Abstract
The normal breathing rhythm in mammals is hypothesized to be generated by neurokinin-1 receptor (NK1R)-expressing neurons in the preBötzinger complex (preBötC), a medullary region proposed to contain the kernel of the circuits generating respiration. If this hypothesis is correct, then complete destruction of preBötC NK1R neurons should severely perturb and perhaps even fatally arrest breathing. Here we show that specific and near complete bilateral (but not unilateral) destruction of preBötC NK1R neurons results in both an ataxic breathing pattern with markedly altered blood gases and pH, and pathological responses to challenges such as hyperoxia, hypoxia and anesthesia. Thus, these ∼600 neurons seem necessary for the generation of normal breathing in rats.
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Acknowledgements
We thank M. Sofroniew, N. Brecha, T. Otis, R. Fregosi and L. Kruger for assistance and G. Li for histological work. A. Monnier participated in early experiments. Funding was provided by a Ford Foundation Pre-Doctoral Fellowship for Minorities and the Porter Physiology Development Program of the American Physiological Society to P.A.G., and by the National Institutes of Health (HL40959). W.A.J. is on leave of absence from the Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
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Control.mov:
A rat 2 days after injection of SP-SAP that would ultimately produce ~100% bilateral destruction of preB&246;tC NK1R neurons. Because the SP-SAP lesions do not seem to affect breathing before 4-5 days after injection, this rat breathes with an essentially normal pattern. The rat is undrugged and unrestrained. Trace at top is plethysmograph recording; sound is diaphragmatic EMG. (MOV 3546 kb)
Ataxic.mov:
The same rat as in control.mov 8 days after injection, after about 3 days of pathological breathing. The rat is undrugged and unrestrained. Trace at top is integrated diaphragmatic EMG; sound is diaphragmatic EMG. (MOV 7087 kb)
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Gray, P., Janczewski, W., Mellen, N. et al. Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons. Nat Neurosci 4, 927–930 (2001). https://doi.org/10.1038/nn0901-927
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DOI: https://doi.org/10.1038/nn0901-927
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