A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons
- Stanford University, United States
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- Allen Institute for Brain Science, United States
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
-
Network anatomy and in vivo physiology of visual cortical neurons.Publicly available at the Open Connectome Project (Mouse V1; http://openconnecto.me/bock11/).
Article and author information
Author details
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.
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
-
- 6,394
- views
-
- 1,423
- downloads
-
- 225
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons
eLife 5:e15784.
https://doi.org/10.7554/eLife.15784
Further reading
-
- Neuroscience
Life histories of oviparous species dictate high metabolic investment in the process of gonadal development leading to ovulation. In vertebrates, these two distinct processes are controlled by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively. While it was suggested that a common secretagogue, gonadotropin-releasing hormone (GnRH), oversees both functions, the generation of loss-of-function fish challenged this view. Here, we reveal that the satiety hormone cholecystokinin (CCK) is the primary regulator of this axis in zebrafish. We found that FSH cells express a CCK receptor, and our findings demonstrate that mutating this receptor results in a severe hindrance to ovarian development. Additionally, it causes a complete shutdown of both gonadotropins secretion. Using in-vivo and ex-vivo calcium imaging of gonadotrophs, we show that GnRH predominantly activates LH cells, whereas FSH cells respond to CCK stimulation, designating CCK as the bona fide FSH secretagogue. These findings indicate that the control of gametogenesis in fish was placed under different neural circuits, that are gated by CCK.
-
- Neuroscience
Neural diversity can expand the encoding capacity of a circuitry. A striking example of diverse structure and function is presented by the afferent synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea. Presynaptic active zones at the pillar IHC side activate at lower IHC potentials than those of the modiolar side that have more presynaptic Ca2+ channels. The postsynaptic SGNs differ in their spontaneous firing rates, sound thresholds, and operating ranges. While a causal relationship between synaptic heterogeneity and neural response diversity seems likely, experimental evidence linking synaptic and SGN physiology has remained difficult to obtain. Here, we aimed at bridging this gap by ex vivo paired recordings of murine IHCs and postsynaptic SGN boutons with stimuli and conditions aimed to mimic those of in vivo SGN characterization. Synapses with high spontaneous rate of release (SR) were found predominantly on the pillar side of the IHC. These high SR synapses had larger and more temporally compact spontaneous EPSCs, lower voltage thresholds, tighter coupling of Ca2+ channels and vesicular release sites, shorter response latencies, and higher initial release rates. This study indicates that synaptic heterogeneity in IHCs directly contributes to the diversity of spontaneous and sound-evoked firing of SGNs.
