Activity-dependent myelination: A glial mechanism of oscillatory self-organization in large-scale brain networks

Noori, Rabiya; Park, Daniel; Griffiths, John; Bells, Sonya; Frankland, Paul W.; Mabbott, Donald; Lefebvre, Jérémie

doi:10.1073/pnas.1916646117

Cited by 99 publications

(86 citation statements)

References 61 publications

(113 reference statements)

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“…Given recent appreciation that activity-regulated myelination can influence neural network function (Pajevic et al, 2014;Noori et al, 2020;Steadman et al, 2020), we reasoned that excessive and aberrant neuronal activity might abnormally increase myelination within seizure networks in disorders such as absence epilepsy. Maladaptive myelination may, in turn, contribute to disease pathogenesis, including seizure kindling.…”

Section: Discussionmentioning

confidence: 99%

“…In general, epileptogenesis in absence and other forms of epilepsy is thought to reflect increased neuronal excitation and synchrony of neuronal firing (McCormick and Contreras, 2001;Jefferys et al, 2012;Pitkanen et al, 2015;Fogerson and Huguenard, 2016). Activityregulated myelination promotes oscillatory synchrony (Pajevic et al, 2014;Noori et al, 2020;Steadman et al, 2020); thus, aberrantly increased activity-regulated myelination may contribute to thalamocortical hypersynchrony underlying absence epilepsy. Consistent with our observations of increased callosal myelination, abnormally increased interhemispheric synchrony between the somatosensory cortices is well demonstrated in absence epilepsy (Mishra et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In the healthy brain, activity-dependent myelination functions to synchronize regions within distributed neuronal networks, and this process is required for multiple forms of learning (Gibson et al, 2014;McKenzie et al, 2014;Xiao et al, 2016;Geraghty et al, 2019;Noori et al, 2020;Pan et al, 2020;Steadman et al, 2020). We hypothesized that seizure-associated, abnormally increased myelination might contribute to thalamocortical network hypersynchrony during epileptogenesis (Makinson et al, 2017), increasing disease severity.…”

Section: Activity-dependent Myelination Contributes To Epileptogenesismentioning

confidence: 95%

“…While mechanisms of absence seizure kindling are incompletely understood, a common feature is excessive synchrony (coordinated firing of groups of neurons) in the thalamocortical network (Huntsman et al, 1999;Bai et al, 2011;Makinson et al, 2017;Tangwiriyasakul et al, 2018). Given the effect of activityregulated myelination on network synchrony (Noori et al, 2020;Steadman et al, 2020), we hypothesized that abnormally increased myelination induced by seizures might contribute to increasing seizure frequency during epileptogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Neuronal activity can modulate myelin development (Makinodan et al, 2012;Hines et al, 2015;Mensch et al, 2015) and promote new oligodendrocyte generation and myelination in cortical and callosal axons throughout life (Liu et al, 2012;Gibson et al, 2014;Hughes et al, 2018;Mitew et al, 2018;Swire et al, 2019;Steadman et al, 2020). Activity-regulated myelination is adaptive in the healthy brain, increasing neural network synchrony (Pajevic et al, 2014;Noori et al, 2020;Steadman et al, 2020) and contributing to cognitive functions including learning, attention and memory consolidation (McKenzie et al, 2014;Xiao et al, 2016;Geraghty et al, 2019;Steadman et al, 2020). The effects of myelin plasticity on network function in health raises the question of how activity-regulated myelination may modulate network function in disease states characterized by abnormal patterns of neuronal activity, such as epilepsy.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Maladaptive myelination promotes epileptogenesis in absence epilepsy

Knowles

Soane

Frost

et al. 2020

Preprint

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Neuronal activity can influence the generation of new oligodendrocytes (oligodendrogenesis) and myelination. In health, this is an adaptive process that can increase synchrony within distributed neuronal networks and contribute to cognitive function. We hypothesized that in seizure disorders, aberrant neuronal activity may promote maladaptive myelination that contributes to pathogenesis. Absence epilepsy is a disease defined by increasingly frequent behavioral arrest seizures over time, thought to be due to thalamocortical network hypersynchrony. We tested the hypothesis that activity-dependent myelination resulting from absence seizures promotes epileptogenesis. Using two distinct models of absence epilepsy, Wag/Rij rats and Scn8a+/mut mice, we found increased oligodendrogenesis and myelination specifically within the absence seizure network. These changes are evident only after seizure onset in both models and are prevented with pharmacological inhibition of seizures. Genetic blockade of activity-dependent myelination during epileptogenesis markedly decreased seizure frequency in the Scn8a+/mut mouse model of absence epilepsy. Taken together, these findings indicate that activity-dependent myelination driven by absence seizures contributes to seizure kindling during epileptogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Activity-dependent Myelination Contributes To Epileptogenesismentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Maladaptive myelination promotes epileptogenesis in absence epilepsy

Knowles

Soane

Frost

et al. 2020

Preprint

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Activity‐dependent alteration of early myelin ensheathment in a developing sensory circuit

Chorghay

MacFarquhar

et al. 2021

J of Comparative Neurology

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Myelination allows for the regulation of conduction velocity, affecting the precise timing of neuronal inputs important for the development and function of brain circuits. In turn, myelination may be altered by changes in experience, neuronal activity, and vesicular release, but the links between sensory experience, corresponding neuronal activity, and resulting alterations in myelination require further investigation. We thus studied the development of myelination in the Xenopus laevis tadpole, a classic model for studies of visual system development and function because it is translucent and visually responsive throughout the formation of its retinotectal system. We begin with a systematic characterization of the timecourse of early myelin ensheathment in the Xenopus retinotectal system using immunohistochemistry of myelin basic protein (MBP) along with third harmonic generation (THG) microscopy, a label-free structural imaging technique. Based on the mid-larval developmental progression of MBP expression in Xenopus, we identified an appropriate developmental window in which to assess the effects of early temporally patterned visual experience on myelin ensheathment. We used calcium imaging of axon terminals in vivo to characterize the responses of retinal ganglion cells over a range of stroboscopic stimulation frequencies. Strobe frequencies that reliably elicited robust versus dampened calcium responses were then presented to animals for 7 d, and differences in the amount of early myelin ensheathment at the optic chiasm were subsequently quantified. This study provides evidence that it is not just the presence but also to the specific temporal properties of sensory stimuli that are important for myelin plasticity.

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Transient demyelination causes long‐term cognitive impairment, myelin alteration and network synchrony defects

Mercier,

Quilichini,

Magalon

et al. 2024

Glia

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In the adult brain, activity‐dependent myelin plasticity is required for proper learning and memory consolidation. Myelin loss, alteration, or even subtle structural modifications can therefore compromise the network activity, leading to functional impairment. In multiple sclerosis, spontaneous myelin repair process is possible, but it is heterogeneous among patients, sometimes leading to functional recovery, often more visible at the motor level than at the cognitive level. In cuprizone‐treated mouse model, massive brain demyelination is followed by spontaneous and robust remyelination. However, reformed myelin, although functional, may not exhibit the same morphological characteristics as developmental myelin, which can have an impact on the activity of neural networks. In this context, we used the cuprizone‐treated mouse model to analyze the structural, functional, and cognitive long‐term effects of transient demyelination. Our results show that an episode of demyelination induces despite remyelination long‐term cognitive impairment, such as deficits in spatial working memory, social memory, cognitive flexibility, and hyperactivity. These deficits were associated with a reduction in myelin content in the medial prefrontal cortex (mPFC) and hippocampus (HPC), as well as structural myelin modifications, suggesting that the remyelination process may be imperfect in these structures. In vivo electrophysiological recordings showed that the demyelination episode altered the synchronization of HPC‐mPFC activity, which is crucial for memory processes. Altogether, our data indicate that the myelin repair process following transient demyelination does not allow the complete recovery of the initial myelin properties in cortical structures. These subtle modifications alter network features, leading to prolonged cognitive deficits in mice.

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Activity-dependent myelination: A glial mechanism of oscillatory self-organization in large-scale brain networks

Cited by 99 publications

References 61 publications

Maladaptive myelination promotes epileptogenesis in absence epilepsy

Maladaptive myelination promotes epileptogenesis in absence epilepsy

Activity‐dependent alteration of early myelin ensheathment in a developing sensory circuit

Transient demyelination causes long‐term cognitive impairment, myelin alteration and network synchrony defects

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