Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
J Appl Physiol (1985). 2010 Jul;109(1):159-70. doi: 10.1152/japplphysiol.00933.2009. Epub 2010 Apr 29.
For many years, acetylcholine has been known to contribute to the control of breathing and sleep. To probe further the contributions of cholinergic rostral pontine systems in control of breathing, we designed this study to test the hypothesis that microdialysis (MD) of the muscarinic receptor antagonist atropine into the pontine respiratory group (PRG) would decrease breathing more in animals while awake than while in NREM sleep. In 16 goats, cannulas were bilaterally implanted into rostral pontine tegmental nuclei (n = 3), the lateral (n = 3) or medial (n = 4) parabrachial nuclei, or the Kölliker-Fuse nucleus (KFN; n = 6). After >2 wk of recovery from surgery, the goats were studied during a 45-min period of MD with mock cerebrospinal fluid (mCSF), followed by at least 30 min of recovery and a second 45-min period of MD with atropine. Unilateral and bilateral MD studies were completed during the day and at night. MD of atropine into the KFN at night decreased pulmonary ventilation and breathing frequency and increased inspiratory and expiratory time by 12-14% during both wakefulness and NREM sleep. However, during daytime studies, MD of atropine into the KFN had no effect on these variables. Unilateral and bilateral nighttime MD of atropine into the KFN increased levels of NREM sleep by 63 and 365%, respectively. MD during the day or at night into the other three pontine sites had minimal effects on any variable studied. Finally, compared with MD of mCSF, bilateral MD of atropine decreased levels of acetylcholine and choline in the effluent dialysis fluid. Our data support the concept that the KFN is a significant contributor to cholinergically modulated control of breathing and sleep.
多年来,乙酰胆碱一直被认为有助于控制呼吸和睡眠。为了进一步探究胆碱能桥脑前区系统在呼吸控制中的作用,我们设计了这项研究来检验这样一个假设,即通过微透析(MD)将毒蕈碱受体拮抗剂阿托品注入桥脑呼吸区(PRG),会使动物在清醒时比在非快速动眼睡眠(NREM)时呼吸更受抑制。在 16 只山羊中,双侧导管被植入桥脑被盖网状核(n = 3)、外侧(n = 3)或内侧(n = 4)臂旁核或 Kölliker-Fuse 核(KFN;n = 6)。在手术后>2 周的恢复后,山羊在 45 分钟的 MD 期间接受模拟脑脊液(mCSF),然后至少恢复 30 分钟,接着进行第二次 45 分钟的 MD 期间给予阿托品。单侧和双侧 MD 研究分别在白天和夜间完成。夜间将阿托品 MD 到 KFN 会降低肺通气和呼吸频率,并使吸气和呼气时间增加 12-14%,无论是在清醒还是 NREM 睡眠期间。然而,在白天的研究中,将阿托品 MD 到 KFN 对这些变量没有影响。夜间单侧和双侧 MD 到 KFN 的阿托品增加了 NREM 睡眠的水平,分别增加了 63%和 365%。白天或夜间将阿托品 MD 到其他三个桥脑部位对任何研究变量的影响都很小。最后,与 mCSF 的 MD 相比,双侧 MD 的阿托品降低了流出透析液中的乙酰胆碱和胆碱水平。我们的数据支持这样一个概念,即 KFN 是胆碱能调制呼吸和睡眠控制的重要贡献者。