Basal forebrain control of wakefulness and cortical rhythms.
Basal forebrain control of wakefulness and cortical rhythms.
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DOI：
10.1038/ncomms9744
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发表时间：
2015-11-03
影响因子：
16.6
通讯作者：
Fuller PM
中科院分区：
文献类型：
--
作者：
Anaclet C;Pedersen NP;Ferrari LL;Venner A;Bass CE;Arrigoni E;Fuller PM
清醒、沿着快速皮质节律和相关认知，取决于基底前脑（BF）。痴呆症中BF胆碱能细胞的损失和抗胆碱能药物的镇静作用长期以来一直暗示这些神经元对认知和觉醒很重要。BF还含有混合的抑制性GABA能和兴奋性GABA能细胞群，其确切的神经生物学作用尚不清楚。在这里，我们表明，遗传靶向化学激活BF胆碱能或神经元的行为小鼠产生显着影响的状态巩固和/或脑电图，但总唤醒没有影响。BF GABA能神经元的类似激活产生持续的觉醒和高频皮质节律，而化学发生抑制增加睡眠。我们的研究结果揭示了BF GABA能神经元对觉醒和与认知相关的快速皮质节律的主要贡献。这些发现可能是临床上适用于旨在增加前脑激活痴呆症和最低意识状态的操作。 哺乳动物的基底前脑控制皮质节律和觉醒-睡眠。Anaclet等人使用遗传靶向化学遗传学系统来激活或抑制该区域的胆碱能、谷氨酸能或GABA能神经元，并揭示它们对行为小鼠的行为和皮质电唤醒的贡献。
Wakefulness, along with fast cortical rhythms and associated cognition, depend on the basal forebrain (BF). BF cholinergic cell loss in dementia and the sedative effect of anti-cholinergic drugs have long implicated these neurons as important for cognition and wakefulness. The BF also contains intermingled inhibitory GABAergic and excitatory glutamatergic cell groups whose exact neurobiological roles are unclear. Here we show that genetically targeted chemogenetic activation of BF cholinergic or glutamatergic neurons in behaving mice produced significant effects on state consolidation and/or the electroencephalogram but had no effect on total wake. Similar activation of BF GABAergic neurons produced sustained wakefulness and high-frequency cortical rhythms, whereas chemogenetic inhibition increased sleep. Our findings reveal a major contribution of BF GABAergic neurons to wakefulness and the fast cortical rhythms associated with cognition. These findings may be clinically applicable to manipulations aimed at increasing forebrain activation in dementia and the minimally conscious state. The mammalian basal forebrain controls cortical rhythm and wake-sleep. Anaclet et al. use genetically-targeted chemogenetic systems to activate or inhibit cholinergic, glutamatergic or GABAergic neurons in this region, and reveal their contributions to behavioral and electrocortical arousal in behaving mice.