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1 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
2 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Physical Therapy, Marquette University, Milwaukee, WI, USA
3 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
4 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Physiology, Zablocki VA Medical Center, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: bforster{at}mcw.edu.
In awake rats >80% bilateral reduction of neurokinin-1 receptor (NK1R)-expressing neurons in the pre-Botzinger complex (pre-BotzC) resulted in hypoventilation and an "ataxic" breathing pattern (11). Accordingly, the present study was designed to gain further insight into the role of the pre-BotzC-area NK1R-expressing neurons in the control of breathing during physiologic conditions. Microtubules were chronically implanted bilaterally into the medulla of adult goats. After recovery from surgery, the neurotoxin saporin conjugated to substance P (SP-SAP), specific for NK1R-expressing neurons was bilaterally injected (50pM in 10µl) into the pre-BotzC-area during the awake state (n=8). In un-operated goats, 34±0.01% of the pre-BotzC area neurons are immunoreactive (ir) for the NK1R, but in goats after bilateral injection of SP-SAP into the pre-BotzC area, NK1R-ir was reduced to 22.5±2.5% (29% decrease, P<0.01). Ten to fourteen days after the injection, the frequency of abnormal breathing periods (ABP) was six-fold greater than before injection (107.8±21.8/hr, P < 0.001). Fifty-six percent of these periods were breaths of varying duration and volume with an altered respiratory muscle activation pattern while the remaining were rapid complete breaths with coordinated inspiratory-expiratory cycles. The rate of occurrence and characteristics of ABPs were not altered during a CO2 inhalation-induced hyperpnea. Pathological breathing patterns were eliminated during NREM sleep in 7 out of 8 goats, but they frequently occurred upon arousal from NREM sleep. We conclude that a moderate reduction in pre-BotzC NK1R-expressing neurons results in state-dependent transient changes in respiratory rhythm and/or eupneic respiratory muscle activation patterns.
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