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Irregular geometries in normal unmyelinated axons: A 3D serial EM analysis

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Journal of Neurocytology

Summary

Axons have generally been represented as straight cylinders. It is not at all uncommon for anatomists to take single cross-sections of an axonal bundle, and from the axonal diameter compute expected conduction velocities. This assumes that each cross-section represents a slice through a perfect cylinder. We have examined the three-dimensional geometry of 98 central and peripheral unmyelinated axons, using computer-assisted serial electron microscopy. These reconstructions reveal that virtually all unmyelinated axons have highly irregular axial shapes consisting of periodic varicosities. The varicosities were, without exception, filled with membranous organelles frequently including mitochondria, and have obligatory volumes similar to that described in other neurites. The mitochondria make contact with microtubules, while the other membraneous organelles were frequently found free floating in the cytoplasm. We conclude that unmyelinated axons are fundamentally varicose structures created by the presence of organelles, and that an axon's calibre is dynamic in both space and time.

These irregular axonal geometries raise serious doubts about standard two dimensional morphometric analysis and suggest that electrical properties may be more heterogeneous than expected from single section data. These results also suggest that the total number of microtubules contained in an axon, rather than its single section diameter, may prove to be a more accurate predictor of properties such as conduction velocity. Finally, these results offer an explanation for a number of pathological changes that have been described in unmyelinated axons.

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References

  • Aguayo, A. J., Bray, G. M., Terry, L. C. &Sweezey, E. (1976) Three dimensional analysis of unmyelinated fibers in normal and pathologic autonomic nerves.Journal of Neuropathology and Experimental Neurology 35, 136–51.

    PubMed  Google Scholar 

  • Allen, R. D., Weiss, D. G., Hayden, J. H., Brown, D. T., Fujiwake, H. &Simpson, M. (1985) Gliding movement and bidirectional transport along single native micro- tubules from squid axoplasm: evidence for an active role of microtubules in cytoplasmic transport.Journal of Cell Biology 100, 1736–52.

    PubMed  Google Scholar 

  • Basbaum, C. B. &Heuser, J. E. (1979) Morphological studies of stimulated adrenergic axon varicosities in the mouse vas deferens.Journal of Cell Biology 80, 310–25.

    PubMed  Google Scholar 

  • Berthold, C.-H. (1978) Morphology of normal peripheral axons. In:Physiology and Pathobiology of Axons (edited byWaxman, S. G.) New York: Raven Press.

    Google Scholar 

  • Black, S. E. (1981) Pseudopods and synapses: the amoeboid theories of neuronal mobility and the early formulation of the synapse concept, 1894–1900. The Osler Medical Essay.Bulletin of the History of Medicine 55, 34–58.

    PubMed  Google Scholar 

  • Buckley, K. M. &Landis, S. C. (1983) Morphological studies of synapses and varicosities in dissociated cell cultures of sympathetic neurons.Journal of Neurocytology 12, 67–92.

    PubMed  Google Scholar 

  • Carpenter, M. B. &Sutin, J. (1983)Human Neuroanatomy. Baltimore: Williams and Wilkins.

    Google Scholar 

  • Cheng, T. P. &Reese, T. S. (1988) Compartmentalization of anterogradely and retrogradely transported organelles in axons and growth cones from chick optic tectum.Journal of Neuroscience 8, 3190–9.

    PubMed  Google Scholar 

  • Chou, S. M. &Hartmann, H. A. (1964) Axonal lesions and waltzing syndrome after IDPN administration in rats. With a concept- ‘axostasis’.Acta Neuropathologica 3, 428–50.

    Google Scholar 

  • Clark, A. W., Parhad, I. M., Griffin, J. W. &Price, D. L. (1984) Neurofilamentous axonal swellings as a normal finding in spinal anterior horn of man and other primates.Journal of Neuropathology and Experimental Neurology 43, 253–62.

    PubMed  Google Scholar 

  • Coers, C. &Woolf, A. L. (1959)The Innervation of Muscle. Oxford: Oxford University Press.

    Google Scholar 

  • Cottrell, D. F. &Hunter, J. M. (1984) Scaling factor relating conduction velocity and transverse axon profile for nonmyelinated alimentary nerves.Experimental Neurology 90, 700–2.

    Google Scholar 

  • Ellias, S. A. &Stevens, J. K. (1980) The dendritic varicosity: a mechanism for electrically isolating the dendrites of cat retinal amacrine cells?Brain Research 196, 365–72.

    PubMed  Google Scholar 

  • Ellias, S., Greenberg, M. &Stevens, J. K. (1985) Active and passive propagation in inhomogeneous axons: theoretical and serial EM studies of varicose unmyelinated nerves.Society for Neuroscience Abstracts

  • Famiglietti, E. V. (1985) Starburst amacrine cells: morphological constancy and systematic variation in the anisotropic field of rabbit retinal neuronsJournal of Neuroscience 5, 562–77.

    PubMed  Google Scholar 

  • Forman, D. S., Lynch, K. J. &Smith, R. S. (1987) Organelle dynamics in lobster axons: anterograde, retrograde and stationary mitochondria.Brain Research 412, 96–106.

    PubMed  Google Scholar 

  • Fukada, Y., Hsiao, C. F., Watanabe, M. &Ito, H. (1984) Morphological correlates of physiologically identified Y-, X-, and W-cells in cat retina.Journal of Neurophysiology 52, 999–1013.

    PubMed  Google Scholar 

  • Gallego, R. &Belmonte, C. (1984) Axonal conduction velocity and input conductance in petrosal ganglion primary sensory neurons of the cat.Neuroscience Letters 52, 117–22.

    PubMed  Google Scholar 

  • Gasser, H. S. (1950) Unmedullated fibers originating in dorsal root ganglia.Journal of General Physiology 33, 651–90.

    PubMed  Google Scholar 

  • Gasser, H. S. (1955) Properties of dorsal root unmedullated fibers on the two sides of the ganglionJournal of General Physiology 38, 709–28.

    PubMed  Google Scholar 

  • Greenberg, M. M. &Stevens, J. K. (1986) Organelles organize microtubules into transient baskets: a serial EM 3D reconstruction of systems of axonal microtubules.Society for Neuroscience Abstracts 12, 000–000.

    Google Scholar 

  • Griffin, J. W., Price, D. L., Engel, W. K. &Drachman, D. B. (1977) The pathogenesis of reactive axonal swellings: role of axonal transport.Journal of Neuropathology and Experimental Neurology 36, 214–27.

    PubMed  Google Scholar 

  • Hsiao, C. F., Watanabe, M. &Fukada, Y. (1984) The relation between axon diameter and axonal conduction velocity of Y, X, and W cells in the cat retina.Brain Research 309, 357–61.

    PubMed  Google Scholar 

  • Jacobs, J. R. &Stevens, J. K. (1986a) Changes in the organization of the neuritic cytoskeleton during nerve growth factor-activated differentiation of PC12 cells: a serial electron microscopic study of the development and control of neurite shape.Journal of Cell Biology 103, 895–906.

    PubMed  Google Scholar 

  • Jacobs, J. R. &Stevens, J. K. (1986b) Experimental modification of PC12 neurite shape with the microtubule-depolymerizing drug Nocodazole: a serial electron microscopic study of neurite shape control.Journal of Cell Biology 103, 907–15.

    PubMed  Google Scholar 

  • Jacobs, R. &Stevens, J. (1987) Dynamics of behavior during neuronal morphogenesis in culture.Cell Motility and the Cytoskeleton 8, 250–60.

    PubMed  Google Scholar 

  • Jellinger, K. &Jirasek, A. (1971) Neuroaxonal dystrophy in man: character and natural history.Acta neuropathologica Suppl V: 3–16.

    Google Scholar 

  • Jonakait, G. M., Gintzler, A. R. &Gershon, M. D. (1979) Isolation of axonal varicosities (autonomie synaptosomes) from the enteric nervous system.Journal of Neurochemistry 32, 1387–1400.

    Google Scholar 

  • Koenig, H. (1969) Acute axonal dystrophy caused by fluorocitrate: the role of mitochondrial swelling.Science 164, 310–12.

    PubMed  Google Scholar 

  • Koenig, E., Kinsman, S., Repasky, E. &Sultz, L. (1985) Rapid mobility of motile varicosities and inclusions containing a-spectrin, actin, and calmodulin in regenerating axons in vitro.Journal of Neuroscience 5, 715–29.

    Google Scholar 

  • Lasek, R. J. &Brady, S. T. (1983) Orthograde and retrograde particle movement in isolated axoplasm from the giant axon of the squid.Journal of Cell Biology 97, A4.

    Google Scholar 

  • Leitao, C., Stevens, J. &Dekel, D. (1988) A rapid automatic algorithm for placing smooth three dimensional surfaces on complex contoured, biological objects. U.S. Patent application 1988.

  • Leonhardt, H. (1976) ‘Axonal spheroids’ in the spinal cord of normal rabbits.Cell & Tissue Research 174, 99–108.

    Google Scholar 

  • Martz, D., Lasek, R. J., Brady, S. T. &Allen, R. D. (1984) Mitochondrial motility in axons: membranous organelles may interact with the force generating system through multiple surface binding sites.Cell Motility 4, 77–154.

    PubMed  Google Scholar 

  • McGuire, B. A., Stevens, J. K. &Sterling, P. (1986) Microcircuitry of Beta ganglion cells in cat retina.Journal of Neuroscience 6, 907–18.

    Google Scholar 

  • Morris, J. H., Hudson, A. R. &Weddell, G. (1972) A Study of degeneration and regeneration in the divided rat sciatic nerve based on electron microscopy. III. Changes in the axons of the proximal stump.Zeitschrift für Zellforschung 124, 131–64.

    Google Scholar 

  • Ochs, S. &Jersild, J. (1987) Cytoskeletal organelles and myelin structure of beaded nerve fibers.Neuroscience 22, 1041–56.

    PubMed  Google Scholar 

  • Paintal, A. S. (1966) The influence of diameter of medullated nerve fibres of cats on the rising and falling phases of the spike and its recovery.Journal of Physiology 184, 791–811.

    PubMed  Google Scholar 

  • Paintal, A. S. (1967) A comparison of the nerve impulses of mammalian non-medullated nerve fibres with those of the smallest diameter medullated fibres.Journal of Physiology 193, 523–33.

    Google Scholar 

  • Sanchez, R. M. &Dunkelberger, G. R., Quigley, H. A. (1986) The number and diameter distribution of axons in the monkey optic nerve.Investigative Ophthalmology and Visual Science 27, 1342–50.

    PubMed  Google Scholar 

  • Sasaki, S. Stevens, J. K. &Bodick, N. (1983) Serial reconstruction of microtubular arrays in dendrites: the cytoskeleton of the vertebrate dendrite.Brain Research 259, 193–206.

    PubMed  Google Scholar 

  • Sasaki-Sherrington, S. E., Jacobs, J. R. &Stevens, J. K. (1984) Intracellular control of axial shape in non-uniform neurites: a serial electron microscopic analysis of organelles and microtubules in AI and AII retinal amacrine neurites.Journal of Cell Biology 98, 1279–90.

    PubMed  Google Scholar 

  • Scwab, B. W., Arezzo, J. C., Paldino, A. M., Flohe, L., Matthiesson, T. &Spencer, P. S. (1984) Rabbit sural nerve responses to chronic treatment with thalidomide and supidimide.Muscle & Nerve 7, 362–8.

    Google Scholar 

  • Seitelberger, F. (1971) Neuropathological conditions related to neuroaxonal dystrophy.Acta Neuropathologica Suppl V, 17–29.

    Google Scholar 

  • Smith, D. O. &Rosenheimer, J. L. (1984) Factors governing speed of action potential conduction and neuromuscular transmission in aged rats.Experimental Neurology 83, 358–66.

    PubMed  Google Scholar 

  • Stein, R. B. &Pearson, K. G. (1971) Predicted amplitude and form of action potentials recorded from unmyelinated nerve fibres.Journal of Theoretical Biology 32, 539–58.

    PubMed  Google Scholar 

  • Stevens, J. K. &Trogadis, J. (1984) Computer-assisted reconstruction from serial electron micrographs: a tool for the systematic, study of neuronal form and function.Advances in Cellular Neurobiology 5, 341–69.

    Google Scholar 

  • Stevens, J. K., Trogadis, J. &Jacobs, R. (1988) Development and control of axial neurite form: A serial electron microscopic analysis. InIntrinsic Determinants of Neuronal Form and Function (edited byLasek, R. &Black, M.) pp. 115–45, New York: Alan R. Liss.

    Google Scholar 

  • Suzuki, K. &Zagoren, J. C. (1975) Focal axonal swelling in cerebellum of Quaking mouse: light and electron microscopic studies.Brain Research 85, 38–43.

    PubMed  Google Scholar 

  • Thureson-Klein, A., Klein, R. L. &Johannsson, O. (1979) Catecholamine-rich cells and varicosities in bovine splenic nerve, vesicle contents and evidence for exocytosis.Journal of Neurobiology 10, 309–24.

    PubMed  Google Scholar 

  • Vale, R. D., Schnapp, B. J., Reese, T. S. &Sheetz, M. P. (1985) Movement of organelles along filaments dissociated from the axoplasm of the squid giant axon.Cell 40, 449–54.

    PubMed  Google Scholar 

  • Woodbury, P. B. &Ulinski, P. S. (1986) Conduction velocity, size and distribution of optic nerve axons in the turtle,Pseudemys scripta elegans.Anatomy of Embryology 174, 253–63.

    Google Scholar 

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Authors and Affiliations

  1. Playfair Neuroscience Unit, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, M5T 2S8, Toronto, Ontario, Canada

    M. M. Greenberg, C. Leitao, J. Trogadis & J. K. Stevens

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  1. M. M. Greenberg
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  2. C. Leitao
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  3. J. Trogadis
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  4. J. K. Stevens
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Greenberg, M.M., Leitao, C., Trogadis, J. et al. Irregular geometries in normal unmyelinated axons: A 3D serial EM analysis. J Neurocytol 19, 978–988 (1990). https://doi.org/10.1007/BF01186825

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  • DOI: https://doi.org/10.1007/BF01186825

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