Neuron-class specific responses govern adaptive remodeling of myelination in the neocortex

Abstract

Myelination plasticity plays a critical role in neurological function, including learning and memory. However, it is unknown whether this plasticity is enacted through 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 to investigate the dynamics of myelin sheaths along single axons of both excitatory callosal projection neurons and inhibitory parvalbumin+ interneurons in layer 2/3 of adult mouse visual cortex. We find that both neuron types show dynamic, homeostatic myelin remodeling under normal vision. However, monocular deprivation results in experience-dependent adaptive myelin remodeling only in parvalbumin+ interneurons, but not in callosal projection neurons. Monocular deprivation induces an initial increase in elongation events in myelin segments of parvalbumin+ interneurons, followed by a contraction phase affecting a separate cohort of segments. Sensory experience does not alter the generation rate of new myelinating oligodendrocytes, but can recruit pre-existing oligodendrocytes to generate new myelin sheaths. Parvalbumin+ interneurons also show a concomitant increase in axonal branch tip dynamics independent from myelination events. These findings suggest that adaptive myelination is part of a coordinated suite of circuit reconfiguration processes, and demonstrate that distinct classes of neocortical neurons individualize adaptive remodeling of their myelination profiles to diversify circuit tuning in response to sensory experience.

Nerve Growth Factor Neutralization Promotes Oligodendrogenesis by Increasing miR-219a-5p Levels

“…The finding that NGF modulates myelination via miR-219 hints at a potential involvement of NGF in myelin plasticity. Myelination in the CNS is dynamically modulated by neuronal activity, even in a neuron-specific fashion [54], and it contributes to brain plasticity, learning, and memory [55]. Consistently, mir-219 is strongly upregulated in the visual cortex at the peak of the critical period, with respect to its onset [56].…”

Myelin biogenesis is associated with pathological ultrastructure that is resolved by microglia during development

“…We also wondered whether myelin ingestion by microglia could be attributed to myelin sheath retractions (Auer, Vagionitis, & Czopka, 2018; Czopka, ffrench-Constant, & Lyons, 2013; Hines, Ravanelli, Schwindt, Scott, & Appel, 2015; Liu, Du, & He, 2013; Orthmann-Murphy et al, 2020; Yang, Michel, Jokhi, Nedivi, & Arlotta, 2020), a common form of myelin plasticity. We therefore analyzed retractions in 3-4 dpf Tg(mpeg1:EGFP; mbp:mCherry-CAAX) dorsal spinal cords in time-lapses of 30 minute intervals over 10-14 hours.…”

Neuron–Oligodendrocyte Communication in Myelination of Cortical GABAergic Cells

“…Differences between myelin of GABAergic and pyramidal cells also extend to remodeling during adaptive responses. Myelinated axons of callosal excitatory projection neurons and PV + interneurons from cortical layer II/III were compared in an in vivo two-photon imaging study of PLP-eGFP mice [ 179 ]. During adaptive changes induced by monocular deprivation, myelin of PV + interneurons showed balanced elongations and contractions while myelin of excitatory neurons tended to display elongations alone [ 179 ].…”

“…Adaptive myelination of PV + cells, which innervate large numbers of pyramidal cells, may enhance rhythmic population activities. During the adaptive remodeling of PV + cells, myelination profiles are specific to each cell [ 179 ].…”