Journal of Applied Physiology AJP: Advances in Physiology Education
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J Appl Physiol (August 10, 2006). doi:10.1152/japplphysiol.00347.2006
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Submitted on March 22, 2006
Accepted on August 4, 2006

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

Eugene Nattie1* and Aihua Li1

1 Physiology, Dartmouth Medical School, Lebanon, New Hampshire, United States

* To whom correspondence should be addressed. E-mail: eugene.nattie{at}dartmouth.edu.

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-Botzinger 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 a) hypoventilation during air breathing in wakefulness (~8%) and in NREM (~9%) and REM (~14%) sleep as measured over a 4-hour period, b) a substantially reduced ventilatory response to 7% CO2 by 61% in wakefulness and 46-57% in NREM sleep, and c) 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.




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