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Hippocampal synaptic transmission enhanced by low concentrations of nicotine

Abstract

NICOTINE obtained from tobacco can improve learning and memory on various tasks and has been linked to arousal, attention, rapid information processing, working memory, and long-term memories that can cause craving years after someone has stopped smoking1,2. One likely target for these effects is the hippocampus, a centre for learning and memory that has rich cholinergic innervation and dense nicotinic acetylcholine receptor (nAChR) expression3–6. During Alzheimer's dementia there are fewer nAChRs and the cholinergic inputs to the hippocampus degenerate7. However, there is no evidence for fast synaptic transmission mediated by nAChRs in the hippocampus, and their role is not understood8,9. Nicotine is known to act on presynaptic nAChRs within the habenula of chick to enhance glutamatergic transmission10; here we report that a similar mechanism operates in the hippocampus. Measurements of intracellular Ca2+ in single mossy-fibre presynaptic terminals indicate that nAChRs containing the α7 subunit can mediate a Ca2+ influx that is sufficient to induce vesicular neurotransmitter release. We propose that nicotine from tobacco influences cognition by enhancing synaptic transmission. Conversely, a decreased efficacy of transmission may account for the deficits associated with the loss of cholinergic innervation during Alzheimer's disease.

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References

  1. Levin, E. D. Psychopharmacology 108, 417–431 (1992).

    Article  CAS  Google Scholar 

  2. Ohno, M., Yamamoto, T. & Watanabe, S. Pharmacol. Biochem. Behav. 45, 89–93 (1993).

    Article  CAS  Google Scholar 

  3. Kasa, P. Prog. Neurobiol. 26, 211–272 (1986).

    Article  CAS  Google Scholar 

  4. Woolf, N. J. Prog. Neurobiol. 37, 475–524 (1991).

    Article  CAS  Google Scholar 

  5. Séguéla, P., Wadiche, J., Dineley-Miller, K., Dani, J. A. & Patrick J. W. J. Neurosci. 13, 596–604 (1993).

    Article  Google Scholar 

  6. Wada, E. et al. J. Comp. Neurol. 284, 314–335 (1989).

    Article  CAS  Google Scholar 

  7. Nordberg, A. Neurochem. Int. 25, 93–97 (1994).

    Article  CAS  Google Scholar 

  8. Sargent, P. Annu. Rev. Neurosci. 16, 403–443 (1993).

    Article  CAS  Google Scholar 

  9. McGehee, D. S. & Role, L. W. Annu. Rev. Physiol. 57, 521–546 (1995).

    Article  CAS  Google Scholar 

  10. McGehee, D. S., Heath, M. J. S., Gelber, S., Devay, P. & Role, L. W. Science 269, 1692–1696 (1995).

    Article  ADS  CAS  Google Scholar 

  11. Henningfield, J. E., Stapleton, J. M., Benowitz, N. L., Grayson, R. F. & London, E. D. Drug Alcohol Depend. 33, 23–29 (1993).

    Article  CAS  Google Scholar 

  12. Alkondon, M. & Albuquerque, E. X. J. Recept. Res. 11, 1001–1021 (1991).

    Article  CAS  Google Scholar 

  13. Alkondon, M., Pereira, E. F., Wonnacott, S. & Albuquerque, E. X. Mol. Pharmacol. 41, 802–808 (1992).

    CAS  PubMed  Google Scholar 

  14. Zorumski, C. F., Thio, L. L., Isenberg, K. E. & Clifford, D. B. Mol. Pharmacol. 41, 931–936 (1992).

    CAS  PubMed  Google Scholar 

  15. Alkondon, M. & Albuquerque, E. X. J. Pharmacol. Exp. Ther. 265, 1455–1473 (1993).

    CAS  PubMed  Google Scholar 

  16. Couturier, S. et al. Neuron 5, 847–856 (1990).

    Article  CAS  Google Scholar 

  17. Vernino, S., Amador, M., Luetje, C. W., Patrick, J. & Dani, J. A. Neuron 8, 127–135 (1992).

    Article  CAS  Google Scholar 

  18. Vijayaraghavan, S., Pugh, P. C., Zhang, Z., Rathouz, M. M. & Berg, D. K. Neuron 8, 353–362 (1992).

    Article  CAS  Google Scholar 

  19. Vernino, S., Rogers, M., Radcliffe, K. A. & Dani, J. A. J. Neurosci. 14, 5514–5524 (1994).

    Article  CAS  Google Scholar 

  20. Castro, N. G. & Albuquerque, E. X. Biophys. J. 68, 516–524 (1995).

    Article  ADS  CAS  Google Scholar 

  21. Llinás, R., Sugimori, M. & Silver, R. B. Science 256, 677–679 (1992).

    Article  ADS  Google Scholar 

  22. Wu, L. G. & Saggau, P. J. Neurosci. 14, 645–654 (1994).

    Article  CAS  Google Scholar 

  23. Stevens, C. F. & Wang, Y. Neuron 14, 795–802 (1995).

    Article  CAS  Google Scholar 

  24. Wonnacott, S., Drasdo, A., Sanderson, E. & Rowell, P. in The Biology of Nicotine Dependence (eds Bock, G. & Marsh, J.) 87–105 (John Wiley, New York, 1990).

    Google Scholar 

  25. Dani, J. A. & Heinemann, S. Neuron 16, 905–908 (1996).

    Article  CAS  Google Scholar 

  26. Magee, J. C. & Johnston, D. J. Physiol. (Lond.) 487, 67–90 (1995).

    Article  CAS  Google Scholar 

  27. Stuart, G. J., Dodt, H. U. & Sakmann, B. Pflugers Arch. 423, 511–518 (1993).

    Article  CAS  Google Scholar 

  28. Zarei, M. M. & Dani, J. A. J. Neurosci. 15, 1446–1454 (1995).

    Article  CAS  Google Scholar 

  29. Rae, J., Cooper, K., Gates, P. & Watsky, M. J. Neurosci. Methods 37, 15–26 (1991).

    Article  CAS  Google Scholar 

  30. Lev-Ram, V., Miyakawa, H., Lasser-Ross, N. & Ross, W. N. J. Neurophysiol. 68, 1167–1177 (1992).

    Article  CAS  Google Scholar 

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Gray, R., Rajan, A., Radcliffe, K. et al. Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 383, 713–716 (1996). https://doi.org/10.1038/383713a0

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