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Silent glutamatergic synapses and nociception in mammalian spinal cord

Abstract

Neurons in the superficial dorsal horn of the spinal cord are important for conveying sensory information from the periphery to the central nervous system1,2. Some synapses between primary afferent fibres and spinal dorsal horn neurons may be inefficient or silent3. Ineffective sensory transmission could result from a small postsynaptic current that fails to depolarize the cell to threshold for an action potential or from a cell with a normal postsynaptic current but an increased threshold for action potentials. Here we show that some cells in the superficial dorsal horn of the lumbar spinal cord have silent synapses: they do not respond unless the holding potential is moved from −70 mV to +40 mV. Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter of the raphe–spinal projecting pathway, transforms silent glutamatergic synapses into functional ones. Therefore, transformation of silent glutamatergic synapses may serve as a cellular mechanism for central plasticity in the spinal cord.

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Figure 1: Silent glutamatergic synapses in the lumbar spinal cord.
Figure 2: Biphasic modulation induced by 5-HT.
Figure 3: Transformation of silent synapses into functional synapses by 5-HT or DOI.
Figure 4: Dependence on postsynaptic G proteins and intracellular Ca2+.

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References

  1. Kumazawa, T. & Perl, E. R. Excitation of marginal and substantia gelatinosa neurons in the primate spinal cord: indications of their place in dorsal horn functional organization. J. Comp. Neurol. 177, 417–434 (1978).

    Article  CAS  Google Scholar 

  2. Light, A. R., Trevino, D. L. & Perl, E. R. Morphological features of functionally defined neurons in the marginal zone and substantia gelatinosa of the spinal dorsal horn. J. Comp. Neurol. 186, 151–171 (1979).

    Article  CAS  Google Scholar 

  3. Wall, P. D. The presence of ineffective synapses and the circumstances which unmask them. Phil. Trans. R. Soc. Lond. B 278, 361–372 (1977).

    Article  ADS  CAS  Google Scholar 

  4. Liao, D., Hessler, N. A. & Malinow, R. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375, 400–404 (1995).

    Article  ADS  CAS  Google Scholar 

  5. Isaac, J. T. R., Nicoll, R. A. & Malenka, R. C. Evidence for silent synapses: implications for the expression of LTP. Neuron 15, 427–434 (1995).

    Article  CAS  Google Scholar 

  6. Isaac, J. T. R., Crair, M. C., Nicoll, R. A. & Malenka, R. C. Silent synapses during development of thalamocortical inputs. Neuron 18, 269–280 (1997).

    Article  CAS  Google Scholar 

  7. Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71–75 (1996).

    Article  ADS  CAS  Google Scholar 

  8. Wu, G.-Y., Malinow, R. & Cline, H. T. Maturation of a central glutamatergic synapse. Science 274, 972–976 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Malenka, R. C. & Nicoll, R. A. Silent synapses speak up. Neuron 19, 473–476 (1997).

    Article  CAS  Google Scholar 

  10. Yoshimura, M. & Jessell, T. M. Amino acid-mediated EPSPs at primary afferent synapses with substantia gelatinosa neurones in the rat spinal cord. J. Physiol. Lond. 430, 315–335 (1990).

    Article  CAS  Google Scholar 

  11. Randic, M., Jiang, M. C. & Cerne, R. Long-term potentiation and Long-term depression of primary afferent neurotransmission in the rat spinal cord. J. Neurosci. 13, 5228–5241 (1993).

    Article  CAS  Google Scholar 

  12. Hori, Y., Endo, K. & Takahashi, T. Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of the rat spinal cord. J. Physiol. Lond. 492, 867–876 (1996).

    Article  CAS  Google Scholar 

  13. Gebhart, G. F. & Randich, A. in Brainstem Mechanisms of Behaviour (eds Klemm, W. R. & Vertes, R. P.) 315–352 (Wiley, New York, (1990)).

    Google Scholar 

  14. Fields, H. L., Heinricher, M. M. & Mason, P. Neurotransmitters in nociceptive modulatory circuits. Annu. Rev. Neurosci. 14, 219–245 (1991).

    Article  CAS  Google Scholar 

  15. Zhuo, M. & Gebhart, G. F. Spinal serotonin receptors mediate descending facilitation of a nociceptive reflex from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. Brain Res. 550, 35–48 (1991).

    Article  CAS  Google Scholar 

  16. Zhuo, M. & Gebhart, G. F. Characterization of descending facilitation and inhibition of spinal nociceptive transmission from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. J. Neurophysiol. 67, 1599–1614 (1992).

    Article  CAS  Google Scholar 

  17. Zhuo, M. & Gebhart, G. F. Biphasic modulation of spinal nociceptive transmission from the medullary raphe nuclei in the rat. J. Neurophysiol. 78, 746–758 (1997).

    Article  CAS  Google Scholar 

  18. Todd, A. J., Spike, R. C., Price, R. F. & Neilson, M. Immunocytochemical evidence that neurotension is present in glutamatergic neurons in the superficial dorsal horn of the rat. J. Neurosci. 14, 774–784 (1994).

    Article  CAS  Google Scholar 

  19. Stevens, C. F. & Wang, Y. Changes in reliability of synaptic function as a mechanism for plasticity. Nature 371, 704–707 (1994).

    Article  ADS  CAS  Google Scholar 

  20. Lopez-Garcia, J. A. & King, A. E. Pre- and post-synaptic actions of 5-hydroxytryptamine in the rat lumbar dorsal horn in vitro: implications for somatosensory transmission. Eur. J. Neurosci. 8, 2188–2197 (1996).

    Article  CAS  Google Scholar 

  21. Singer, W. Development and plasticity of cortical processing architectures. Science 270, 758–764 (1995).

    Article  ADS  CAS  Google Scholar 

  22. Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996).

    Article  ADS  CAS  Google Scholar 

  23. Menetrey, D. & Besson, J. M. Electrophysiological characteristic of dorsal horn cells in rats with cutaneous inflammation resulting from chronic arthritis. Pain 13, 343–364 (1982).

    Article  CAS  Google Scholar 

  24. Hylden, J. L. K., Nahin, R. L., Traub, R. J. & Dubner, R. Expansion of receptive fields of spinal lamina I projection neurons in rats with unilateral adjuvant-induced inflammation: the contribution of dorsal horn mechanisms. Pain 37, 229–243 (1989).

    Article  CAS  Google Scholar 

  25. Dubner, R. & Ruda, M. A. Activity-dependent neuronal plasticity following tissue injury and inflammation. Trends Neurosci. 15, 96–103 (1992).

    Article  CAS  Google Scholar 

  26. Harris, J. A., Corsi, M., Quartaroli, M., Arban, R. & Bentivoglio, M. Upregulation of spinal glutamate receptors in chronic pain. Neuroscience 14, 7–12 (1996).

    Article  Google Scholar 

  27. Maccaferri, G. & McBain, C. J. Long-term potentiation in distinct subtypes of hippocampal nonpyramidal neurons. J. Neurosci. 16, 5334–5343 (1996).

    Article  CAS  Google Scholar 

  28. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Compact 3rd edn CD-Rom; Academic, San Diego, (1997)).

    Google Scholar 

  29. Beyer, W. H. (ed. Handbook of Tables for Probability and Statistics 2nd edn. (Chemical Rubber Company, Cleveland, (1968).

    Google Scholar 

Download references

Acknowledgements

We thank R. W. Tsien and J. H. Steinbach for reviewing the manuscript, N. Gautam for discussion, P. Mason for communication of unpublished data, and G. Maccaferri, J. Li, E. T. Kavalali and X. D. Yang for technical advice. This work was supported in part by a grant from the NIDA.

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Correspondence to Min Zhuo.

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Li, P., Zhuo, M. Silent glutamatergic synapses and nociception in mammalian spinal cord. Nature 393, 695–698 (1998). https://doi.org/10.1038/31496

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