Research Article

Neuron class–specific responses govern adaptive myelin remodeling in the neocortex

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Science  18 Dec 2020:
Vol. 370, Issue 6523, eabd2109
DOI: 10.1126/science.abd2109

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Cellular effects of visual deprivation

Myelination speeds the progress of action potentials along neuronal axons. Yang et al. studied changes in myelination in the mouse visual cortex in response to visual experience (see the Perspective by Yalçin and Monje). With normal vision, myelination is continuously remodeled. As ocular dominance shifts in response to monocular deprivation, myelination patterns change on certain inhibitory interneurons but not on excitatory callosal projection neurons. Myelin sheaths are both added and subtracted, segments of myelin elongate and contract, and preexisting oligodendrocytes make new myelin sheaths. This adaptive myelination helps to diversify neuronal function and remodel neuronal circuits in response to sensory experience.

Science, this issue p. eabd2109; see also p. 1414

Structured Abstract


Myelin is a fundamental structure in the vertebrate nervous system, and its precise formation and regulation are critical for complex neuronal function, including learning and memory. Even small modifications in myelin sheath structure can substantially affect neural network performance. It has been shown that neuronal activity and experience modulate myelination; however, it is unknown whether this plasticity reflects uniform changes across all neuronal subtypes, or whether adaptive myelin remodeling has cell type–specific characteristics that may potentiate circuit tuning, either under normal conditions or driven by experience.


We investigated experience-dependent remodeling of myelination profiles on different classes of neurons using longitudinal, dual-color in vivo two-photon imaging in the adult neocortex, both during normal vision and through a period of ocular dominance plasticity induced through monocular deprivation (MD). MD is a classical model used to study sensory experience–dependent plasticity, which is known to drive adaptive changes in layer 2/3 (L2/3) γ-aminobutyric acid–releasing (GABAergic) and pyramidal neurons, at both the physiological and the structural level. It has been reported that >90% of the myelin in L2/3 of the neocortex wraps around axons of either excitatory neurons or parvalbumin-expressing GABAergic interneurons (PV-INs). We therefore used MD to interrogate whether sensory experience might drive differential adaptive remodeling of myelin profiles on excitatory callosal projection neurons (CPNs) versus inhibitory PV-INs.


Using genetic identification of cell types, we imaged myelinating oligodendrocytes simultaneously with L2/3 PV-INs or CPNs within the binocular area of primary visual cortex in young adult mice. During normal homeostatic conditions, we found that both excitatory CPNs and inhibitory PV-INs display remodeling of preexisting myelin sheaths as well as de novo generation of myelin segments. Preexisting myelin sheaths present neuronal cell type–specific patterns of plasticity under normal vision, with L2/3 PV-INs displaying a balanced ratio of elongations and contractions, whereas CPNs exhibit shorter myelin sheaths and an overall elongation of segments over time. However, MD elicits an increase in myelin sheath dynamics specifically in PV-INs, whereas CPN myelination remains unchanged from baseline plasticity. This experience-dependent remodeling takes the form of an initial phase of segment elongations followed by a contraction phase that affects a separate cohort of myelin segments. In addition, the adaptive changes in the longitudinal patterns of PV-IN myelination induced by MD are associated with an increase in the displacement rate of putative nodes of Ranvier. Sensory experience does not alter the integration rate of new myelinating oligodendrocytes but can recruit preexisting oligodendrocytes to generate new myelin segments. These changes in PV-INs are accompanied by a concomitant increase in axonal branch tip dynamics during MD that is independent from myelination events.


Our findings unearth previously unappreciated dynamics of myelin plasticity that are neuron type–specific. We show that even when distinct neuronal subpopulations are interconnected within the same circuit, surrounded by a shared environment, and myelinated by a common set of oligodendrocytes, they display class-specific patterns of myelin changes. The data suggest that adaptive myelination is part of a coordinated suite of circuit reconfiguration processes that are cell type–specific and put forward a conceptual framework in which distinct classes of neocortical neurons individualize adaptive remodeling of their myelination profiles to diversify circuit tuning in response to sensory experience.

Myelin plasticity is neuron class–specific.

In vivo two-photon imaging is used to show that in normal conditions, L2/3 PV-INs display a balanced remodeling of preexisting myelin sheaths, whereas CPNs present a bias for elongation. MD induces an initial increase in elongating myelin sheaths followed by a phase of contraction in PV-INs, whereas myelin dynamics in CPN remains unaffected by this alteration in sensory experience.


Myelin plasticity is critical for neurological function, including learning and memory. However, it is unknown whether this plasticity reflects uniform changes across all neuronal subtypes, or whether myelin dynamics vary between neuronal classes to enable fine-tuning of adaptive circuit responses. We performed in vivo two-photon imaging of myelin sheaths along single axons of excitatory callosal neurons and inhibitory parvalbumin-expressing interneurons in adult mouse visual cortex. We found that both neuron types show homeostatic myelin remodeling under normal vision. However, monocular deprivation results in adaptive myelin remodeling only in parvalbumin-expressing interneurons. An initial increase in elongation of myelin segments is followed by contraction of a separate cohort of segments. This data indicates that distinct classes of neurons individualize remodeling of their myelination profiles to diversify circuit tuning in response to sensory experience.

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