Local axonal morphology guides the topography of interneuron myelination in mouse and human neocortex
- Erasmus University Medical Center, Netherlands
- Brown University, United States
Abstract
GABAergic fast-spiking parvalbumin-positive (PV) interneurons are frequently myelinated in the cerebral cortex. However, the factors governing the topography of cortical interneuron myelination remain incompletely understood. Here, we report that segmental myelination along neocortical interneuron axons is strongly predicted by the joint combination of interbranch distance and local axon caliber. Enlargement of PV+ interneurons increased axonal myelination, while reduced cell size led to decreased myelination. Next, we considered regular-spiking SOM+ cells, which normally have relatively shorter interbranch distances and thinner axon diameters than PV+ cells, and are rarely myelinated. Consistent with the importance of axonal morphology for guiding interneuron myelination, enlargement of SOM+ cell size dramatically increased the frequency of myelinated axonal segments. Lastly, we confirm that these findings also extend to human neocortex by quantifying interneuron axonal myelination from ex vivo surgical tissue. Together, these findings establish a predictive model of neocortical GABAergic interneuron myelination determined by local axonal morphology.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-9. Fiji ImageJ code for semi-automated reconstruction of axon diameter has been provided as an additional file. Human and mouse PV cell reconstructions will be uploaded to NeuroMorpho (http://neuromorpho.org/).
Article and author information
Author details
Funding
Horizon 2020 Framework Programme (NEURON-JTC2018-024)
- Steven A Kushner
ZonMw (40-00812-98-15030)
- Steven A Kushner
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (834.12.002)
- Steven A Kushner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sacha B Nelson, Brandeis University, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (IG 15-064) of the Dutch Ethical Committee (DEC). The protocol was approved by the Netherlands Centrale Commissie Dierproeven (Permit Number: AVD1010020173544). All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.
Human subjects: All procedures regarding human tissue were performed with the approval of the Medical Ethical Committee of the Erasmus University Medical Center. Written informed consent of each patient was provided in accordance with the Helsinki Declaration.
Version history
- Received: May 20, 2019
- Accepted: November 18, 2019
- Accepted Manuscript published: November 19, 2019 (version 1)
- Version of Record published: December 23, 2019 (version 2)
Copyright
© 2019, Stedehouder et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Local axonal morphology guides the topography of interneuron myelination in mouse and human neocortex
eLife 8:e48615.
https://doi.org/10.7554/eLife.48615
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