Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
J Neurosci. 2012 Feb 1;32(5):1622-33. doi: 10.1523/JNEUROSCI.5700-10.2012.
Serotonin type 1A (5-HT(1A)) receptor-responsive neurons in the pedunculopontine tegmental nucleus (PPTn) become maximally active immediately before and during rapid eye movement (REM) sleep. A prevailing model of REM sleep generation indicates that activation of such neurons contributes significantly to the generation of REM sleep, and if correct then inactivation of such neurons ought to suppress REM sleep. We test this hypothesis using bilateral microperfusion of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 μm) into the PPTn; this tool has been shown to selectively silence REM sleep-active PPTn neurons while the activity of wake/REM sleep-active PPTn neurons is unaffected. Contrary to the prevailing model, bilateral microperfusion of 8-OH-DPAT into the PPTn (n = 23 rats) significantly increased REM sleep both as a percentage of the total recording time and sleep time, compared with both within-animal vehicle controls and between-animal time-controls. This increased REM sleep resulted from an increased frequency of REM sleep bouts but not their duration, indicating an effect on mechanisms of REM sleep initiation but not maintenance. Furthermore, an increased proportion of the REM sleep bouts stemmed from periods of low REM sleep drive quantified electrographically. Targeted suppression of 5-HT(1A) receptor-responsive PPTn neurons also increased respiratory rate and respiratory-related genioglossus activity, and increased the frequency and amplitude of the sporadic genioglossus activations occurring during REM sleep. These data indicate that 5-HT(1A) receptor-responsive PPTn neurons normally function to restrain REM sleep by elevating the drive threshold for REM sleep induction, and restrain the expression of respiratory rate and motor activities.
5-羟色胺 1A（5-HT1A）受体反应性神经元在脚桥被盖核（PPTn）中在快速眼动（REM）睡眠之前和期间变得最大程度活跃。一种流行的 REM 睡眠产生模型表明，这种神经元的激活对 REM 睡眠的产生有重要贡献，如果正确的话，那么这种神经元的失活应该会抑制 REM 睡眠。我们使用双侧微量灌流 5-HT1A 受体激动剂 8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT，10μm）到 PPTn 中测试了这一假说；该工具已被证明可以选择性地沉默 REM 睡眠活性 PPTn 神经元，而觉醒/REM 睡眠活性 PPTn 神经元的活性不受影响。与流行模型相反，双侧微量灌流 8-OH-DPAT 到 PPTn（n=23 只大鼠）显著增加了 REM 睡眠，无论是在总记录时间还是睡眠时间的百分比上，与动物自身的对照和动物之间的时间对照相比都是如此。这种 REM 睡眠的增加是由于 REM 睡眠发作的频率增加而不是持续时间增加，表明对 REM 睡眠起始机制而不是维持机制的影响。此外，通过电描记法定量的 REM 睡眠驱动的低 REM 睡眠时期增加了 REM 睡眠发作的比例。靶向抑制 5-HT1A 受体反应性 PPTn 神经元也增加了呼吸频率和呼吸相关的颏舌肌活动，并增加了 REM 睡眠期间发生的偶发性颏舌肌激活的频率和幅度。这些数据表明，5-HT1A 受体反应性 PPTn 神经元通过提高 REM 睡眠诱导的驱动阈值来正常抑制 REM 睡眠，并抑制呼吸频率和运动活动的表达。
