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Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination

Call, Cody L., Bergles, Dwight E.·2021·Nature Communications
DOI 10.1038/s41467-021-25035-2PMC PMC8346564
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Abstract

Axons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.

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Figures

Fig. 1 High-resolution tracing of distinct axon populations reveals discontinuous myelination patterns. a Schematic of the cortex indicating the sources of axons from the distinct neuronal populations investigated. Note that the axons depicted may not necessarily be the primary projection of each neuron. b A horizontal section of the entire cortical flatmount and schematic representing approximate cortical areas. N = 4 mice per neuron subtype. c Schematic of experimental design. Traces (black dotted line) of fluorescently labeled axons (red) were used to trace corresponding MBP-immunostained myelin sheaths (cyan). d–I Full reconstructions of traced PV (d), RBP4 (g), and VM (j) axons within cortical layer I and their associated dimensions (PLM, percent length myelinated). Black myelin sheaths are overlaid on colored axons. Labeled rectangles highlight example myelinated segments of PV (e, f), RBP4 (h, i), and VM (k, l) axons. Yellow arrowheads indicate the ends of myelin segments (MBP immunoreactivity). n = 60 (PV), 62 (VM), 60 (SOM), 61 (PO), 60 (NXPH4), 78 (RBP4), 60 (NTSR1) axons. Scale bars, b, 1 mm; d, g, j: 100 μm; e, f, h, i, k, l: 10 μm. OB olfactory bulb, lot lateral olfactory tract, MOp/MOs primary/secondary motor, ACA anterior cingulate area, GU/VISC gustatory/visceral, SSp/SSs primary/secondary somatosensory, PTLp posterior parietal association, AUD auditory, RSP retrosplenial, VISp primary visual, ECT/PERI ectorhinal/perirhinal, TEa temporal association.
Fig. 1 High-resolution tracing of distinct axon populations reveals discontinuous myelination patterns. a Schematic of the cortex indicating the sources of axons from the distinct neuronal populations investigated. Note that the axons depicted may not necessarily be the primary projection of each neuron. b A horizontal section of the entire cortical flatmount and schematic representing approximate cortical areas. N = 4 mice per neuron subtype. c Schematic of experimental design. Traces (black dotted line) of fluorescently labeled axons (red) were used to trace corresponding MBP-immunostained myelin sheaths (cyan). d–I Full reconstructions of traced PV (d), RBP4 (g), and VM (j) axons within cortical layer I and their associated dimensions (PLM, percent length myelinated). Black myelin sheaths are overlaid on colored axons. Labeled rectangles highlight example myelinated segments of PV (e, f), RBP4 (h, i), and VM (k, l) axons. Yellow arrowheads indicate the ends of myelin segments (MBP immunoreactivity). n = 60 (PV), 62 (VM), 60 (SOM), 61 (PO), 60 (NXPH4), 78 (RBP4), 60 (NTSR1) axons. Scale bars, b, 1 mm; d, g, j: 100 μm; e, f, h, i, k, l: 10 μm. OB olfactory bulb, lot lateral olfactory tract, MOp/MOs primary/secondary motor, ACA anterior cingulate area, GU/VISC gustatory/visceral, SSp/SSs primary/secondary somatosensory, PTLp posterior parietal association, AUD auditory, RSP retrosplenial, VISp primary visual, ECT/PERI ectorhinal/perirhinal, TEa temporal association.CC BY · PubMed Central
Fig. 2 Different neuronal subtypes exhibit diverse myelination profiles. a Myelination profiles for the six neuronal subtypes examined in this study with myelinated axons. Each plot is a histogram of pooled data across four animals for each subtype representing the proportion of axons with different percent length myelinated in 10% bins (n = 60 (PV), 62 (VM), 60 (SOM), 61 (PO), 60 (NXPH4), 78 (RBP4), 60 (NTSR1) axons). See Table 2 for statistical comparisons. b Cumulative distribution plot of data in (a), showing three distinct classes of myelination patterns. c Proportions of axons myelinated per neuronal subtype (N = 4 mice for each subtype) ****p < 0.0001. d Lengths for each axon traced (same Ns as in (a)). e Average internode lengths per axon for each neuronal subtype (n = 38 (PV), 41 (VM), 18 (SOM), 14 (PO), 6 (NXPH4), 2 (NTSR1) axons) (ns, not significant, p = 0.514, one-way ANOVA). f Violin plots of the lengths of unmyelinated axon segments (axonal distance between two consecutive MBP segments) for the top four most strongly myelinated neuronal subtypes. Unmyelinated segments of <5 μm (typical maximum length of nodes of Ranvier) are most common, while unmyelinated segments between 5 and 150 μm distributed broadly. g Cumulative distribution plot of all non-nodal (>5 μm) unmyelinated segments from data in f. All error bars represent the standard error of the mean. Source data and statistical tests are provided as a Source Data file.
Fig. 2 Different neuronal subtypes exhibit diverse myelination profiles. a Myelination profiles for the six neuronal subtypes examined in this study with myelinated axons. Each plot is a histogram of pooled data across four animals for each subtype representing the proportion of axons with different percent length myelinated in 10% bins (n = 60 (PV), 62 (VM), 60 (SOM), 61 (PO), 60 (NXPH4), 78 (RBP4), 60 (NTSR1) axons). See Table 2 for statistical comparisons. b Cumulative distribution plot of data in (a), showing three distinct classes of myelination patterns. c Proportions of axons myelinated per neuronal subtype (N = 4 mice for each subtype) ****p < 0.0001. d Lengths for each axon traced (same Ns as in (a)). e Average internode lengths per axon for each neuronal subtype (n = 38 (PV), 41 (VM), 18 (SOM), 14 (PO), 6 (NXPH4), 2 (NTSR1) axons) (ns, not significant, p = 0.514, one-way ANOVA). f Violin plots of the lengths of unmyelinated axon segments (axonal distance between two consecutive MBP segments) for the top four most strongly myelinated neuronal subtypes. Unmyelinated segments of <5 μm (typical maximum length of nodes of Ranvier) are most common, while unmyelinated segments between 5 and 150 μm distributed broadly. g Cumulative distribution plot of all non-nodal (>5 μm) unmyelinated segments from data in f. All error bars represent the standard error of the mean. Source data and statistical tests are provided as a Source Data file.CC BY · PubMed Central
Fig. 3 PV axon myelination patterns are consistent across cortical regions. a Representative binarized images of MBP immunostaining from all cortical regions analyzed (SS somatosensory, AUD auditory, VIS visual, MOs secondary motor, TEa temporal association area). Scale bars, 50 μm. b Example axon and myelin traces from each cortical region analyzed from a single PV-Cre; Ai9 flatmount. Red, axons; white, myelin. Scale bars, 50 μm. c Cumulative distribution plot of PLM from all axons traced in each region in a (SS, n = 60 axons from 4 mice; VIS, n = 60 axons from 4 mice; AUD, n = 59 axons from 4 mice; MOs, N = 30 axons from 2 mice; TEa, N = 37 axons from 3 mice). See Table 3 for PLM distribution statistics. d Scaled prevalence (MBP intensity/proportion of axons myelinated) of PV axon myelination across all regions analyzed (same Ns as in c) (ns not significant, p = 0.24, Kruskal–Wallis ANOVA). Error bars represent the standard error of the mean. Source data and statistical tests are provided as a Source Data file.
Fig. 3 PV axon myelination patterns are consistent across cortical regions. a Representative binarized images of MBP immunostaining from all cortical regions analyzed (SS somatosensory, AUD auditory, VIS visual, MOs secondary motor, TEa temporal association area). Scale bars, 50 μm. b Example axon and myelin traces from each cortical region analyzed from a single PV-Cre; Ai9 flatmount. Red, axons; white, myelin. Scale bars, 50 μm. c Cumulative distribution plot of PLM from all axons traced in each region in a (SS, n = 60 axons from 4 mice; VIS, n = 60 axons from 4 mice; AUD, n = 59 axons from 4 mice; MOs, N = 30 axons from 2 mice; TEa, N = 37 axons from 3 mice). See Table 3 for PLM distribution statistics. d Scaled prevalence (MBP intensity/proportion of axons myelinated) of PV axon myelination across all regions analyzed (same Ns as in c) (ns not significant, p = 0.24, Kruskal–Wallis ANOVA). Error bars represent the standard error of the mean. Source data and statistical tests are provided as a Source Data file.CC BY · PubMed Central
Fig. 4 A combination of diameter and neuronal subtype predicts myelination status. a Example segment of an axon imaged at high resolution for diameter analysis and corresponding MBP immunostaining. A small rectangle was used to plot a profile of the average gray value intensity profile across a few μm of the axon (result shown in (b)) to determine its diameter by the full width at half maximum (FWHM). Scale bar, 2 μm. b Plot of the average profile across the axon in (a). Each point represents the average gray value of a single pixel across the representative lines in (a), top panel. c Histograms of the proportions of axons myelinated (colored bars) or unmyelinated (gray bars) for different axon diameters. Note the color of overlapping bars is additive. d As in (c), pooled across all neuronal subtypes. e Probability distributions for the myelination probability of each neuronal subtype given a certain diameter. Points are individual axons myelinated. Intermediate probabilities (not 1 or 0) represent the average myelination status across at least three positions along the axon surveyed to calculate the average diameter. See text for details on probability functions. Source data and statistical tests are provided as a Source Data file.
Fig. 4 A combination of diameter and neuronal subtype predicts myelination status. a Example segment of an axon imaged at high resolution for diameter analysis and corresponding MBP immunostaining. A small rectangle was used to plot a profile of the average gray value intensity profile across a few μm of the axon (result shown in (b)) to determine its diameter by the full width at half maximum (FWHM). Scale bar, 2 μm. b Plot of the average profile across the axon in (a). Each point represents the average gray value of a single pixel across the representative lines in (a), top panel. c Histograms of the proportions of axons myelinated (colored bars) or unmyelinated (gray bars) for different axon diameters. Note the color of overlapping bars is additive. d As in (c), pooled across all neuronal subtypes. e Probability distributions for the myelination probability of each neuronal subtype given a certain diameter. Points are individual axons myelinated. Intermediate probabilities (not 1 or 0) represent the average myelination status across at least three positions along the axon surveyed to calculate the average diameter. See text for details on probability functions. Source data and statistical tests are provided as a Source Data file.CC BY · PubMed Central
Fig. 5 Overall subtype-specific myelination patterns are restored despite remodeling of individual axons. a Experimental timeline. b Example image from a PV-Cre; Ai9 mouse injected with AAV-EGFP into thalamic VM. SCoRe signal from the same region is overlaid on top of the fluorescent dual-colored image acquired with two-photon microscopy. Right panel shows a few myelinated axons of both neuronal subtypes extracted from the left panel. Scale bar, 30 μm. c Axon traces from an example 3-week cuprizone timecourse. Left panel shows PV axon traces (white) and the associated myelin segments traced from the corresponding SCoRe image (magenta). Right panel shows same region with the surviving baseline axon traces overlaid with the positions of SCoRe segments traced at 5 weeks of recovery (green). Yellow arrowhead indicates example axon that had a net loss in length myelinated, while the cyan arrowhead indicates a portion of axon which gained myelination. Scale bar, 100 μm. d, Pooled data from remyelinated PV and VM axons showing the net change in PLM between baseline and 5 weeks recovery where –100% represents an axon going from fully myelinated to fully unmyelinated, and +100% represents an axon that went from unmyelinated to fully myelinated. Dashed lines bordering 0% (solid line) reflect the tracing error as calculated by the average negative ΔPLM from axons of the respective subtype traced in control animals (Supplemental Fig. 2, see text for additional details). e and f Scatter plots showing the relationship between the PLM of an axon at baseline and its PLM at five weeks recovery from cuprizone for PV axons (e) and VM axons (f). The solid red line (y = x) is the identity line (no change between baseline and 5 weeks recovery) and the red dashed lines are the error based on control traces (as in (d)). The black line is the best fit found by regression and the black dotted lines are the 95% confidence bounds. g and h Data as plotted in (e, f) readjusted to include the ΔPLM of each axon in the linear model (adjusted formula: PLM at 5 weeks recovery ~ 1 + baseline PLM + baseline PLM: ΔPLM; g, PV axons; h VM axons). The solid line is the fit and dotted lines are the 95% confidence bounds. Source data and statistical tests are provided as a Source Data file.
Fig. 5 Overall subtype-specific myelination patterns are restored despite remodeling of individual axons. a Experimental timeline. b Example image from a PV-Cre; Ai9 mouse injected with AAV-EGFP into thalamic VM. SCoRe signal from the same region is overlaid on top of the fluorescent dual-colored image acquired with two-photon microscopy. Right panel shows a few myelinated axons of both neuronal subtypes extracted from the left panel. Scale bar, 30 μm. c Axon traces from an example 3-week cuprizone timecourse. Left panel shows PV axon traces (white) and the associated myelin segments traced from the corresponding SCoRe image (magenta). Right panel shows same region with the surviving baseline axon traces overlaid with the positions of SCoRe segments traced at 5 weeks of recovery (green). Yellow arrowhead indicates example axon that had a net loss in length myelinated, while the cyan arrowhead indicates a portion of axon which gained myelination. Scale bar, 100 μm. d, Pooled data from remyelinated PV and VM axons showing the net change in PLM between baseline and 5 weeks recovery where –100% represents an axon going from fully myelinated to fully unmyelinated, and +100% represents an axon that went from unmyelinated to fully myelinated. Dashed lines bordering 0% (solid line) reflect the tracing error as calculated by the average negative ΔPLM from axons of the respective subtype traced in control animals (Supplemental Fig. 2, see text for additional details). e and f Scatter plots showing the relationship between the PLM of an axon at baseline and its PLM at five weeks recovery from cuprizone for PV axons (e) and VM axons (f). The solid red line (y = x) is the identity line (no change between baseline and 5 weeks recovery) and the red dashed lines are the error based on control traces (as in (d)). The black line is the best fit found by regression and the black dotted lines are the 95% confidence bounds. g and h Data as plotted in (e, f) readjusted to include the ΔPLM of each axon in the linear model (adjusted formula: PLM at 5 weeks recovery ~ 1 + baseline PLM + baseline PLM: ΔPLM; g, PV axons; h VM axons). The solid line is the fit and dotted lines are the 95% confidence bounds. Source data and statistical tests are provided as a Source Data file.CC BY · PubMed Central
Fig. 6 PV axons are not preferentially remyelinated in regions with reduced oligodendrogenesis. a In vivo image of layer II/III somatosensory cortex acquired from a Mobp-EGFP; PV-Cre; Ai9 mouse. Yellow arrowheads identify example sheaths surrounding PV axons, while magenta arrowheads identify sheaths surrounding non-PV axons (“other”). Scale bar, 10 μm. b Example maximum XZ projection of an ROI (100 μm × 100 μm × 100 μm) from layer II/III showing all traced internodes within the volume at baseline (left) and at 5 weeks recovery from cuprizone (right). Red, sheaths surrounding PV axons; black, sheaths surrounding “other” axons. Scale bar, 20 μm. c Total number of internodes within an ROI at baseline vs. 5 weeks recovery (n = 10 ROIs (up to 2 ROIs from 2 imaged regions across 3 mice)) (**p = 0.003, paired two-tailed t-test). d Percent of traced sheaths surrounding PV axons within an ROI at baseline vs. 5 weeks recovery, same Ns as in c (ns, not significant, p = 0.068, paired two-tailed t-test). All error bars represent standard error of the mean. Source data and statistical tests are provided as a Source Data file.
Fig. 6 PV axons are not preferentially remyelinated in regions with reduced oligodendrogenesis. a In vivo image of layer II/III somatosensory cortex acquired from a Mobp-EGFP; PV-Cre; Ai9 mouse. Yellow arrowheads identify example sheaths surrounding PV axons, while magenta arrowheads identify sheaths surrounding non-PV axons (“other”). Scale bar, 10 μm. b Example maximum XZ projection of an ROI (100 μm × 100 μm × 100 μm) from layer II/III showing all traced internodes within the volume at baseline (left) and at 5 weeks recovery from cuprizone (right). Red, sheaths surrounding PV axons; black, sheaths surrounding “other” axons. Scale bar, 20 μm. c Total number of internodes within an ROI at baseline vs. 5 weeks recovery (n = 10 ROIs (up to 2 ROIs from 2 imaged regions across 3 mice)) (**p = 0.003, paired two-tailed t-test). d Percent of traced sheaths surrounding PV axons within an ROI at baseline vs. 5 weeks recovery, same Ns as in c (ns, not significant, p = 0.068, paired two-tailed t-test). All error bars represent standard error of the mean. Source data and statistical tests are provided as a Source Data file.CC BY · PubMed Central

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Research works printed but not linked: 74

  1. Cauller, L. Layer I of primary sensory neocortex: where top-down converges upon bottom-up. Behav. Brain Res. 71, 163–170 (1995). · DOI
  2. Xu, N. L. et al. Nonlinear dendritic integration of sensory and motor input during an active sensing task. Nature. 492, 247–251 (2021). · DOI
  3. Cruikshank, S. J. et al. Thalamic control of layer 1 circuits in prefrontal cortex. J. Neurosci. 32, 17813–17823 (2012). · DOI · Paper page
  4. Cauller, L. J., Clancy, B. & Connors, B. W. Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I. J. Comp. Neurol. 390, 297–310 (1998). · DOI
  5. Rubio-Garrido, P., Pérez-De-Manzo, F., Porrero, C., Galazo, M. J. & Clascá, F. Thalamic input to distal apical dendrites in neocortical layer 1 is massive and highly convergent. Cereb. Cortex 19, 2380–2395 (2009). · DOI
  6. Zilles, K., Palomero-Gallagher, N. & Amunts, K. Myeloarchitecture and maps of the cerebral cortex. In Brain Mapping: An Encyclopedic Reference (ed. Toga, A. W.) Vol. 2 137–156 (Elsevier Inc., 2015). · DOI
  7. Micheva, K. D. et al. A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons. Elife 5, 1–29 (2016). · DOI
  8. Stedehouder, J. et al. Fast-spiking parvalbumin interneurons are frequently myelinated in the cerebral cortex of mice and humans. Cereb. Cortex 27, 5001–5013 (2017). · DOI
  9. Hill, R. A., Li, A. M. & Grutzendler, J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nat. Neurosci. 21, 683–695 (2018). · DOI · Paper page
  10. Hughes, E. G., Orthmann-Murphy, J. L., Langseth, A. J. & Bergles, D. E. Myelin remodeling through experience-dependent oligodendrogenesis in the adult somatosensory cortex. Nat. Neurosci. 21, 696–706 (2018). · DOI · Paper page
  11. Tomassy, G. S. et al. Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex. Science 344, 319–324 (2014). · DOI · Paper page
  12. Voyvodic, J. T. Target size regulates calibre and myelination of sympathetic axons. Nature 342, 430–433 (1989). · DOI
  13. Elder, G. A., Friedrich, V. L. & Lazzarini, R. A. Schwann cells and oligodendrocytes read distinct signals in establishing myelin sheath thickness. J. Neurosci. Res. 65, 493–499 (2001). · DOI
  14. Schröder, J. M., Bohl, J. & Brodda, K. Changes of the ratio between myelin thickness and axon diameter in the human developing sural nerve. Acta Neuropathol. 43, 169–178 (1978). · DOI
  15. Bechler, M. E., Byrne, L. & Ffrench-Constant, C. CNS myelin sheath lengths are an intrinsic property of oligodendrocytes. Curr. Biol. 25, 2411–2416 (2015). · DOI
  16. Mayoral, S. R., Etxeberria, A., Shen, Y.-A. A. A. A. & Chan, J. R. Initiation of CNS myelination in the optic nerve is dependent on axon caliber. Cell Rep. 25, 544–550e3 (2018). · DOI
  17. Remahl, S. & Hildebrand, C. Changing relation between onset of myelination and axon diameter range in developing feline white matter. J. Neurol. Sci. 54, 33–45 (1982). · DOI
  18. Waxman, S. G. & Sims, T. J. Specificity in central myelination: evidence for local regulation of myelin thickness. Brain Res. 292, 179–185 (1984). · DOI
  19. Chong, S. Y. C. et al. Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination. Proc. Natl Acad. Sci. USA 109, 1299–1304 (2012). · DOI · Paper page
  20. Demerens, C. et al. Induction of myelination in the central nervous system by electrical activity. Proc. Natl Acad. Sci. USA 93, 9887–9892 (1996). · DOI · Paper page
  21. Stevens, B., Porta, S., Haak, L. L., Gallo, V. & Fields, R. D. Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials. Neuron 36, 855–868 (2002). · DOI
  22. Gibson, E. M. et al. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science 344, 1252304 (2014). · DOI · Paper page
  23. Redmond, S. A. et al. Somatodendritic expression of JAM2 inhibits oligodendrocyte myelination. Neuron 91, 824–836 (2016). · DOI
  24. Bø, L., Vedeler, C. A., Nyland, H. I., Trapp, B. D. & Mørk, S. J. Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J. Neuropathol. Exp. Neurol. 62, 723–732 (2003). · DOI · Paper page
  25. Howell, O. W. et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 134, 2755–2771 (2011). · DOI · Paper page
  26. Kidd, D. et al. Cortical lesions in multiple sclerosis. Brain 122(Part 1), 17–26 (1999). · DOI · Paper page
  27. Roosendaal, S. et al. Accumulation of cortical lesions in MS: relation with cognitive impairment. Mult. Scler. J. 15, 708–714 (2009). · DOI
  28. Nielsen, A. S. et al. Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS. Neurology 81, 641–649 (2013). · DOI
  29. Sacco, R. et al. Cognitive impairment and memory disorders in relapsing–remitting multiple sclerosis: the role of white matter, gray matter and hippocampus. J. Neurol. 262, 1691–1697 (2015). · DOI
  30. Muhlert, N. et al. The grey matter correlates of impaired decision-making in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 86, 530–536 (2015). · DOI
  31. Zonouzi, M. et al. Individual oligodendrocytes show bias for inhibitory axons in the neocortex. Cell Reports 27, 2799–2808 (2019). · DOI
  32. Stedehouder, J. & Kushner, S. A. Myelination of parvalbumin interneurons: a parsimonious locus of pathophysiological convergence in schizophrenia. Mol. Psychiatry 22, 4–12 (2017). · DOI
  33. Denman, D. J. & Contreras, D. Complex effects on in vivo visual responses by specific projections from mouse cortical layer 6 to dorsal lateral geniculate nucleus. J. Neurosci. 35, 9265–9280 (2015). · DOI
  34. Bortone, D. S., Olsen, S. R. & Scanziani, M. Translaminar inhibitory cells recruited by layer 6 corticothalamic neurons suppress visual cortex. Neuron 82, 474–485 (2014). · DOI · Paper page
  35. Viswanathan, S., Sheikh, A., Looger, L. L. & Kanold, P. O. Molecularly defined subplate neurons project both to thalamocortical recipient layers and thalamus. Cereb. Cortex 27, 4759–4768 (2017).
  36. Clancy, B. & Cauller, L. J. Widespread projections from subgriseal neurons (layer VII) to layer I in adult rat cortex. J. Comp. Neurol. 407, 275–286 (1999). · DOI
  37. Ibrahim, L. A. et al. Cross-modality sharpening of visual cortical processing through layer-1-mediated inhibition and disinhibition. Neuron 89, 1031–1045 (2016). · DOI
  38. Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 (2010). · DOI · Paper page
  39. Gong, S. et al. Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs. J. Neurosci. 27, 9817–9823 (2007). · DOI · Paper page
  40. Harris, J. A. et al. Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation. Front. Neural Circuits. 8, 76 (2014). · DOI · Paper page
  41. Hunt, B. A. E. et al. Relationships between cortical myeloarchitecture and electrophysiological networks. Proc. Natl Acad. Sci. USA 113, 13510–13515 (2016). · DOI
  42. Nieuwenhuys, R. & Broere, C. A. J. A detailed comparison of the cytoarchitectonic and myeloarchitectonic maps of the human neocortex produced by the Vogt–Vogt school. Brain Struct. Funct. 1, 3 (2020).
  43. Whissell, P. D., Cajanding, J. D., Fogel, N. & Kim, J. C. Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus. Front. Neuroanat. 9, 124 (2015). · DOI · Paper page
  44. Stedehouder, J. et al. Local axonal morphology guides the topography of interneuron myelination in mouse and human neocortex. Elife 8, 1–28 (2019). · DOI
  45. Bacmeister, C. M. et al. Motor learning promotes remyelination via new and surviving oligodendrocytes. Nat. Neurosci. 23, 819–831 (2020). · DOI
  46. Schain, A. J., Hill, R. A. & Grutzendler, J. Label-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy. Nat. Med. 20, 443–449 (2014). · DOI
  47. Stedehouder, J., Brizee, D., Shpak, G. & Kushner, S. A. Activity-dependent myelination of parvalbumin interneurons mediated by axonal morphological plasticity. J. Neurosci. 38, 3631–3642 (2018). · DOI
  48. Lee, S. et al. A culture system to study oligodendrocyte myelination processes using engineered nanofibers. Nat. Methods 9, 917–922 (2012). · DOI
  49. Kang, S. H., Fukaya, M., Yang, J. K., Rothstein, J. D. & Bergles, D. E. NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. Neuron 68, 668–681 (2010). · DOI
  50. Almeida, R. G. The rules of attraction in central nervous system myelination. Front. Cell. Neurosci. 12, 367 (2018). · DOI
  51. Mi, S. et al. LINGO-1 negatively regulates myelination by oligodendrocytes. Nat. Neurosci. 8, 745–751 (2005). · DOI
  52. Linneberg, C., Harboe, M. & Laursen, L. S. Axo-glia interaction preceding CNS myelination is regulated by bidirectional Eph-ephrin signaling. ASN Neuro 7, 1–17 (2015). · DOI
  53. Brinkmann, B. G. et al. Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system. Neuron 59, 581–595 (2008). · DOI
  54. Zuchero, J. B. et al. CNS myelin wrapping is driven by actin disassembly. Dev. Cell 34, 152–167 (2015). · DOI · Paper page
  55. Snaidero, N. et al. Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth at the inner tongue. Cell 156, 277–290 (2014). · DOI
  56. Ishibashi, T. et al. Astrocytes promote myelination in response to electrical impulses. Neuron 49, 823–832 (2006). · DOI · Paper page
  57. Mitew, S. et al. Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner. Nat. Commun. 9, 1–16 (2018). · DOI
  58. Hines, J. H., Ravanelli, A. M., Schwindt, R., Scott, E. K. & Appel, B. Neuronal activity biases axon selection for myelination in vivo. Nat. Neurosci. 18, 683–689 (2015). · DOI
  59. Yang, S. M., Michel, K., Jokhi, V., Nedivi, E. & Arlotta, P. Neuron class-specific responses govern adaptive myelin remodeling in the neocortex. Science 370, eabd2109 (2021). · DOI
  60. Dutta, D. J. et al. Regulation of myelin structure and conduction velocity by perinodal astrocytes. Proc. Natl Acad. Sci. USA 115, 11832–11837 (2018). · DOI
  61. Hughes, E. G., Kang, S. H., Fukaya, M. & Bergles, D. E. Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat. Neurosci. 16, 668–676 (2013). · DOI · Paper page
  62. Ghanbari, L. et al. Cortex-wide neural interfacing via transparent polymer skulls. Nat. Commun. 10, 1500 (2019). · DOI
  63. Hamada, M. S. & Kole, M. H. P. Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability. J. Neurosci. 35, 7272–7286 (2015). · DOI
  64. Hamada, M. S., Popovic, M. A. & Kole, M. H. P. Loss of saltation and presynaptic action potential failure in demyelinated axons. Front. Cell. Neurosci. 11, 1–11 (2017). · DOI
  65. Werneburg, S. et al. Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease. Immunity 52, 167–182.e7 (2020). · DOI · Paper page
  66. Rankin, K. A. et al. Selective estrogen receptor modulators enhance CNS remyelination independent of estrogen receptors. J. Neurosci. 39, 2184–2194 (2019). · DOI
  67. Mei, F. et al. Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery. Elife 5, e18246 (2016). · DOI
  68. Mei, F. et al. Identification of the kappa-opioid receptor as a therapeutic target for oligodendrocyte remyelination. J. Neurosci. 36, 7925–7935 (2016). · DOI
  69. Taniguchi, H. et al. A resource of Cre driver lines for genetic targeting of GABAergic. Neurons Cereb. Cortex Neuron 71, 995–1013 (2011).
  70. Kang, S. H. et al. Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis. Nat. Neurosci. 16, 571–579 (2013). · DOI · Paper page
  71. Longair, M. H., Baker, D. A. & Armstrong, J. D. Simple Neurite Tracer: open source software for reconstruction, visualization and analysis of neuronal processes. Bioinformatics 27, 2453–2454 (2011). · DOI
  72. Papadopoulos, G. C., Parnavelas, J. G. & Buijs, R. M. Light and electron microscopic immunocytochemical analysis of the serotonin innervation of the rat visual cortex. J. Neurocytol. 16, 883–892 (1987). · DOI
  73. Papadopoulos, G. C., Parnavelas, J. G. & Buijs, R. M. Light and electron microscopic immunocytochemical analysis of the noradrenaline innervation of the rat visual cortex. J. Neurocytol. 18, 1–10 (1989). · DOI
  74. Papadopoulos, G. C., Parnavelas, J. G. & Buijs, R. M. Light and electron microscopic immunocytochemical analysis of the dopamine innervation of the rat visual cortex. J. Neurocytol. 18, 303–310 (1989). · DOI

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Metadata

Authors
Call, C. L., & Bergles, D. E.
ORCID
Bergles, Dwight E.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-08-06
Volume
12
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-021-25035-2
PMC
PMC8346564
Cited by
95
References
12
Language
en
Licence
Funders
Dr. Miriam and Sheldon G Adelson Medical Research Foundation

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