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Neurokinin-1 receptor-expressing neurons in the ventral medulla are essential for normal central and peripheral chemoreception in the conscious rat

Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire

Submitted 22 March 2006 ; accepted in final form 4 August 2006

Neurokinin-1 receptor immunoreactive (NK1R-ir) neurons and processes are widely distributed within the medulla, prominently at central chemoreceptor sites. Focal lesions of NK1R-ir neurons in the medullary raphe or the retrotrapezoid nucleus partially reduced the CO₂ response in conscious rats. We ask if NK1R-ir cells and processes over a wide region of the ventral medulla are essential for central and peripheral chemoreception by cisterna magna injection of SSP-SAP, a high-affinity version of substance P-saporin. After 22 days, NK1R-ir cell loss was –79% in the retrotrapezoid nucleus and –65% in the A5 region, which lie close to the ventral surface, and –38% in the medullary raphe and –49% in the pre-Bötzinger complex/rostral ventral respiratory group, which lie deeper. Dorsal chemoreceptor sites, the caudal nucleus tractus solitarius and the A6 region, were unaffected. At 8 and 22 days, these lesions produced 1) hypoventilation during air breathing in wakefulness (8%) and in non-rapid eye movement (NREM) (9%) and rapid eye movement (14%) sleep, as measured over a 4-h period; 2) a substantially reduced ventilatory response to 7% CO₂ by 61% in wakefulness and 46–57% in NREM sleep; and 3) a decreased ventilatory response to 12% O₂ by 40% in wakefulness and 35% in NREM sleep at 8 days, with partial recovery by 22 days. NK1R-ir neurons in the ventral medulla are essential for normal central chemoreception, provide a drive to breathe, and modulate the peripheral chemoreceptor responses. These effects are not state dependent.

substance P; control of breathing; retrotrapezoid nucleus; medullary raphe; A5

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				P. G. Guyenet, R. L. Stornetta, and D. A. Bayliss Retrotrapezoid nucleus and central chemoreception J. Physiol., April 15, 2008; 586(8): 2043 - 2048. [Abstract] [Full Text] [PDF]