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Rapid Conduction and the Evolution of Giant Axons and Myelinated Fibers
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Nervous systems have evolved two basic mechanisms for increasing the conduction speed of the electrical impulse. The first is through axon gigantism: using axons several times larger in diameter than the norm for other large axons, as for example in the well-known case of the squid giant axon. The second is through encasing axons in helical or concentrically wrapped multilamellar sheets of insulating plasma membrane--the myelin sheath. Each mechanism, alone or in combination, is employed in nervous systems of many taxa, both vertebrate and invertebrate. Myelin is a unique way to increase conduction speeds along axons of relatively small caliber. It seems to have arisen independently in evolution several times in vertebrates, annelids and crustacea. Myelinated nerves, regardless of their source, have in common a multilamellar membrane wrapping, and long myelinated segments interspersed with 'nodal' loci where the myelin terminates and the nerve impulse propagates along the axon by 'saltatory' conduction. For all of the differences in detail among the morphologies and biochemistries of the sheath in the different myelinated animal classes, the function is remarkably universal.
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“Myelination enables rapid action potential conduction, provides essential trophic support to axons, and is required for learning, memory, and cognition.2,3,4,5”
From Neurons sequester the cholesterol-inhibiting TFEB in oligodendrocyte cytoplasm to safeguard myelination and neural function (2025) · cites this paper as [2]
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“Furthermore, within the peripheral nervous system, different nerve fibers conduct action potentials at different speeds [23], and variable frequency and duration [24], which can affect their tolerance to electrical stimulation regimes.”
From Safety of long-term electrical peripheral nerve stimulation: review of the state of the art (2019) · cites this paper as [23]
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BackgroundMarion, C. M., McDaniel, D. P., & Armstrong, R. C. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.113040 · Cited by 82
“Myelin enables rapid impulse firing and fast conduction of action potentials, and also provides trophic and metabolic support to axons (Hartline and Colman, 2007; Morrison et al., 2013; Nave, 2010).”
Möbius, W., Patzig, J., Nave, K., & Werner, H. B. (2008) · Neuron Glia Biology · doi:10.1017/s1740925x0900009x · Cited by 86
The visual white matter: The application of diffusion MRI and fiber tractography to vision science
Rokem, A., Takemura, H., Bock, A. S., Scherf, K. S., Behrmann, M., Wandell, B. A., Fine, I., Bridge, H., & Pestilli, F. (2017) · Journal of Vision · doi:10.1167/17.2.4 · Cited by 92
“Some types of glia (primarily oligodendrocytes) form an insulating layer around these axons (myelin sheaths) that allow the axons to transmit information more rapidly (Waxman and Bennett, 1972), and more accurately (Kim et al., 2013), and reduce their energy consumption (Hartline and Colman, 2007).”
BackgroundDevelopment of myelinating glia: An overview
Cristobal, C. D., & Lee, H. K. (2022) · Glia · doi:10.1002/glia.24238 · Cited by 85
“Myelin has been canonically known to facilitate saltatory conduction in axonal fibers and speed up electrical conduction (Hartline & Colman, 2007; Salzer et al., 2016; Zalc, 2016).”
BackgroundMyelination generates aberrant ultrastructure that is resolved by microglia
Djannatian, M., Radha, S., Weikert, U., Safaiyan, S., Wrede, C., Deichsel, C., Kislinger, G., Rhomberg, A., Ruhwedel, T., Campbell, D. S., et al. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202204010 · Cited by 102
“Myelin, produced by oligodendrocytes in the CNS, electrically insulates axons to facilitate saltatory conduction (Rushton, 1951; Cohen et al., 2020; Hartline and Colman, 2007) and also provides metabolic support (Fünfschilling et al.”
BackgroundMyelin architecture: zippering membranes tightly together
Bakhti, M., Aggarwal, S., & Simons, M. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1492-0 · Cited by 78
“Myelin evolved several times independently during evolution [1].”
Harzsch, S., & Krieger, J. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.11.005 · Cited by 82
“What is more, copepods have evolved their own form of myelin to increase the conduction speed in those motor fibers that drive the escape response (Hartline and Colman, 2007; Wilson and Hartline, 2011).”
Mechanisms of axonal support by oligodendrocyte-derived extracellular vesicles
Krämer‐Albers, E., & Werner, H. B. (2023) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00711-y · Cited by 83
Handedness, motor skills and maturation of the corticospinal tract in the adolescent brain
Hervé, P., Leonard, G. T., Perron, M., Pike, G. B., Pitiot, A., Richer, L., Veillette, S., Pausová, Z., & Paus, T. (2009) · Human Brain Mapping · doi:10.1002/hbm.20734 · Cited by 76
“Theoretically, larger axons on the dominant side would allow for faster conduction times [Hartline and Colman, 2007; Rushton, 1951] and/or increased axonal transport capacities [but Inestrosa and Alvarez, 1988]; yet, an increase in the axon diameter throughout adolescence was not shown to have any influence on motor s…”
BackgroundAuditory Nerve Perinodal Dysmyelination in Noise-Induced Hearing Loss
Tagoe, T. A., Barker, M., Jones, A., Allcock, N., & Hamann, M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3977-13.2014 · Cited by 77
“The elongation of the node (reflecting retraction of paranodal myelin) would increase the nodal capacitance, decrease its membrane resistance and therefore increase the time to reach threshold contributing to slowing the conduction velocity (Hartline and Colman, 2007).”
BackgroundErwig, M. S., Patzig, J., Steyer, A. M., Dibaj, P., Heilmann, M., Heilmann, I., Jung, R. B., Kusch, K., Möbius, W., Jahn, O., et al. (2019) · eLife · doi:10.7554/elife.43888 · Cited by 79
Death Valley, Drosophila, and the Devonian Toolkit
Dickinson, M. H. (2013) · Annual Review of Entomology · doi:10.1146/annurev-ento-011613-162041 · Cited by 73
Glial Cells—The Strategic Targets in Amyotrophic Lateral Sclerosis Treatment
Filipi, T., Heřmanová, Z., Turečková, J., Vaňátko, O., & Anděrová, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9010261 · Cited by 76
“Myelin plays an important role, not only in the electrical insulation of the axons, but also in their provision with trophic and metabolic support [199].”
BackgroundSimkins, T., Duncan, G. J., & BOURDETTE, D. N. (2021) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-021-01110-5 · Cited by 79
Kucenas, S., Snell, H. D., & Appel, B. (2008) · Neuron Glia Biology · doi:10.1017/s1740925x09990123 · Cited by 73
“N IH -PA Author M anuscript N IH -PA Author M anuscript general strategies have evolved to increase the speed of electrical impulse conduction and thereby facilitate escape (Hartline and Colman, 2007).”
BackgroundTowards in vivo g-ratio mapping using MRI: Unifying myelin and diffusion imaging
Mohammadi, S., & Callaghan, M. F. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.108990 · Cited by 72
“As the central nervous system appears to communicate at physical limits to constrain metabolic demands (Salami et al., 2003; Hartline and Colman, 2007; Coggan et al., 2015), small”
BackgroundScholl, T. O., Mühlebner, A., Ricken, G., Gruber, V., Fabing, A., Samueli, S., Gröppel, G., Dorfer, C., Czech, T., Hainfellner, J. A., et al. (2016) · Brain Pathology · doi:10.1111/bpa.12452 · Cited by 73
“In its lifetime, a single oligodendrocyte is able to enwrap axons of up to 50 neurons (14, 22, 28).”
BackgroundKottmeier, R., Bittern, J., Schoofs, A., Scheiwe, F., Matzat, T., Pankratz, M. J., & Klämbt, C. (2020) · Nature Communications · doi:10.1038/s41467-020-18291-1 · Cited by 74
Strategies for Oligodendrocyte and Myelin Repair in Traumatic CNS Injury
Huntemer-Silveira, A., Patil, N., Brickner, M. A., & Parr, A. M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.619707 · Cited by 72
“Another promising target is the repulsive guidance molecule A (RGMa), which accumulates in lesion sites of SCI (Schwab et al., 2005; Hata et al., 2006).”
BackgroundOligodendrocyte precursor cells as a therapeutic target for demyelinating diseases
Skaper, S. D. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.03.013 · Cited by 73
Molecular evolution of myelin basic protein, an abundant structural myelin component
Nawaz, S., Schweitzer, J., Jahn, O., & Werner, H. B. (2013) · Glia · doi:10.1002/glia.22520 · Cited by 72
Foster, A. Y., Bujalka, H., & Emery, B. (2019) · Glia · doi:10.1002/glia.23629 · Cited by 65
“2019;67:2038–2049. conduction (Xu & Terakawa, 1999)—the unique extent of myelin in the nervous system of jawed vertebrates almost certainly allowed the increase in size and complex behaviors seen in vertebrate species during evolution (Hartline & Colman, 2007; Zalc, 2016).”
BackgroundAbnormal junctions and permeability of myelin in PMP22‐deficient nerves
Guo, J., Wang, L., Zhang, Y., Wu, J., Arpag, S., Hu, B., Imhof, B. A., Tian, X., Carter, B. D., Suter, U., et al. (2013) · Annals of Neurology · doi:10.1002/ana.24086 · Cited by 69
“Although the loss of myelin is widely regarded as one of the most important mechanisms that alter nerve conduction, effective nerve conduction is also thought to require a proper myelin seal through myelin junctions (such as tight junctions, adherens junctions).(2) These junctions seal the spaces between adjacent myel…”
BackgroundSubtle Paranodal Injury Slows Impulse Conduction in a Mathematical Model of Myelinated Axons
Babbs, C. F., & Shi, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067767 · Cited by 68
“The simple computational model of myelinated nerve conduction presented here provides several insights into the normal functioning and the failure of myelinated axons, which remain points of discussion in the 21 century [35,36].”
BackgroundConduction Block in PMP22 Deficiency
Bai, Y., Zhang, X., Katona, I., Saporta, M., Shy, M. E., O’Malley, H. A., Isom, L. L., Suter, U., & Li, J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4264-09.2010 · Cited by 68
“Reduced axonal diameter rapidly raises axial resistance to action potential propagation since axial electric resistance of axons is inversely proportion to the square of axonal diameter (Hartline and Colman, 2007).”
BackgroundDynamic tractography: Integrating cortico-cortical evoked potentials and diffusion imaging
Silverstein, B. H., Asano, E., Sugiura, A., Sonoda, M., Lee, M., & Jeong, J. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116763 · Cited by 67
Evolution of rapid nerve conduction
Castelfranco, A. M., & Hartline, D. K. (2016) · Brain Research · doi:10.1016/j.brainres.2016.02.015 · Cited by 69
Self-citationGonzález‐Pérez, A., Budvytytė, R., Mosgaard, L. D., Nissen, S., & Heimburg, T. (2014) · Physical Review X · doi:10.1103/physrevx.4.031047 · Cited by 66
“The giant axons of the ventral cord of lobster are considered non-myelinated [29].”
BackgroundChen, H., Garcia‐Gonzalez, D., & Jérusalem, A. (2019) · Physical review. E · doi:10.1103/physreve.99.032406 · Cited by 68
Myelin copper and the cuprizone model of schizophrenia
Konradi, C. L. (2010) · Frontiers in Bioscience-Scholar · doi:10.2741/s129 · Cited by 68
“All myelin, regardless of species, provides multilamellar membrane wrapping and promotes 'saltatory' conductance (24, 25).”
BackgroundIs activity regulation of late myelination a plastic mechanism in the human nervous system?
Ullén, F. (2009) · Neuron Glia Biology · doi:10.1017/s1740925x09990330 · Cited by 70
Metadata
- Authors
- Hartline, D. K., & Colman, D. R.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- Montreal Neurological Institute and Hospital (CA)
- Corresponding author
- Hartline, D.K.
- ORCID
- Colman, D.R.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 17
- Issue
- 1
- Pages
- R29-R35
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2129836920
- Cited by
- 478
- References
- 42
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 25 · 2023: 22 · 2022: 24 · 2021: 35 · 2020: 28 · 2019: 38 · 2018: 21 · 2017: 32 · 2016: 37 · 2015: 22 · 2014: 25 · 2013: 33 · 2012: 21
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- myelination, myelinated axons, saltatory conduction, squid giant axon, nodal regions, invertebrate nervous system, vertebrate nervous system, Annelida, Crustacea
- MeSH terms
- Action Potentials, Animals, Axons, Cell Adhesion, Biological Evolution, Nerve Fibers, Myelinated, Neural Conduction
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