Skip to main content
SpringerLink
Log in

Chemoattraction of sensory neuron growth cones by diffusible concentration gradients of acetylcholine

  • Part IX Trophic Factors' Importance for Neurodegenerative Disorders
  • Published:
Molecular and chemical neuropathology

Abstract

Axon guidance cues are critical for the development and repair of both the central and peripheral nervous systems. These cues serve to help select the pathways taken by axon growth cones, by attracting or repulsing them. During development and following injury to the adult peripheral nervous system, neurons must extend processes, often over long distances, through a variety of cellular environments composed of innervated and uninnervated cells, to find, recognize, and synapse on their appropriate targets. The responsibility for recognizing and responding to the extensive number of cues that are encountered as axons alongate falls on the growth cones at the tip of the elongating axons. Cajal (1928) proposed that denervated target cells release diffusible factors that assist in orienting the direction of outgrowth of peripheral axons. However, it is only relatively recently that experiments to identify the molecules responsible for serving this function, and the molecular mechanisms by which they function, have begun to bear fruit. Gradients of both substrate-bound and diffusible factors have now been shown to play critical roles in directing axon outgrowth. The present experiments were aimed at determining whether the neurotransmitter acetylcholine (ACh) can act as a chemoattractant for adult sensory neuron growth cones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aaronson O. S., Golding J. P., and Tonge D. A. (1995) Oriented growth of regenerating axons in axolotl forelimbs is consistent with guidance by diffusible factors from distal nerve stumps.Neuroscience 66, 201–213.

    Article  CAS  Google Scholar 

  • Ambrose W. W. and McNeill M. E. (1978) Graphic presentation of the distribution of acetylcholinesterase in cat dorsal root ganglion neurons.Histochem. J. 10, 771–720.

    Article  CAS  Google Scholar 

  • Baier H. and Bonhoeffer F. (1992) Axon guidance by gradients of a target-derived component.Science 255, 472–475, 1992.

    Article  CAS  Google Scholar 

  • Bonhoeffer F. and Huf J. (1982)In vitro experiments in axon guidance demonstrating an anterior-posterior gradient on the tectum.EMBO J. 1, 427–431.

    Article  CAS  Google Scholar 

  • Cajal S. R. Y. (1928)Degeneration and regeneration of the nervous system. (May R. M. trans.) Oxford University Press, London.

    Google Scholar 

  • Colamarino S. A. and Tessier-Lavigne M. (1995) The axonal chemoattractant netrin-1 is also a chemorepellant for trochlear motor axons.Cell 8, 621–629.

    Article  Google Scholar 

  • Dan Y. and Poo M.-M. (1992) Quantal transmitter secretion from myocytes loaded with acetylcholine.Nature 259, 733–736.

    Article  Google Scholar 

  • Davies A. M., Bantlow C., Heumann R., Korschung S., Rohrer H., and Thoenen H. (1987) Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor.Nature 326, 353–363.

    Article  CAS  Google Scholar 

  • Dobretsov M., Dobretsov A., and Kuffler D. P. (1994) Influence of factors released from sciatic nerve on adult dorsal root ganglion neurons.J. Neurobiol. 25, 1249–1266.

    Article  CAS  Google Scholar 

  • Gundersen R. W. and Barrett J. N. (1979) Neuronal chemotaxis: chick dorsal root axons turn towards high concentrations of nerve growth factor.Science 206, 1079–1080.

    Article  CAS  Google Scholar 

  • Haydon P. G., McCobb D. P., and Kater S. B. (1984) Serotonin selectively inhibits growth cone dynamics and synaptogenesis of specific identified neurons ofHelisoma.Science 226, 561–564.

    Article  CAS  Google Scholar 

  • Heffner C. D., Lumsden A. G. S., and O'Leary D. D. M. (1990) Target control of collateral extension and directional axon growth in the mammalian brain.Science 247, 217–220.

    Article  CAS  Google Scholar 

  • Heumann R., Lindholm D., Brandtlow C., Meyer M., Radeke M. J., Misko Y., Shooter E., and Thoenen H. (1987) Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration and regeneration: role of macrophages.Proc. Natl. Acad. Sci. USA 84, 8735–8739.

    Article  CAS  Google Scholar 

  • Hume R. I., Role L. R., and Fischbach G. D. (1983) Acetylcholine release from growth cones detected with patches of acetylcholine receptor-rich membrane.Nature 305, 632–634.

    Article  CAS  Google Scholar 

  • Kalina M. and Wolman M. (1978) Correlative histochemical and morphological study on the maturation of sensory ganglion cells in the rat.Histochemie 22, 100–108.

    Article  Google Scholar 

  • Kennedy T. E., Serafini T., de la Torre J. R., and Tessier-Lavigne M. (1994) Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord.Cell 78, 425–436.

    Article  CAS  Google Scholar 

  • Kolodkin A. L., Matthes D. J., O'Connor T. P., Patel N. H., Admon A., Bentley D., and Goodman C. S., 1992) Fasciclin IV: sequence, expression, and function during growth cone guidance in the grasshopper embryo.Neuron 9, 831–845.

    Article  CAS  Google Scholar 

  • Kolodkin A. L., Matthes D. J., and Goodman C. S. (1993) The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules.Cell 75, 1389–1399.

    Article  CAS  Google Scholar 

  • Kuffler D. P. (1989) Regeneration of muscle axons in the frog is directed by diffusible factors from denervated muscle and nerve tubes.J. Comp. Neurol. 281, 416–425.

    Article  CAS  Google Scholar 

  • Kuffler D. P. (1994) Growth cones are directed up concentration gradients by factors released from denervated peripheral nerve tubes.Soc. Neurosci. Abstr. 284, 2.

    Google Scholar 

  • Kuffler D. P. and Luethi T. (1993) Identification of molecules in a muscle extracellular matrix extract that promotes process outgrowth from cultured adult frog motoneurons.J. Neurobiol. 24, 515–527.

    Article  CAS  Google Scholar 

  • Kuffler D. P. and Megwinoff O. (1994) Neurotrophic influence of denervated sciatic nerve on adult dorsal root ganglion neurons.J. Neurobiol. 25, 1267–1282.

    Article  CAS  Google Scholar 

  • Lipton S. A., Frosch M. P., Phillips M. D., Tauck D. L., and Aizenman E. (1988) Nicotinic antagonists enhance process outgrowth by rat retinal ganglion cells in culture.Science 239, 1293–1296.

    Article  CAS  Google Scholar 

  • Lumsden A. G. S. and Davies A. W. (1983) Earliest sensory nerve fibers are guided to peripheral targets by attractants other than nerve growth factor.Nature 306, 786–788.

    Article  CAS  Google Scholar 

  • Lumsden A. G. S. and Davies A. W. (1986) Chemotropic effect of specific target epithelium in the developing mammalian nervous system.Nature 323, 538–539.

    Article  CAS  Google Scholar 

  • Luo Y., Raible D., and Raper J. A. (1993) Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones.Cell 75, 217–227.

    Article  CAS  Google Scholar 

  • Matthes D., Sink H., Kolodkin A. L. and Goodman C. S. (1995) Semaphorin II can function as a selective inhibitor of specific synaptic arborization.Cell 81, 631–639.

    Article  CAS  Google Scholar 

  • Mattson M. P., Dou P., and Kater S. B. (1988) Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons.J. Neurosci. 8, 2087–2100.

    Article  CAS  Google Scholar 

  • Messersmith E. K., Leonardo E. D., Shatz C. J., Tessier-Lavigne M., Goodman C. S., and Kolodkin A. L. (1995) Semaphorin III can function as a selective chemorepellant to pattern sensory projections in the spinal cord.Neuron,14: 949–959.

    Article  CAS  Google Scholar 

  • Placzek M., Tessier-Lavigne M., Jessell T. M., and Dodd J. (1990) Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant.Development 110, 1930–1942.

    Google Scholar 

  • Politis M. J., Ederle K., and Spencer P. S. (1982) Tropism in nerve regenerationin vitro. Attraction of regenerating axons by diffusible factors derived from cells in distal nerve stumps of transected peripheral nerves.Brain Res. 253, 1–12.

    Article  CAS  Google Scholar 

  • Richardson P. M. and Ebendal T. (1982) Nerve growth factor activities in rat peripheral nerve.Brain Res. 246, 57–64.

    Article  CAS  Google Scholar 

  • Salonen V., Peltonen J., Roytta R., and Virtanen I. (1987) Laminin in traumatized peripheral nerve: basement membrane changes during degeneration and regeneration.J. Neurocytol. 16, 713–720.

    Article  CAS  Google Scholar 

  • Sato M., Lopez-Mascaraque L., Heffner C. D., and O'Leary D. D. M. (1994) Action of a diffusible target-derived chemoattractant on central axon branch induction and directed growth.Neuron 13, 791–803.

    Article  CAS  Google Scholar 

  • Scott S. A. (1992)Sensory Neurons: Diversity, Development, and Plasticity, Oxford University Press, New York.

    Google Scholar 

  • Serafini T., Kennedy T. E., Galko M. J., Mirzyab C., Jessell T. M., and Tessier-Lavigne, M. (1994) The netrins define a family of axon outgrowth-promoting proteins homologous toC. elegans UNC-6.Cell 78, 409–424.

    Article  CAS  Google Scholar 

  • Skene J. H. P. and Shooter E. M. (1983) Denervated sheath cells secrete a new protein after nerve injury.Proc. Natl. Acad. Sci. USA 80, 4169–4173.

    Article  CAS  Google Scholar 

  • Snow D. M. and Letourneau P. C. (1992) Neurite outgrowth on a step gradient of chondroitin surface proteoglycan (CS-PG).J. Neurobiol. 23, 322–336.

    Article  CAS  Google Scholar 

  • Stahl B., Müller B., von Boxberg Y., Cox E. C., and Bonhoeffer F. (1990) Biochemical characterization of a putative guidance molecule in the chick visual system.Neuron 5, 734–743.

    Article  Google Scholar 

  • Stahl B., Boxberg Y., Müller B., Walter J., Schwartz U., and Bonhoeffer F. (1991) Directional cues for retinal axons.Cold Spring Harb. Symp. Quant. Biol. 55, 351–357.

    Article  Google Scholar 

  • Tessier-Lavigne M., Placzek M., Lumsden A. G. S., Dodd J., and Jessell T. M. (1988) Chemotropic guidance of developing axons in the mammalian nervous system.Nature 336, 775–777.

    Article  CAS  Google Scholar 

  • Xie Z.-P. and Poo M.-M. (1986) Initial events in the formation of neuromuscular synapses: rapid induction of acetylcholine release from embryonic neuron.Proc. Natl. Acad. Sci. USA 83, 7069–7073.

    Article  CAS  Google Scholar 

  • Zheng J. Q., Felder M., Connor J. A., and Poo M.-M. (1994) Turning of nerve growth cones induced by neurotransmitters.Nature 368, 140–144.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Neurobiology and Dept. of Physiology, Medical Sciences Campus, University of Puerto Rico, 00901, San Juan, PR

    Damien P. Kuffler

Authors
  1. Damien P. Kuffler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuffler, D.P. Chemoattraction of sensory neuron growth cones by diffusible concentration gradients of acetylcholine. Molecular and Chemical Neuropathology 28, 199–208 (1996). https://doi.org/10.1007/BF02815223

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02815223

Index Entries

Search

Navigation