Silencing preBötzinger Complex somatostatin-expressing neurons induces persistent apnea in awake rat

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Abstract

Delineating neurons that underlie complex behaviors is of fundamental interest. Using adeno-associated virus 2, we expressed the Drosophila allatostatin receptor in somatostatin (Sst)-expressing neurons in the preBötzinger Complex (preBötC). Rapid silencing of these neurons in awake rats induced a persistent apnea without any respiratory movements to rescue their breathing. We hypothesize that breathing requires preBötC Sst neurons and that their sudden depression can lead to serious, even fatal, respiratory failure.

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Figure 1: preBötC neurons infected by AAV2 containing a Syn or Sst promoter.
Figure 2: Rapid silencing of AlstR-expressing preBötC Sst neurons induced apnea in anesthetized and awake rats.

References

  1. 1

    Gray, P.A., Janczewski, W.A., Mellen, N., McCrimmon, D.R. & Feldman, J.L. Nat. Neurosci. 4, 927–930 (2001).

  2. 2

    Gray, P.A., Rekling, J.C., Bocchiaro, C.M. & Feldman, J.L. Science 286, 1566–1568 (1999).

  3. 3

    Janczewski, W.A. & Feldman, J.L. J. Physiol. (Lond.) 570, 407–420 (2006).

  4. 4

    Smith, J.C., Ellenberger, H.H., Ballanyi, K., Richter, D.W. & Feldman, J.L. Science 254, 726–729 (1991).

  5. 5

    McKay, L.C., Janczewski, W.A. & Feldman, J.L. Nat. Neurosci. 8, 1142–1144 (2005).

  6. 6

    Stornetta, R.L. et al. J. Comp. Neurol. 455, 499–512 (2003).

  7. 7

    Pagliardini, S., Ren, J. & Greer, J.J. J. Neurosci. 23, 9575–9584 (2003).

  8. 8

    Chen, M.L. & Keens, T.G. Paediatr. Respir. Rev. 5, 182–189 (2004).

  9. 9

    Birgul, N., Weise, C., Kreienkamp, H.J. & Richter, D. EMBO J. 18, 5892–5900 (1999).

  10. 10

    Tan, E.M. et al. Neuron 51, 157–170 (2006).

  11. 11

    Callaway, E.M. Trends Neurosci. 28, 196–201 (2005).

  12. 12

    Gosgnach, S. et al. Nature 440, 215–219 (2006).

  13. 13

    Lechner, H.A., Lein, E.S. & Callaway, E.M. J. Neurosci. 22, 5287–5290 (2002).

  14. 14

    Tenenbaum, L. et al. J. Gene Med. 6 (Suppl. 1): S212–S222 (2004).

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Acknowledgements

We thank G. Li for experimental assistance, T. Otis, L. Kruger, K. Kam and S. Pagliardini for comments on the manuscript, and N. Brecha and Y. Nie for advice and technical support. This work was supported by US National Institutes of Health grants HL37941 and HL40959 (J.L.F.).

Author information

Correspondence to Jack L Feldman.

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Supplementary Text and Figures

Supplementary Figures 1–9, Tables 1 and 2, and Methods (PDF 1382 kb)

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