Sleep and Serotonin Modulate Paracapsular Nitric Oxide Synthase Expressing Neurons of the Amygdala.
Sleep and Serotonin Modulate Paracapsular Nitric Oxide Synthase Expressing Neurons of the Amygdala.
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DOI：
10.1523/eneuro.0177-16.2016
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发表时间：
2016-09
期刊：
影响因子：
3.4
通讯作者：
Capogna M
中科院分区：
文献类型：
--
作者：
Bocchio M;Fisher SP;Unal G;Ellender TJ;Vyazovskiy VV;Capogna M
揭示不同神经元类型的作用是理解健康和疾病中的大脑功能的基本挑战。在调节情绪行为的大脑结构杏仁核中，gaba能神经元的多样性仅被部分探索。我们报道了一种表达高水平神经元一氧化氮合酶（nNOS）的新型gaba能杏仁核神经元群体。这些细胞主要分布在杏仁核基底外侧（BLA）边界。对Nos1-CreER的nNOS+神经元进行离体膜片钳记录；在Ai9小鼠中，我们观察到沿外囊分布的nNOS+神经元表现出独特的电生理特性、轴突和树突树突化和连通性。通过检测它们的c-Fos表达，我们发现囊旁nNOS+神经元在睡眠剥夺后的一段不受干扰的睡眠期间被激活，但在睡眠剥夺期间没有被激活。一致地，我们发现背中缝血清素[5-羟色胺（5-HT）]神经元参与睡眠-觉醒调节，支配nNOS+神经元。5-羟色胺通过5-HT1A受体使nNOS+神经元超极化。这种超极化导致放电速率降低，偶尔从强直放电模式切换到突发放电模式，从而与迄今为止报道的5-HT对BLA gaba能细胞的经典去极化作用形成对比。因此，nNOS+细胞是一种独特的杏仁核细胞类型，它以一种警惕状态依赖的方式控制杏仁核和杏仁核外区域下游神经元的活动。鉴于情绪、睡眠剥夺和5-羟色胺之间的密切联系，高睡眠压力后囊旁nNOS+神经元的募集可能是情绪调节的重要机制。
Unraveling the roles of distinct neuron types is a fundamental challenge to understanding brain function in health and disease. In the amygdala, a brain structure regulating emotional behavior, the diversity of GABAergic neurons has been only partially explored. We report a novel population of GABAergic amygdala neurons expressing high levels of neuronal nitric oxide synthase (nNOS). These cells are predominantly localized along basolateral amygdala (BLA) boundaries. Performing ex vivo patch-clamp recordings from nNOS+ neurons in Nos1-CreER;Ai9 mice, we observed that nNOS+ neurons located along the external capsule display distinctive electrophysiological properties, axonal and dendritic arborization, and connectivity. Examining their c-Fos expression, we found that paracapsular nNOS+ neurons are activated during a period of undisturbed sleep following sleep deprivation, but not during sleep deprivation. Consistently, we found that dorsal raphe serotonin [5-hydroxytryptamine (5-HT)] neurons, which are involved in sleep–wake regulation, innervate nNOS+ neurons. Bath application of 5-HT hyperpolarizes nNOS+ neurons via 5-HT1A receptors. This hyperpolarization produces a reduction in firing rate and, occasionally, a switch from tonic to burst firing mode, thereby contrasting with the classic depolarizing effect of 5-HT on BLA GABAergic cells reported so far. Thus, nNOS+ cells are a distinct cell type of the amygdala that controls the activity of downstream neurons in both amygdaloid and extra-amygdaloid regions in a vigilance state-dependent fashion. Given the strong links among mood, sleep deprivation, and 5-HT, the recruitment of paracapsular nNOS+ neurons following high sleep pressure may represent an important mechanism in emotional regulation.