Anaclet Christelle, Ferrari Loris, Arrigoni Elda, Bass Caroline E, Saper Clifford B, Lu Jun, Fuller Patrick M
Department of Neurology, Division of Sleep Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
Nat Neurosci. 2014 Sep;17(9):1217-24. doi: 10.1038/nn.3789. Epub 2014 Aug 17.
Work in animals and humans has suggested the existence of a slow wave sleep (SWS)-promoting/electroencephalogram (EEG)-synchronizing center in the mammalian lower brainstem. Although sleep-active GABAergic neurons in the medullary parafacial zone (PZ) are needed for normal SWS, it remains unclear whether these neurons can initiate and maintain SWS or EEG slow-wave activity (SWA) in behaving mice. We used genetically targeted activation and optogenetically based mapping to examine the downstream circuitry engaged by SWS-promoting PZ neurons, and we found that this circuit uniquely and potently initiated SWS and EEG SWA, regardless of the time of day. PZ neurons monosynaptically innervated and released synaptic GABA onto parabrachial neurons, which in turn projected to and released synaptic glutamate onto cortically projecting neurons of the magnocellular basal forebrain; thus, there is a circuit substrate through which GABAergic PZ neurons can potently trigger SWS and modulate the cortical EEG.
对动物和人类的研究表明,哺乳动物的低位脑干中存在促进慢波睡眠(SWS)/同步脑电图(EEG)的中枢。虽然延髓旁面部区(PZ)中具有睡眠激活作用的γ-氨基丁酸能(GABAergic)神经元对正常的慢波睡眠是必需的,但尚不清楚这些神经元是否能在行为小鼠中启动并维持慢波睡眠或脑电图慢波活动(SWA)。我们利用基因靶向激活和基于光遗传学的图谱分析来研究促进慢波睡眠的PZ神经元所涉及的下游神经回路,并且我们发现,无论在一天中的什么时间,该神经回路都能独特且有效地启动慢波睡眠和脑电图慢波活动。PZ神经元通过单突触支配臂旁神经元并向其释放突触GABA,而臂旁神经元又转而投射到巨细胞基底前脑的皮质投射神经元并向其释放突触谷氨酸;因此,存在一个神经回路基质,通过该基质,GABA能PZ神经元可以有效地触发慢波睡眠并调节皮质脑电图。