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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Within the peripheral nervous system, different nerve fibers conduct action potentials at different speeds and with variable frequency and duration, which can affect their tolerance to electrical stimulation regimes.
“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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“…is key for saltatory propagation, the process by which action potentials are regenerated from node to node, effectively speeding up impulse propagation (Bhatt, Fan, & Pang, 2014; Frankenhaeuser, 1952; Hartline & Colman, 2007; McDougall, Vargas Riad, Silva‐Gotay, Tavares, & Harpalani, 2018).”
BackgroundTight junctions potentiate the insulative properties of small CNS myelinated axons
Devaux, J. J., & Gow, A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200808034 · Cited by 108 · see citing works
“…for D ow nloaded from http://rupress.org/jcb/article-pdf/183/5/909/1341104/jcb_200808034.pdf by Bibliotheque U niversitaire user on 01 June 2021 919TIGHT JUNCTION FUNCTION IN CNS MYELIN • Devaux and Gow internode length, and myelin thickness ( g ratio; for review see Hildebrand and Mohseni, 2005 ).”
Marion, C. M., Radomski, K. L., Cramer, N., Galdzicki, Z., & Armstrong, R. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0819-18.2018 · Cited by 87 · see citing works
“Myelin sheaths enwrap axons to enable rapid impulse firing and a tenfold increase of action potential conduction velocity (Hartline and Colman, 2007).”
BackgroundAxon-glia interaction and membrane traffic in myelin formation
White, R., & Krämer‐Albers, E. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00284 · Cited by 101 · see citing works
“Although myelin seems to have arisen independently several times in evolution and is found in vertebrate and invertebrate species, it shares remarkable morphological similarities (Hartline and Colman, 2007).”
BackgroundLopez‐Verrilli, M. A., & Court, F. A. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00205 · Cited by 100 · see citing works
“It is well known that the myelin sheath, by increasing the operational resistance of the axolemma, greatly increases the velocity of the nerve impulse, which is a passive effect (Hartline and Colman, 2007).”
BackgroundThompson, A., Murphy, D., Dell’Acqua, F., Ecker, C., McAlonan, G. M., Howells, H., Baron‐Cohen, S., Lai, M., & Lombardo, M. V. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.06.020 · Cited by 94 · see citing works
“These differences in diffusion measurements have previously been associated with alterations to tract structure, such as reduced tract coherence and organization, and reduced myelination (37) and may be associated with reduced conduction speed (38).”
Glia unglued: How signals from the extracellular matrix regulate the development of myelinating glia
Colognato, H., & Tzvetanova, I. D. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20966 · Cited by 90 · see citing works
Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system
Ohno, M., Hiraoka, Y., Matsuoka, T., Tomimoto, H., Takao, K., Miyakawa, T., Oshima, N., Kiyonari, H., Kimura, T., Kita, T., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2438 · Cited by 93 · see citing works
“Because axonal conduction is determined by axon caliber and myelin sheath thickness, axonal maturation (radial growth of axon) and myelination are essential processes for establishing an efficient neuronal signaling networ”
BackgroundHartline, D. K. (2008) · Neuron Glia Biology · doi:10.1017/s1740925x09990263 · Cited by 91 · see citing works
Self-citationZada, D., Tovin, A., Lerer-Goldshtein, T., Vatine, G. D., & Appelbaum, L. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004615 · Cited by 92 · see citing works
“Loss of myelin sheaths produces a wide variety of neurological symptoms, including the slow progression of action potential and deficient axon elaboration [79].”
BackgroundBad wrap: Myelin and myelin plasticity in health and disease
Gibson, E. M., Geraghty, A. C., & Monje, M. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22541 · Cited by 87 · see citing works
Ensheathment and Myelination of Axons: Evolution of Glial Functions
Nave, K., & Werner, H. B. (2021) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-100120-122621 · Cited by 89 · see citing works
Chamberlain, K. A., Nanescu, S. E., Psachoulia, K., & Huang, J. K. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.10.010 · Cited by 88 · see citing works
“This exquisite organization defines the typical vertebrate nerve fiber and is crucial for saltatory propagation of electrical impulses down the axon, enabling rapid communication between networks of nerve cells in the CNS (Bhatt et al., 2014; Frankenhaeuser, 1952; Hartline and Colman, 2007).”
BackgroundSystematic Review of Pharmacological Properties of the Oligodendrocyte Lineage
Marinelli, C., Bertalot, T., Zusso, M., Skaper, S. D., & Giusti, P. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00027 · Cited by 87 · see citing works
“A lipid-rich membrane, myelin (Virchow, 1854), insulates the axon and allows for rapid conduction of such impulses and proper delivery to the target cell (Hartline and Colman, 2007).”
BackgroundElectron microscopy of myelin: Structure preservation by high-pressure freezing
Möbius, W., Nave, K., & Werner, H. B. (2016) · Brain Research · doi:10.1016/j.brainres.2016.02.027 · Cited by 86 · see citing works
“Yet, a structural equivalent of vertebrate myelin has been observed in some invertebrate species [68] (Wilson & Hartline, in revision).”
Influence of Mechanical Stimuli on Schwann Cell Biology
Belin, S., Zuloaga, K. L., & Poitelon, Y. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00347 · Cited by 88 · see citing works
“…vertebrates by allowing a faster and efficient conduction of nerves action potentials (Morell and Quarles, 1999), thus enabling faster predatory and escape maneuvers and the development of large and complex nervous systems (Zalc and Colman, 2000; Hartline and Colman, 2007; Zalc et al., 2008).”
BackgroundProteome profile of peripheral myelin in healthy mice and in a neuropathy model
Siems, S. B., Jahn, O., Eichel‐Vogel, M. A., Kannaiyan, N. R., Wu, L. M. N., Sherman, D. L., Kusch, K., Hesse, D., Jung, R. B., Fledrich, R., et al. (2020) · eLife · doi:10.7554/elife.51406 · Cited by 85 · see citing works
“for normal motor and sensory capabilities of vertebrates (1,2).”
BackgroundMarion, C. M., McDaniel, D. P., & Armstrong, R. C. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.113040 · Cited by 81 · see citing works
“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 84 · see citing works
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 84 · see citing works
“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. D., & Lee, H. K. (2022) · Glia · doi:10.1002/glia.24238 · Cited by 71 · see citing works
“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 81 · see citing works
“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 77 · see citing works
“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 65 · see citing works
“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 78 · see citing works
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 75 · see citing works
“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 74 · see citing works
“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 · see citing works
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 · see citing works
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 74 · see citing works
“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 74 · see citing works
Kucenas, S., Snell, H. D., & Appel, B. (2008) · Neuron Glia Biology · doi:10.1017/s1740925x09990123 · Cited by 73 · see citing works
“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 · see citing works
“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 72 · see citing works
“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 71 · see citing works
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 70 · see citing works
“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 70 · see citing works
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 70 · see citing works
Foster, A. Y., Bujalka, H., & Emery, B. (2019) · Glia · doi:10.1002/glia.23629 · Cited by 65 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
Evolution of rapid nerve conduction
Castelfranco, A. M., & Hartline, D. K. (2016) · Brain Research · doi:10.1016/j.brainres.2016.02.015 · Cited by 64 · see citing works
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 · see citing works
“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 66 · see citing works
Myelin copper and the cuprizone model of schizophrenia
Konradi, C. (2010) · Frontiers in Bioscience-Scholar · doi:10.2741/s129 · Cited by 67 · see citing works
“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 66 · see citing works
- 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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