Preservation of a remote fear memory requires new myelin formation

Pan, Simon; Mayoral, Sonia R.; Choi, Hye Sun; Chan, Jonah R.; Kheirbek, Mazen A.

doi:10.1038/s41593-019-0582-1

Cited by 264 publications

(328 citation statements)

References 52 publications

(53 reference statements)

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“…In addition, converging evidence suggests that myelin can be dynamically modulated by neuronal activity and contributes to nervous system plasticity throughout life [8][9][10][11] . Myelin plasticity in response to experience helps to shape brain structure and function, including learning and memory 5,[12][13][14] . Previous studies of experiencedependent myelin plasticity have demonstrated the importance of myelination by newly-formed oligodendrocytes 7,8,[10][11][12][13][14] , but the neuronal substrates and dynamic properties of adaptivelyremodeled myelin segments have not yet been addressed.…”

Section: Main Textmentioning

confidence: 99%

“…Myelin plasticity in response to experience helps to shape brain structure and function, including learning and memory 5,[12][13][14] . Previous studies of experiencedependent myelin plasticity have demonstrated the importance of myelination by newly-formed oligodendrocytes 7,8,[10][11][12][13][14] , but the neuronal substrates and dynamic properties of adaptivelyremodeled myelin segments have not yet been addressed. It has been shown that different neuron subtypes have distinct patterns of axonal myelination, and, furthermore, that myelin profiles vary between individual cells within neuronal classes [15][16][17] .…”

Section: Main Textmentioning

confidence: 99%

“…The cortex continues to add new myelin sheaths throughout life 6,7,14 . To test whether new myelin segments have distinct dynamic characteristics compared to pre-existing internodes, we We next examined the level of remodeling of new sheaths compared to pre-existing sheaths, by comparing the imaging session in which individual new sheaths were first identified with sessions one and two weeks later ( Figure 2G).…”

Section: De Novo Generated Myelin Sheaths Are More Dynamicmentioning

confidence: 99%

“…In the cases where axonal branch remodeling co-occurred with myelin plasticity in PV-INs, most of the combined axon and myelin remodeling events were observed when new sheaths were produced, although it remains possible that shorter contractions or elongations of myelin segments may have been excluded from the analysis due to higher uncertainty in their measurements (see Prior reports have shown that neuronal activity and experience modulate myelination 8,9,25,31,32 , and that active myelination by newly-formed oligodendrocytes is necessary for learning and memory [12][13][14] . The results presented here suggests a novel framework for conceptualizing activity-and experience-dependent myelin plasticity, where cell type-specific adaptive remodeling of myelination allows different neurons to modify their individual functions and potentiates the tuning capacity of neuronal networks.…”

Section: Md-induced Remodeling Of Pv + Interneuron Axons Is Independementioning

confidence: 99%

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

Yang

Michel

Jokhi

et al. 2020

Preprint

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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.

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Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: De Novo Generated Myelin Sheaths Are More Dynamicmentioning

confidence: 99%

Section: Md-induced Remodeling Of Pv + Interneuron Axons Is Independementioning

confidence: 99%

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

Yang

Michel

Jokhi

et al. 2020

Preprint

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“…In vivo, myelin can be specifically targeted to individual axons in a complex milieu (5), and can be highly regulated throughout life (6). Indeed, dynamic changes to myelin sheaths have been proposed to adapt circuit function to novel experiences, including learning (7,8), social interactions (9)(10)(11), as well as memory formation and recall (12)(13)(14). Neuronal activity is now known to regulate oligodendrocyte lineage progression (15).…”

Section: Mainmentioning

confidence: 99%

Synaptic vesicle fusion along axons is driven by myelination and subsequently accelerates sheath growth in an activity-regulated manner

Almeida

Williamson

Madden

et al. 2020

Preprint

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To study activity-regulated myelination, we imaged synaptic vesicle fusion along single axons in living zebrafish, and found, surprisingly, that axonal synaptic vesicle fusion is driven by myelination. This myelin-induced axonal vesicle fusion was enriched along the unmyelinated domains into which newly-formed sheaths grew, and was promoted by neuronal activity, which in turn accelerated sheath growth. Our results indicate that neuronal activity consolidates sheath growth along axons already selected for myelination.

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Developing Hypoimmunogenic Human iPSC‐Derived Oligodendrocyte Progenitor Cells as an Off‐The‐Shelf Cell Therapy for Myelin Disorders

Feng,

Chao,

et al. 2023

Advanced Science

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Demyelinating disorders are among the most common and debilitating diseases in neurology. Canavan disease (CD) is a lethal demyelinating disease caused by mutation of the aspartoacylase (ASPA) gene, which leads to the accumulation of its substrate N‐acetyl‐l‐aspartate (NAA), and consequently demyelination and vacuolation in the brain. In this study, hypoimmunogenic human induced pluripotent stem cell (iPSC)‐derived oligodendrocyte progenitor cells (OPC) are developed from a healthy donor as an “off‐the‐shelf” cell therapy. Hypoimmunogenic iPSCs are generated through CRISPR/Cas9 editing of the human leukocyte antigen (HLA) molecules in healthy donor‐derived iPSCs and differentiated into OPCs. The OPCs are engrafted into the brains of CD (nur7) mice and exhibit widespread distribution in the brain. The engrafted OPCs mature into oligodendrocytes that express the endogenous wildtype ASPA gene. Consequently, the transplanted mice exhibit elevated human ASPA expression and enzymatic activity and reduced NAA level in the brain. The transplanted OPCs are able to rescue major pathological features of CD, including defective myelination, extensive vacuolation, and motor function deficits. Moreover, the hypoimmunogenic OPCs exhibit low immunogenicity both in vitro and in vivo. The hypoimmunogenic OPCs can be used as “off‐the‐shelf” universal donor cells to treat various CD patients and many other demyelinating disorders, especially autoimmune demyelinating diseases, such as multiple sclerosis.

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Preservation of a remote fear memory requires new myelin formation

Cited by 264 publications

References 52 publications

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

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

Synaptic vesicle fusion along axons is driven by myelination and subsequently accelerates sheath growth in an activity-regulated manner

Developing Hypoimmunogenic Human iPSC‐Derived Oligodendrocyte Progenitor Cells as an Off‐The‐Shelf Cell Therapy for Myelin Disorders

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