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Sleep-disordered breathing after targeted ablation of preBötzinger complex neurons

Abstract

Ablation of preBötzinger complex (preBötC) neurons, critical for respiratory rhythm generation, resulted in a progressive, increasingly severe disruption of respiratory pattern, initially during sleep and then also during wakefulness in adult rats. Sleep-disordered breathing is highly prevalent in elderly humans and in some patients with neurodegenerative disease. We propose that sleep-disordered breathing results from loss of preBötC neurons and could underlie death during sleep in these populations.

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Figure 1: Breathing pattern is progressively disrupted, initially during sleep and then also during wakefulness.
Figure 2: Number and duration of respiratory disturbances (apneas and hypopneas).
Figure 3: Respiration and sleep become highly fragmented.

References

  1. Krieger, J., Turlot, J.C., Mangin, P. & Kurtz, D. Sleep 6, 108–120 (1983).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Feldman, J.L., Mitchell, G.S. & Nattie, E.E. Annu. Rev. Neurosci. 26, 239–266 (2003).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Mendelson, W.B. et al. Physiol. Behav. 43, 229–234 (1988).

    Article  CAS  Google Scholar 

  7. Siegel, J.M. J. Clin. Psychiatry 65 (suppl.), 4–7 (2004).

    CAS  Google Scholar 

  8. Ferguson, K.A., Strong, M.J., Ahmad, D. & George, C.F. Chest 110, 664–669 (1996).

    Article  CAS  Google Scholar 

  9. Munschauer, F.E., Loh, L., Bannister, R. & Newsom-Davis, J. Neurology 40, 677–679 (1990).

    Article  CAS  Google Scholar 

  10. Maria, B. et al. Respir. Med. 97, 1151–1157 (2003).

    Article  Google Scholar 

  11. Benarroch, E.E., Schmeichel, A.M., Low, P.A. & Parisi, J.E. Brain 126, 2183–2190 (2003).

    Article  Google Scholar 

  12. Alexianu, M.E. et al. Ann. Neurol. 36, 846–858 (1994).

    Article  CAS  Google Scholar 

  13. Alheid, G.F., Gray, P.A., Jiang, M.C., Feldman, J.L. & McCrimmon, D.R. J. Neurocytol. 31, 693–717 (2002).

    Article  CAS  Google Scholar 

  14. Berry, R.B. & Gleeson, K. Sleep 20, 654–675 (1997).

    Article  CAS  Google Scholar 

  15. Leung, R.S. & Bradley, T.D. Am. J. Respir. Crit. Care Med. 164, 2147–2165 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to J.M. Siegel for his insightful advice; we thank G.S. Mitchell, C.A. Del Negro, L. Kruger, N. Dale and P.A. Gray for comments on the manuscript and G. Li for histological assistance. This work was supported by US National Institutes of Health grant HL70029.

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Correspondence to Jack L Feldman.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

SP-SAP specifically ablates NK1R neurons within the preBötC. (PDF 1601 kb)

Supplementary Fig. 2

Continuous 5 minute physiological recordings pre-injection (control). (PDF 4929 kb)

Supplementary Fig. 3

Continuous 5 minute physiological recordings on day 4 post-injection. (PDF 4927 kb)

Supplementary Fig. 4

Continuous 5 minute physiological recordings on day 6 post-injection. (PDF 4945 kb)

Supplementary Fig. 5

Continuous 5 minute physiological recordings on day 8 post-injection. (PDF 4860 kb)

Supplementary Fig. 6

Continuous 5 minute physiological recordings on day 10 post-injection. (PDF 4428 kb)

Supplementary Video 1

Integrated diaphragm and neck EMG tracings illustrate respiratory activity and changes in sleep/wake state respectively. The audio sound is diaphragm EMG activity. Wakefulness, NREM and REM are denoted on the timeline by green, blue and pink bars respectively. The moving arrow relates the EMG tracings to the appropriate time point in the movie. Central apneas, characterized by absence of ∫DIAEMG and sound, are denoted by a red bar on the timeline. Hypopnea typically begins in NREM leading to a central apnea (note change in ∫DIAEMG and sound) as sleep progresses into REM. Breathing resumes when the rat abruptly awakens (note change in neck EMG during sleep/wake transitions). Breathing during wake is regular but with a higher frequency compared to pre-injection. This cycle is repeated several times over 1½ minutes. (MOV 3665 kb)

Supplementary Methods (PDF 124 kb)

Supplementary Note (PDF 51 kb)

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McKay, L., Janczewski, W. & Feldman, J. Sleep-disordered breathing after targeted ablation of preBötzinger complex neurons. Nat Neurosci 8, 1142–1144 (2005). https://doi.org/10.1038/nn1517

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