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A physiological role for endogenous zinc in rat hippocampal synaptic neurotransmission

Abstract

THE mammalian central nervous system (CNS) contains an abundance of the transition metal zinc, which is highly localized in the neuronal parenchyma1–4. Zinc is actively taken up5,6 and stored in synaptic vesicles in nerve terminals7–10, and stimulation of nerve fibre tracts that contain large amounts of zinc, such as the hippocampal mossy fibre system4, can induce its release11–13, suggesting that it may act as a neuromodulator. The known interaction of zinc with the major excitatory and inhibitory amino-acid neurotransmitter receptors in the CNS supports this notion14–16. That zinc has a role in CNS synaptic transmission, however, has so far not been shown. Here we report a physiological role for zinc in the young rat hippocampus (postnatal, P3–P14 days). Our results indicate that naturally occurring spontaneous giant depolarizing synaptic potentials (GDPs) in young CA3 pyramidal neurones, mediated by the release of GAB A (γ-aminobutyric acid)17, are induced by endogenously released zinc. These synaptic potentials are inhibited by specific zinc-chelating agents. GDPs are apparently generated by an inhibitory action of zinc on both pre- and postsynaptic GABAB receptors in the hippocampus. Our study implies that zinc modulates synaptic transmission in the immature hippocampus, a finding that may have implications for understanding benign postnatal seizures in young children suffering with acute zinc deficiency18.

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References

  1. Danscher, G. in The Neurobiology of Zinc Vol. A (eds Frederickson, C. J., Howell, G. A. & Kasarskis, E. J.) 227–242 (Alan Liss, New York, 1984).

    Google Scholar 

  2. Frederickson, C. J., Kasarskis, E. J., Ringo, D. & Frederickson, R. E. J. Neurosci. Meth. 20, 91–103 (1987).

    Article  CAS  Google Scholar 

  3. Crawford, I. L. & Connor, J. D. J. Neurochem. 19, 1451–1458 (1972).

    Article  CAS  Google Scholar 

  4. Frederickson, C. J. Int. Rev. Neurobiol. 31, 145–238 (1989).

    Article  CAS  Google Scholar 

  5. Wolf, G., Schutte, M. & Romhild, W. Neuroscience Lett. 51, 277–280 (1984).

    Article  CAS  Google Scholar 

  6. Wensink, J., Molenaar, A. J., Woroniecka, U. D. & Van Den Hamer, C. J. J. Neurochem. 50, 783–789 (1988).

    Article  Google Scholar 

  7. Ibata, Y. & Otsuka, N. J. Histochem. Cytochem. 17, 171–175 (1969).

    Article  CAS  Google Scholar 

  8. Perez-Clausell, J. & Danscher, G. Brain Res. 337, 91–98 (1985).

    Article  CAS  Google Scholar 

  9. Friedman, B. & Price, J. L. J. Comp. Neurol. 223, 88–109 (1984).

    Article  CAS  Google Scholar 

  10. Holm, I. E., Andreasen, A., Danscher, G., Perez-Clausell, J. & Nielsen, H. Histochem. 89, 289–293 (1988).

    Article  CAS  Google Scholar 

  11. Assaf, S. Y. & Chung, S. H. Nature 308, 734–736 (1984).

    Article  ADS  CAS  Google Scholar 

  12. Howell, G. A., Welch, M. G. & Frederickson, C. J. Nature 308, 736–738 (1984).

    Article  ADS  CAS  Google Scholar 

  13. Charlton, G., Rovira, C., Ben-Ari, Y. & Leviel, V. Exp. Brain Res. 58, 202–205 (1985).

    Google Scholar 

  14. Peters, S., Koh, J. & Choi, D. W. Science 236, 589–593 (1987).

    Article  ADS  CAS  Google Scholar 

  15. Westbrook, G. L. & Mayer, M. L. Nature 328, 640–643 (1987).

    Article  ADS  CAS  Google Scholar 

  16. Smart, T. G. & Constanti, A. Brit. J. Pharmacol. 99, 643–654 (1990).

    Article  CAS  Google Scholar 

  17. Ben-Ari, Y., Cherubini, E., Corradetti, R. & Gaiarsa, J. L. J. Physiol. 416, 303–325 (1989).

    Article  CAS  Google Scholar 

  18. Goldberg, J. & Sheehy, E. M. Arch. Dis. Child 57, 633–635 (1982).

    Article  CAS  Google Scholar 

  19. Hider, R. C. et al. Biochem. Pharmac. 39, 1005–1012 (1990).

    Article  CAS  Google Scholar 

  20. Alger, B. E. & Nicoll, R. A. J. Physiol. 328, 105–123 (1982).

    Article  CAS  Google Scholar 

  21. Dutar, P. & Nicoll, R. A. Nature 332, 156–158 (1988).

    Article  ADS  CAS  Google Scholar 

  22. Hill, D. R. & Bowery, N. G. Nature 290, 149–152 (1981).

    Article  ADS  CAS  Google Scholar 

  23. Vallee, B. L. & Galdes, A. Adv. Enzymol. Relat. Mol. Biol. 56, 283–430 (1984).

    CAS  Google Scholar 

  24. Crawford, I. L. & Connor, J. D. J. Orthomol. Psychiatry 4, 39–52 (1975).

    CAS  Google Scholar 

  25. Danscher, G., Shipley, M. T. & Andersen, P. Brain Res. 85, 522–526 (1975).

    Article  CAS  Google Scholar 

  26. Doller, H. J. & Crawford, I. L. in The Neurobiology of Zinc Vol. B (eds Frederickson, C. J., Howell, G. A. & Kasarskis, E. J.) 163–176 (Alan Liss, New York, 1984).

    Google Scholar 

  27. Hesse, G. W. Science 205, 1005–1007 (1979).

    Article  ADS  CAS  Google Scholar 

  28. Andersen, P., Dingledine, R., Gjerstad, L., Langmoen, I. A. & Mosfeldt Laursen, A. J. Physiol. 305, 279–296 (1980).

    Article  CAS  Google Scholar 

  29. McLaughlin, B. J., Wood, J. G., Saito, K., Roberts, E. & Wu, J.-Y. Brain Res. 85, 355–371 (1975).

    Article  CAS  Google Scholar 

  30. Schwartzkroin, P. A. Dev. Brain Res. 2, 469–486 (1982).

    Article  Google Scholar 

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Xie, X., Smart, T. A physiological role for endogenous zinc in rat hippocampal synaptic neurotransmission. Nature 349, 521–524 (1991). https://doi.org/10.1038/349521a0

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