controls and that their myelin sheaths are 50% shorter than controls. In stark contrast, myelination along tetanus-toxin-expressing CoPA neuron axons is entirely normal. These results indicate that while some neuronal subtypes modulate myelination by synaptic vesicle release to a striking degree in vivo, others do not. These data have implications for our understanding of how different neurons regulate myelination and thus their own function within specific neuronal circuits.

Myelination and mTOR

“…Following up on pioneering work (Barres & Raff, 1994; Demerens et al, 1996), electrical axonal activity and release of synaptic vesicles have been proposed recently as a major axonal signal modulating oligodendrogenesis, regulating the numbers and lengths of internodes generated, guiding the selection of axons to be myelinated, and adjusting the growth of myelin sheaths (Gibson et al, 2014; Hines, Ravanelli, Schwindt, Scott, & Appel, 2015; Koudelka et al, 2016; Mensch et al, 2015; Wake et al, 2015; Wake, Lee, & Fields, 2011). The molecular players underlying such activity‐dependent myelination are not univocally defined.…”

Oligodendroglia: metabolic supporters of neurons

“…Multiple studies have shown that myelin deposition is not static, but far more dynamic than initially thought, with adaptive changes in myelin driven by changes in neuronal activity (myelin plasticity) (6,(20)(21)(22)(23)(24)(25). These changes, e.g., induced by optogenetic stimulation or stimulated through learning of complex motor skills, promote oligodendrogenesis and the deposition of new myelin sheaths along the axons.…”

On Myelinated Axon Plasticity and Neuronal Circuit Formation and Function

“…Given that neuronal activity can regulate multiple stages of oligodendrocyte lineage 499 behaviour through myelination as well as axonal structure, it is likely that myelinated axon plasticity 500 plays a central role in many aspects of the formation and function of neuronal circuits that remain to 501 be discovered. activity-regulated myelination has been shown to be a property of only specific neuronal subtypes 514 (Koudelka et al, 2016). It will be important to define which neurons and circuits exhibit myelinatedaxon plasticity throughout life, and in response to experience.…”