Lanir-Azaria Sa'ar, Meiri Guy, Avigdor Tamir, Minert Anne, Devor Marshall
Department of Cell and Developmental Biology, Institute of Life Sciences and Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Department of Cell and Developmental Biology, Institute of Life Sciences and Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Behav Brain Res. 2018 Apr 2;341:198-211. doi: 10.1016/j.bbr.2017.12.035. Epub 2017 Dec 27.
The induction of general anesthesia shares many features with the transition from wakefulness to non-rapid eye movement (NREM) sleep, suggesting that the two types of brain-state transition are orchestrated by a common neuronal mechanism. Previous studies revealed a brainstem locus, the mesopontine tegmental anesthesia area (MPTA), that is of singular importance for anesthetic induction. Microinjection of GABAergic anesthetics there induces rapid loss-of-consciousness and lesions render the animal relatively insensitive to anesthetics administered systemically. Here we show that MPTA lesions also alter the natural sleep-wake rhythm by increasing overall wake time at the expense of time asleep (NREM and REM sleep equally), with nearly all of the change occurring during the dark hours of the light-dark cycle. The effect was proportional to the extent of the lesion and was not seen after lesions just outside of the MPTA, or following sham lesions. Thus, MPTA neurons appear to play a role in natural bistable brain-state switching (sleep-wake) as well as in loss and recovery of consciousness induced pharmacologically.
全身麻醉的诱导与从清醒状态转变为非快速眼动（NREM）睡眠有许多共同特征，这表明这两种脑状态转变是由一种共同的神经元机制协调的。先前的研究揭示了一个脑干位点，即中脑桥脑被盖麻醉区（MPTA），它对麻醉诱导具有独特的重要性。在此处进行GABA能麻醉剂的微量注射会导致快速意识丧失，而损伤该区域会使动物对全身给药的麻醉剂相对不敏感。我们在此表明，MPTA损伤还会改变自然睡眠-觉醒节律，以睡眠时间（NREM睡眠和快速眼动睡眠减少程度相同）为代价增加总体清醒时间，几乎所有变化都发生在明暗周期的黑暗时段。这种效应与损伤程度成正比，在MPTA之外的区域进行损伤后或假损伤后未观察到这种效应。因此，MPTA神经元似乎在自然双稳态脑状态转换（睡眠-觉醒）以及药理学诱导的意识丧失和恢复中发挥作用。
