Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Motor coordination without action potentials in the mammalian spinal cord

Abstract

Coordination of neuronal activity to produce movement is generally thought to depend on spike activity in premotor interneuronal networks. Here we show that even without such activity, the neonatal rat spinal cord could produce a stable motor rhythm mediated by the synchronization of motor neuron oscillations across gap junctions. These rhythms, however, were not coordinated between motor pools in different parts of the spinal cord. We further showed that neural coordination through gap junctions contributed to the fundamental organization and function of spinal motor systems. These results suggest that neural coordination across gap junctions is important in motor-pattern generation in the mammalian spinal cord.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Rhythmic motor patterning without action potential-dependent chemical synapses.
Figure 2: Coordinated motor rhythms after action potential blockade by TTX.
Figure 3: Interactions between intrinsic oscillations and coordinated network activity in the presence of TTX.
Figure 4: Network coordination in the absence of action potentials is mediated by gap junctions.
Figure 5: TTX-resistant motor rhythm requires NMDA-dependent intrinsic oscillations.
Figure 6: Ventral root oscillations produced in different segments and effects of gap junction blockade on normal locomotion.

Similar content being viewed by others

References

  1. Bernstein, N. The Coordination and Regulation of Movements (Pergamon, New York, 1967).

    Google Scholar 

  2. Kudo, N. & Yamada, T. N-methyl-d,l-aspartate-induced locomotor activity in a spinal cord-hindlimb muscles preparation of the newborn rat studied in vitro. Neurosci. Lett. 75, 43–48 (1987).

    Article  CAS  Google Scholar 

  3. Smith, J. C., Feldman, J. L. & Schmidt, B. J. Neural mechanisms generating locomotion studied in mammalian brain stem-spinal cord in vitro. FASEB 2, 2283–2288 (1988).

    Article  CAS  Google Scholar 

  4. Cazalets, J. R., Sqalli-Houssaini, Y. & Clarac, F. Activation of the central pattern generators for locomotion by serotonin and excitatory amino acids in neonatal rat. J. Physiol. (Lond.) 455, 187–204 (1992).

    Article  CAS  Google Scholar 

  5. Cowley, K. C. & Schmidt, B. J. A comparison of motor patterns induced by N-methyl-d-aspartate, acetylcholine and serotonin in the in vitro neonatal rat spinal cord. Neurosci. Lett. 171, 147–150 (1994).

    Article  CAS  Google Scholar 

  6. Kiehn, O. & Kjaerulff, O. Spatiotemporal characteristics of 5–HT and dopamine-induced rhythmic hindlimb activity in the in vitro neonatal rat. J. Neurophysiol. 75, 1472–1482 (1996).

    Article  CAS  Google Scholar 

  7. Kudo, N. & Yamada, Y. Morphological and physiological studies of development of the monosynaptic reflex pathway in the rat lumbar spinal cord. J. Physiol. 389, 441–459 (1987).

    Article  CAS  Google Scholar 

  8. Johnson, S. M., Smith, J. C., Funk, G. D. & Feldman, J. L. Pacemaker behavior of respiratory neurons in medullary slices from neonatal rat. J. Neurophysiol. 72, 2598–2608 (1994).

    Article  CAS  Google Scholar 

  9. Hille, B. Ionic Channels of Excitable Membranes (Sinauer, Sunderland, Massachusetts, 1992).

    Google Scholar 

  10. Hochman, S., Jordan, L. M. & MacDonald, J. F. N-methyl-d-aspartate receptor-mediated voltage oscillations in neurons surrounding the central canal in slices of rat spinal cord. J. Neurophysiol. 72, 565–577 (1994).

    Article  CAS  Google Scholar 

  11. Raastad, M, Enriquez-Denton, M & Kiehn, O. Synaptic signaling in an active central network only moderately changes passive membrane properties. Proc. Natl. Acad. Sci. USA 95, 10251–10256 (1998).

    Article  CAS  Google Scholar 

  12. Kiehn, O., Johnson, B. R. & Raastad, M. Plateau properties in mammalian spinal interneurons during transmitter-induced locomotor activity. Neuroscience 75, 263–273 (1996).

    Article  CAS  Google Scholar 

  13. Harris-Warrick, R. M. & Marder, E. Modulation of neural networks for behavior. Annu. Rev. Neurosci. 14, 39–57 (1991).

    Article  CAS  Google Scholar 

  14. Steriade, M., McCormick, D. A. & Sejnowski, T. J. Thalamocortical oscillations in the sleeping and aroused brain. Science 262, 679–685 (1993).

    Article  CAS  Google Scholar 

  15. Rekling, J. C. & Feldman, J. L. PreBotzinger complex and pacemaker neurons: hypothesized site and kernel for respiratory rhythm generation. Annu. Rev. Physiol. 60, 385–405 (1998).

    Article  CAS  Google Scholar 

  16. Koshiya, N. & Smith, J. C. Neuronal pacemaker for breathing visualized in vitro. Nature 400, 360–363 (1999).

    Article  CAS  Google Scholar 

  17. Kiehn, O., Hounsgaard, J. & Sillar, K. T. in Neurons, Networks and Motor Behavior (eds. Stein, P. S. G., Grillner, S., Selverston, A. I. & Stuart, D. G.) 47–59 (MIT Press, Cambridge, Massachusetts, 1997).

    Google Scholar 

  18. Wallen, P. & Grillner, S. N-methyl-d-aspartate receptor-induced, inherent oscillatory activity in neurons active during fictive locomotion in the lamprey. J. Neurosci. 7, 2745–2755 (1987).

    Article  CAS  Google Scholar 

  19. Sillar, K. T. & Simmers, A. J. Oscillatory membrane properties of spinal cord neurons that are active during fictive swimming in Rana temporaria embryos. Eur. J. Morphol. 32, 185–192 (1994).

    CAS  PubMed  Google Scholar 

  20. MacLean, J., Schmidt, B. J. & Hochman, S. NMDA receptor activation triggers voltage oscillations, plateau potentials and bursting in neonatal rat lumbar motoneurons in vitro. Eur. J. Neurosci. 9, 2702–2711 (1997).

    Article  CAS  Google Scholar 

  21. Moore, L. E., Chub, N., Tabak, J. & O'Donovan, M. NMDA-induced dendritic oscillations during a soma voltage clamp of chick spinal neurons. J. Neurosci. 19, 8271–8280 (1999).

    Article  CAS  Google Scholar 

  22. Prime, L., Pichon, Y. & Moore, L. E. N-Methyl-d-aspartate-induced oscillations in whole cell clamped neurons from the isolated spinal cord of Xenopus laevis embryos. J. Neurophysiol. 82, 1069–1073 (1999).

    Article  CAS  Google Scholar 

  23. Sillar, K. T. & Simmers, A. J. Electrical coupling and intrinsic neuronal oscillations in Rana temporaria spinal cord. Eur. J. Morphol. 32, 293–298 (1994).

    CAS  PubMed  Google Scholar 

  24. Fulton, B. P., Miledi, R.. & Takahashi, T. K. Electrical synapses between motoneurons in the spinal cord of the newborn rat. Proc. R. Soc. Lond. B Biol. Sci. 208, 115–120 (1980).

    Article  CAS  Google Scholar 

  25. Walton, K. D. & Navarrete, R. Postnatal changes in motoneurone electrotonic coupling studied in the in vitro rat lumbar spinal cord. J. Physiol. (Lond.) 433, 283–305 (1991).

    Article  CAS  Google Scholar 

  26. Rekling, J. C. & Feldman, J. L. Bidirectional electrical coupling between inspiratory motoneurons in the newborn mouse nucleus ambiguus. J. Neurophysiol. 78, 3508–3510 (1997).

    Article  CAS  Google Scholar 

  27. Chang, Q., Gonzalez, M., Pinter, M. J. & Balice-Gordon, R. J. Gap junctional coupling and patterns of connexin expression among neonatal rat lumbar spinal motor neurons. J. Neurosci. 19, 10813–10828 (1999).

    Article  CAS  Google Scholar 

  28. Rash, J. E. et al. Mixed synapses discovered and mapped throughout mammalian spinal cord. Proc. Natl. Acad. Sci. USA 93, 4235–4239 (1996).

    Article  CAS  Google Scholar 

  29. van der Want, J. J., Gramsbergen, A., Ijkema-Paassen, J., de Weerd, H. & Liem, R. S. Dendro-dendritic connections between motoneurons in the rat spinal cord: an electron microscopic investigation. Brain Res. 779, 342–345 (1998).

    Article  CAS  Google Scholar 

  30. Haydon, D. A. & Urban, B. W. The actions of some general anaesthetics on the potassium current of the squid giant axon. J. Physiol. (Lond.) 373, 311–327 (1986).

    Article  CAS  Google Scholar 

  31. Kepler, T. B., Marder, E. & Abbott, L. F. The effect of electrical coupling on the frequency of model neuronal oscillators. Science 248, 83–85 (1990).

    Article  CAS  Google Scholar 

  32. Sherman, A. & Rinzel, J. Rhythmogenic effects of weak electrotonic coupling in neuronal models. Proc. Natl. Acad. Sci. USA 89, 2471–2474 (1992).

    Article  CAS  Google Scholar 

  33. Smolen, P., Rinzel, J. & Sherman, A. Why pancreatic islets burst but single beta cells do not. The heterogeneity hypothesis. J. Biophys. 64, 1668–1680 (1993).

    Article  CAS  Google Scholar 

  34. Manor, Y., Rinzel, J., Segev, I. & Yarom, Y. Low-amplitude oscillations in the inferior olive: a model based on electrical coupling of neurons with heterogeneous channel densities. J. Neurophysiol. 77, 2736–2752 (1997).

    Article  CAS  Google Scholar 

  35. Nowak, L., Bregetovski, P., Ascher, P., Herbert, A. & Prochiantz, A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307, 462–465 (1984).

    Article  CAS  Google Scholar 

  36. Kiehn, O. & Kjaerulff, O. in Neuronal Mechanisms for Generating Locomotor Activity (eds. Kiehn, O., Harris-Warrick, R. M., Jordan, L. M., Hultborn, H. & Kudo, N.) 110–129 (New York Academy of Sciences, New York, 1998).

    Google Scholar 

  37. Matsushima, T. & Grillner, S. Neural mechanisms of intersegmental coordination in lamprey: local excitability changes modify the phase coupling along the spinal cord. J. Neurophysiol. 67, 373–388 (1992).

    Article  CAS  Google Scholar 

  38. Milner, L. D. & Landmesser, L. T. Cholinergic and GABAergic inputs drive patterned spontaneous motoneuron activity before target contact. J. Neurosci. 19, 3007–3022 (1999).

    Article  CAS  Google Scholar 

  39. Jefferys, J. G. Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. Physiol. Rev. 75, 689–723 (1995).

    Article  CAS  Google Scholar 

  40. Kandler, K. & Katz, L. C. Neuronal coupling and uncoupling in the developing nervous system. Curr. Opin. Neurobiol. 5, 98–105 (1995).

    Article  CAS  Google Scholar 

  41. Bennett, M. V. Gap junctions as electrical synapses. J. Neurocytol. 26, 349–366 (1997).

    Article  CAS  Google Scholar 

  42. Chang, Q., Pereda, A., Pinter, M. J. & Balice-Gordon, R. J. Nerve injury induces gap junctional coupling among axotomized adult motor neurons. J. Neurosci. 20, 674–684 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Danish Medical Research Council and the Novo Foundation. M.C.T. is a Postdoctoral Research Fellow supported by the Lundbeck Foundation. We thank Emilio Bizzi, Jorn Hounsgaard, Henrik Jahnsen and Jean-Francois Perrier for reading the manuscript and Hiroshi Nishimaru for suggesting the use of carbenoxolone.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ole Kiehn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tresch, M., Kiehn, O. Motor coordination without action potentials in the mammalian spinal cord. Nat Neurosci 3, 593–599 (2000). https://doi.org/10.1038/75768

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/75768

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing