1. Neuroscience
Download icon

A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons

  1. Kristina D Micheva  Is a corresponding author
  2. Dylan Wolman
  3. Brett D Mensh
  4. Elizabeth Pax
  5. JoAnn Buchanan
  6. Stephen J Smith
  7. Davi D Bock  Is a corresponding author
  1. Stanford University, United States
  2. Janelia Research Campus, Howard Hughes Medical Institute, United States
  3. Allen Institute for Brain Science, United States
Research Article
  • Cited 115
  • Views 5,040
  • Annotations
Cite this article as: eLife 2016;5:e15784 doi: 10.7554/eLife.15784

Abstract

Myelin is best known for its role in increasing the conduction velocity and metabolic efficiency of long-range excitatory axons. Accordingly, the myelin observed in neocortical gray matter is thought to mostly ensheath excitatory axons connecting to subcortical regions and distant cortical areas. Using independent analyses of light and electron microscopy data from mouse neocortex, we show that a surprisingly large fraction of cortical myelin (half the myelin in layer 2/3 and a quarter in layer 4) ensheathes axons of inhibitory neurons, specifically of parvalbumin-positive basket cells. This myelin differs significantly from that of excitatory axons in distribution and protein composition. Myelin on inhibitory axons is unlikely to meaningfully hasten the arrival of spikes at their pre-synaptic terminals, due to the patchy distribution and short path-lengths observed. Our results thus highlight the need for exploring alternative roles for myelin in neocortical circuits.

Data availability

The following previously published data sets were used

Article and author information

Author details

  1. Kristina D Micheva

    Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States
    For correspondence
    kmicheva@stanford.edu
    Competing interests
    Kristina D Micheva, Have founder's equity interests in Aratome, LLC (Menlo Park, CA), an enterprise that produces array tomography materials and services. Also listed as inventors on two US patents regarding array tomography methods that have been issued to Stanford University (US patents 7,767,414 and 9,008,378).

  2. Dylan Wolman

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5012-1690

  3. Brett D Mensh

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.

  4. Elizabeth Pax

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.

  5. JoAnn Buchanan

    Allen Institute for Brain Science, Seattle, United States
    Competing interests
    No competing interests declared.

  6. Stephen J Smith

    Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States
    Competing interests
    Stephen J Smith, Have founder's equity interests in Aratome, LLC (Menlo Park, CA), an enterprise that produces array tomography materials and services. Also listed as inventors on two US patents regarding array tomography methods that have been issued to Stanford University (US patents 7,767,414 and 9,008,378).

  7. Davi D Bock

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    bockd@janelia.hhmi.org
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8218-7926

Ethics

Animal experimentation: The tissue for the array tomography experiments was provided by Dr. Richard Weinberg, University of North Carolina (UNC). All animal procedures were performed according to NIH and UNC guidelines with a protocol (#13-258.0) approved by the UNC Institutional Animal Care and Use Committee. Mice were housed in an approved UNC animal care facility on a 12-hour light/dark cycle with ad libitum food and water access. Immediately before the terminal surgery, mice were transported to the research laboratory, where they were deeply anesthetized with sodium pentobarbital (80 mg/kg ip). JRC Immunohistochemistry: Mice were housed on a 12-hour light/dark cycle with ad libitum food and water access. Experimental procedures were conducted according to the National Institute of Health guidelines for animal research and approved by the Institutional Animal Care and Use Committee at Janelia Farm Research Campus. Approved animal protocol is IACUC 11-71.

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Publication history

  1. Received: March 4, 2016
  2. Accepted: July 5, 2016
  3. Accepted Manuscript published: July 6, 2016 (version 1)
  4. Version of Record published: August 3, 2016 (version 2)

Copyright

© 2016, Micheva 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.

Metrics

  • 5,040
    Page views
  • 1,232
    Downloads
  • 115
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation

    Filip Sobczak et al.
    Research Article Updated

    Pupil dynamics serve as a physiological indicator of cognitive processes and arousal states of the brain across a diverse range of behavioral experiments. Pupil diameter changes reflect brain state fluctuations driven by neuromodulatory systems. Resting-state fMRI (rs-fMRI) has been used to identify global patterns of neuronal correlation with pupil diameter changes; however, the linkage between distinct brain state-dependent activation patterns of neuromodulatory nuclei with pupil dynamics remains to be explored. Here, we identified four clusters of trials with unique activity patterns related to pupil diameter changes in anesthetized rat brains. Going beyond the typical rs-fMRI correlation analysis with pupil dynamics, we decomposed spatiotemporal patterns of rs-fMRI with principal component analysis (PCA) and characterized the cluster-specific pupil–fMRI relationships by optimizing the PCA component weighting via decoding methods. This work shows that pupil dynamics are tightly coupled with different neuromodulatory centers in different trials, presenting a novel PCA-based decoding method to study the brain state-dependent pupil–fMRI relationship.

    1. Neuroscience

    Task-specific roles of local interneurons for inter- and intraglomerular signaling in the insect antennal lobe

    Debora Fusca, Peter Kloppenburg
    Research Article

    Local interneurons (LNs) mediate complex interactions within the antennal lobe, the primary olfactory system of insects, and the functional analog of the vertebrate olfactory bulb. In the cockroach Periplaneta americana, as in other insects, several types of LNs with distinctive physiological and morphological properties can be defined. Here, we combined whole-cell patch-clamp recordings and Ca2+ imaging of individual LNs to analyze the role of spiking and nonspiking LNs in inter- and intraglomerular signaling during olfactory information processing. Spiking GABAergic LNs reacted to odorant stimulation with a uniform rise in [Ca2+]i in the ramifications of all innervated glomeruli. In contrast, in nonspiking LNs, glomerular Ca2+ signals were odorant specific and varied between glomeruli, resulting in distinct, glomerulus-specific tuning curves. The cell type-specific differences in Ca2+ dynamics support the idea that spiking LNs play a primary role in interglomerular signaling, while they assign nonspiking LNs an essential role in intraglomerular signaling.

    1. Neuroscience

    Dendritic osmosensors modulate activity-induced calcium influx in oxytocinergic magnocellular neurons of the mouse PVN

    Wanhui Sheng et al.
    Research Article Updated

    Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not constant, but the mechanisms through which this relationship can be modulated are not completely understood. Here, we use a combination of electrical and optical recording techniques to quantify activity-induced calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes; however, activity-induced dendritic calcium influx can be robustly regulated by both osmosensitive and non-osmosensitive ion channels located along the dendritic membrane. Overall, this study reveals that dendritic conductivity is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release.