Microdialysis (MD) of atropine into the Kölliker‐Fuse Nucleus (KFN) alters breathing of awake and sleeping goats

Abstract

We MD atropine, a muscarinic receptor antagonist, at sites in the rostral pons of awake and sleeping goats to test the hypothesis that cholinergic mechanisms have site‐ and state‐dependent effects on the control of breathing. Cannula were bilaterally implanted into either rostral pontine tegmental nuclei (n = 3), the lateral (n = 3) or medial (n = 4) parabrachial nuclei, or the KFN (n = 6). After >2 weeks recovery from surgery, the goats were studied during a 45 minute period of MD with mock cerebrospinal fluid, followed by 30 minutes of recovery and 45 minutes of MD with atropine. Unilateral and bilateral MD of atropine into the KFN at night decreased pulmonary ventilation and breathing frequency and increased inspiratory and expiratory time by 12 to 14% during both wakefulness and NREM sleep. However, during daytime studies, MD of atropine into the KFN had no affect on these variables but increased the variation of genioglossus muscle activity. Nighttime unilateral and bilateral MD of atropine into the KFN increased NREM sleep by 63% (p > 0.05) and 365% (p < 0.01), respectively. MD during the day or at night into the other 3 pontine sites had only minimal effects on any variable studied. Finally, bilateral MD of atropine decreased levels of acetylcholine and choline in the effluent dialysate. Our data support the concept that the KFN is a significant contributor to cholinergically modulated control of breathing and sleep.