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A cortical neuropeptide with neuronal depressant and sleep-modulating properties

Abstract

ACETYLCHOLINE (ACh) plays a key role in the transitions between the different phases of sleep1: Slow-wave sleep requires low ACh concentrations in the brain, whereas rapid-eye-movement (REM) sleep is associated with high levels of ACh. Also, these phases of sleep are differentially sensitive to a number of endogenous neuropeptides and cytokines, including somatostatin, which has been shown to increase REM sleep without significantly affecting other phases2. Here we report the cloning and initial characterization of cortistatin, a neuropeptide that exhibits strong structural similarity to somatostatin, although it is the product of a different gene. Administration of cortistatin depresses neuronal electrical activity but, unlike somatostatin, induces low-frequency waves in the cerebral cortex and antagonizes the effects of acetylcholine on hippocampal and cortical measures of excitability. This suggests a mechanism for cortical synchronization related to sleep.

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References

  1. Shiromani, P. J., Gillin, J. C. & Henriksen, S. J. A. Rev. Pharmac. Toxicol. 27, 137–56 (1987).

    Article  CAS  Google Scholar 

  2. Borbely, A. A. & Tobler, I. Physiol. Rev. 69, 605–670 (1989).

    Article  CAS  Google Scholar 

  3. Glushankov, P. et al. Proc. natn. Acacf. Sci. U.S.A. 81, 6662–6666 (1984).

    Article  ADS  Google Scholar 

  4. Veber, D. F. et al. Nature 280, 512–514 (1979).

    Article  ADS  CAS  Google Scholar 

  5. Erlander, M. G. et al. Neuron 7, 91–100 (1991).

    Article  CAS  Google Scholar 

  6. Schonbrunn, A. H. & Tashijan, A. J. R., J. biol. Chem. 235, 6473–6483 (1978).

    Google Scholar 

  7. Halliwell, J. V. & Adams, P. R. Brain Res. 250, 71–92 (1982).

    Article  CAS  Google Scholar 

  8. Moore, S. D. et al. Science 239, 278–280 (1988).

    Article  ADS  CAS  Google Scholar 

  9. Schweitzer, P., Madamba, S. & Siggins, G. R. Nature 346, 464–466 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Andersen, P., Bliss, T. V. P. & Skrede, K. K. Expl Brain Res. 13, 208–221 (1971).

    CAS  Google Scholar 

  11. Danguir, J. Brain Res. 367, 26–30 (1986).

    Article  CAS  Google Scholar 

  12. Steriade, M., McCormick, D. A. & Sejnowski, T. J. Science 262, 679–685 (1993).

    Article  ADS  CAS  Google Scholar 

  13. Andersen, P., Eccles, J. C. & Løyning, Y. J. Neurophysiol. 27, 607–619 (1964).

    Google Scholar 

  14. Kandel, E. R. & Spencer, W. A. J. Neurophysiol. 24, 243–259 (1961).

    Article  CAS  Google Scholar 

  15. Steffensen, S. & Henriksen, S. J. Brain Res. 538, 46–53 (1991).

    Article  CAS  Google Scholar 

  16. Maurer, R. et al. Proc. natn. Acad. Sci. U.S.A. 79, 4815–4817 (1982).

    Article  ADS  CAS  Google Scholar 

  17. Scharfman, H. E. & Schwartzkroin, P. A. Brain Res. 493, 205–211 (1989).

    Article  CAS  Google Scholar 

  18. deLecea, L. et al. Molec. Brain Res. 25, 286–296 (1994).

    Article  CAS  Google Scholar 

  19. Schweitzer, P. et al. J. Neurosci. 13, 2033–2049 (1993).

    Article  CAS  Google Scholar 

  20. Prospero-Garcia, O., Criado, J. R. & Henriksen, S. J. Pharmac. Biochem. Behav. 49, 413 (1994).

    Article  CAS  Google Scholar 

  21. Steffensen, S. C., Campbell, I. L. & Henriksen, S. J. Brain Res. 652, 149 (1994).

    Article  CAS  Google Scholar 

Download references

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de Lecea, L., Criado, J., Prospero-Garcia, Ó. et al. A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature 381, 242–245 (1996). https://doi.org/10.1038/381242a0

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