Abstract
Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.
Highlights
Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry
We utilized the hM3Dq DREADD, which causes depolarization of neurons in response to the synthetic ligand clozapineN-oxide (CNO) or its metabolite clozapine[20, 21]
We confirmed that CNO directly mediates depolarization and action potential firing in hM3Dq-expressing neurons by performing whole-cell patch clamp recordings of transduced pyramidal neurons in cortical slices (Supplementary Fig. 2)
Summary
Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. Recent evidence from rodent studies suggest that white matter structural changes, potentially associated with increased myelination, are directly proportional to the level of performance in a motor task[10] and indicate that motor learning requires the addition of newly generated oligodendrocytes[11]. A variety of model systems provide evidence for both possibilities Both in vitro and in vivo studies have demonstrated that increasing neuronal activity positively regulates OPC proliferation[12,13,14] resulting in increased production of oligodendrocytes and myelin[12]. Other studies have shown that blocking neuronal activity has the opposite effect, decreasing OPC proliferation[15, 16] In addition to these paracrine effects on local OPC proliferation, recent evidence indicates that neuronal activity directly influences axonal selection for myelination such that differentiating oligodendrocytes preferentially myelinate electrically active axons.
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