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Publication : Activity-Dependent Myelination of Parvalbumin Interneurons Mediated by Axonal Morphological Plasticity.

First Author  Stedehouder J Year  2018
Journal  J Neurosci Volume  38
Issue  15 Pages  3631-3642
PubMed ID  29507147 Mgi Jnum  J:261213
Mgi Id  MGI:6153638 Doi  10.1523/JNEUROSCI.0074-18.2018
Citation  Stedehouder J, et al. (2018) Activity-Dependent Myelination of Parvalbumin Interneurons Mediated by Axonal Morphological Plasticity. J Neurosci 38(15):3631-3642
abstractText  Axonal myelination of neocortical pyramidal neurons is modulated dynamically by neuronal activity. Recent studies have shown that a substantial proportion of neocortical myelin content is contributed by fast-spiking, parvalbumin (PV)-positive interneurons. However, it remains unknown whether the myelination of PV(+) interneurons is also modulated by intrinsic activity. Here, we used cell-type-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in adult mice to activate a sparse population of medial prefrontal cortex (mPFC) PV(+) interneurons. Using single-cell axonal reconstructions, we found that DREADD-stimulated PV(+) interneurons exhibited a nearly two-fold increase in total length of myelination, predominantly mediated by a parallel increase of axonal arborization and number of internodes. In contrast, the distribution of axonal interbranch segment distance and myelin internode length were not altered significantly. Topographical analysis revealed that myelination of DREADD-stimulated cells extended to higher axonal branch orders while retaining a similar interbranch distance threshold for myelination. Together, our results demonstrate that chemogenetically induced neuronal activity increases the myelination of neocortical PV(+) interneurons mediated at least in part by an elaboration of their axonal morphology.SIGNIFICANCE STATEMENT Myelination is the wrapping of an axon to optimize conduction velocity in an energy-efficient manner. Previous studies have shown that myelination of neocortical pyramidal neurons is experience and activity dependent. We now show that activity-dependent myelin plasticity in the adult neocortex extends to parvalbumin (PV)-expressing fast-spiking interneurons. Chemogenetic stimulation of PV interneurons in the medial prefrontal cortex (mPFC) significantly enhanced axonal myelination, which was paralleled by an increase in axonal arborization. This suggests that activity-dependent axonal plasticity may involve changes in both structural morphology and myelination. Such multicomponent plasticity reveals an unexpected repertoire of anatomical parameters available for optimizing and adapting neuronal networks in response to experience.
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