Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex - PubMed (original) (raw)

Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex

Giulio Srubek Tomassy et al. Science. 2014.

Abstract

Myelin is a defining feature of the vertebrate nervous system. Variability in the thickness of the myelin envelope is a structural feature affecting the conduction of neuronal signals. Conversely, the distribution of myelinated tracts along the length of axons has been assumed to be uniform. Here, we traced high-throughput electron microscopy reconstructions of single axons of pyramidal neurons in the mouse neocortex and built high-resolution maps of myelination. We find that individual neurons have distinct longitudinal distribution of myelin. Neurons in the superficial layers displayed the most diversified profiles, including a new pattern where myelinated segments are interspersed with long, unmyelinated tracts. Our data indicate that the profile of longitudinal distribution of myelin is an integral feature of neuronal identity and may have evolved as a strategy to modulate long-distance communication in the neocortex.

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Figures

Fig. 1

Fig. 1. Radial distribution of myelin in the adult mouse neocortex

(A) Immunohistochemical staining of MBP and CUX1 in coronal sections of wild type adult neocortex. High magnifications of boxed areas show reduced levels of myelin in layer II/III (brackets). (B) PMAS lengths (arrowheads) in Golgi-Cox-labeled adult wild type cortex. Top, representative neurons in layer II/III and layer V. Bottom, scatter plot of PMAS length versus distance of neuronal cell bodies from the pia (n=72, R2= 0.61093). (C) 3D renderings of three representative neurons. The green and blue neurons were located in layer III–IV and the red neuron was in layer V. Myelin is shown in white. Ctx, cortex; Hip, hippocampus, Th, thalamus. Scale bars, 500 μm (A, low magnification), 100 μm (A, insets), 20 μm (B), 25 μm (C).

Fig. 2

Fig. 2. Layer II/III pyramidal neurons display novel profiles of longitudinal myelination including intermittent myelin

(A) High-resolution rendering of myelin distribution along single axons of 22 pyramidal neurons traced and reconstructed in layer II/III of the V1 dataset. Right panel, soma position and lengths of axonal tracts for all neurons rendered in left panel. Magenta, neurons with intermittent myelin; blue, neurons with long PMAS; green, neurons with unmyelinated axons; white, myelinated axonal segments. (B) Representative, serial EM reconstructions of neurons with long PMAS (left) or intermittent myelin (right). Unmyelinated axon tracts are highlighted in green and myelinated tracts in magenta. Insets, EM images and schematic representations of selected regions from each axon. Yellow, selected synapses mapped on the intermittently myelinated axon. Ax, axon; Nu, nucleus, Psd, post-synaptic density. (C) High-resolution rendering of three representative neurons displaying different myelination modes. Native positions of these neurons are preserved in the rendering. Arrowheads mark the boundaries of myelinated tracts (white). Scale bars, 50 μm (A), 2 μm (B), 0.5 μm (B, insets), 20 μm (C).

Fig. 3

Fig. 3. Longitudinal myelination profile is independent of neuron size and availability of oligodendrocyte progenitors

(A) Rendering and volumetric measurements of 283 pyramidal neurons across all layers of the S1 dataset. Soma size is color-coded with largest and smallest neurons rendered in orange and blue, respectively. Center, scatter plot of soma volumes versus distances from the pia. Top right, average values of the soma volumes measured in each cortical layer. Bottom right, scatter plot of PMAS lengths in layer V and VI versus cell body volumes. (B) Average values of soma volumes of 22 neurons from the V1 dataset, grouped according to their myelination profiles. (C) Top, immunohistochemistry for SOX10 and in situ hybridization for Pdgfrα in P14 wild type cortex. Right, quantification of OPCs distribution across layers. Bottom, in situ hybridization for Plp1 and immunohistochemistry for APC in adult wild type cortex. Right, quantification of OL distribution across layers. Error bars, mean±s.e.m. Ctx, cortex; wm, white matter; Str, striatum. Scale bars, 150 μm (A), 200 μm (C).

Fig. 4

Fig. 4. Distribution of myelin depends on the laminar position of distinct classes of projection neurons

Histological staining of myelin by Black Gold (BG) II and immunohistochemistry for CUX1, CTIP2, MBP and APC in P28 cortex of wild type (A), Dab1−/− (B) and Emx1-Cre;RhoAfl/fl (C) mice. Immunohistochemistry for APC is on immediately consecutive sections. (C) Upper insets, deep layer neuron heterotopias and myelin distribution in normocortex. Lower insets, myelin deposition in the SBH. Ac, anterior commissure; Ctx, cortex; SBH, subcortical band heterotopia; Str, striatum; wm, white matter. Scale bars, 400 μm (A–C, lower magnification panels), 200 μm (A–C, insets).

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References

    1. Baumann N, Pham-Dinh D. Physiol Rev. 2001;81:871. - PubMed
    1. Hildebrand C, Remahl S, Persson H, Bjartmar C. Prog Neurobiol. 1993;40:319. - PubMed
    1. Helmstaedter M, et al. Nature. 2013;500:168. - PubMed
    1. Lichtman JW, Denk W. Science. 2011;334:618. - PubMed
    1. Ramón y Cajal S. History of neuroscience. Oxford University Press; New York: 1995. Histology of the nervous system of man and vertebrates.

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