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Volume 2 Supplement 1

Neural Control of Breathing

PreBötzinger complex (preBötC) neurokinin-1 receptor (NK1R) expressing neurons are required for eupnea in adult awake rats

Normal respiratory rhythm in mammals is hypothesized to be generated by NK1R neurons in the preBötC. Ablation of these neurons in adult rats was predicted to severely perturb normal breathing rhythm. We directly injected substance P conjugated saporin (SP-SAP) into the preBötC to selectively kill NK1R neurons [1]. Four to five days postinjection in rats with greater than 75% bilateral loss of preBötC NK1R neurons, spontaneous breathing rhythm transformed from normal, ie, eupnea, to ataxia, with greatly reduced ventilation and consequent disturbances in blood gases and pH. Hypoxic or hyperoxic challenges produced prolonged, often fatal, apnea. PreBötC NK1R neurons are therefore necessary for generation of the eupneic breathing rhythm.


  1. 1.

    Gray PA, Janczewski WA, Mellen N, McCrimmon DR, Feldman JL: Normal breathing requires preBötzinger Complex neurokinin-1 receptor expressing neurons. Nat Neurosci. 2001,

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Funding was provided by a Ford Foundation Pre-Doctoral Fellowship for Minorities and a predoctoral fellowship from the Porter Physiology Development Program of the American Physiological Society to PAG, and by the NIH Grants HL40959 and HL37941.

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Correspondence to PA Gray.

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About this article


  • Public Health
  • Spontaneous Breathing
  • Respiratory Rhythm
  • Normal Breathing
  • Express Neuron