An excitatory peri-tegmental reticular nucleus circuit for wake maintenance.
An excitatory peri-tegmental reticular nucleus circuit for wake maintenance.
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DOI：
10.1073/pnas.2203266119
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发表时间：
2022-08-23
影响因子：
11.1
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中科院分区：
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虽然许多大脑区域已被证明参与使用模式生物的睡眠-觉醒调节，我们试图确定一个区域相关的人类睡眠时间调节。我们从人类睡眠持续时间基因（ADRB 1）出发，然后使用无偏的方法来鉴定被盖周围网状核（pTRNADB 1）作为参与睡眠-觉醒调节的区域。我们发现，pTRNADB 1神经元是唤醒活性的，是觉醒的有效促进者，它们的激活在刺激结束后促进觉醒。此外，组合遗传学显示，兴奋性pTRNADB 1神经元主要负责这种表型，它们通过投射到外侧下丘脑部分发挥作用。因此，pTRN在睡眠-觉醒调节中起重要作用。睡眠是我们生存的必需品，但它的调节仍然不完全清楚。在这里，我们使用人类睡眠持续时间基因来识别被盖周围网状核（pTRNADB 1）中调节睡眠-觉醒的细胞群，揭示了一个知之甚少的大脑区域的作用。尽管小鼠中的初始消融导致觉醒增加，但进一步验证显示，pTRNADB 1神经元刺激强烈促进觉醒，即使在刺激抵消后。使用组合遗传学，我们发现兴奋性pTRNADB 1神经元促进觉醒。pTRN神经元可基于测序投射的多重分析（MAPseq）分析表征为前投射神经元或后投射神经元。最后，我们发现pTRNADB 1神经元促进觉醒，部分是通过投射到外侧下丘脑。因此，来自人类睡眠特征的人类遗传信息使我们能够确定pTRN在睡眠-觉醒调节中的作用。
Although many brain regions have been shown to participate in sleep–wake regulation using model organisms, we sought to identify a region relevant to human sleep duration regulation. We started from a human sleep duration gene (ADRB1) and then used an unbiased approach to identify the peri-tegmental reticular nucleus (pTRNADRB1) as a region participating in sleep–wake regulation. We found that pTRNADRB1 neurons are wake-active and are potent promoters of wakefulness, with their activation promoting wakefulness well after the end of stimulation. Further, combinatorial genetics revealed that excitatory pTRNADRB1 neurons are primarily responsible for this phenotype and that they act in part through projections to the lateral hypothalamus. Thus, the pTRN plays an important role in sleep–wake regulation. Sleep is a necessity for our survival, but its regulation remains incompletely understood. Here, we used a human sleep duration gene to identify a population of cells in the peri-tegmental reticular nucleus (pTRNADRB1) that regulate sleep–wake, uncovering a role for a poorly understood brain area. Although initial ablation in mice led to increased wakefulness, further validation revealed that pTRNADRB1 neuron stimulation strongly promotes wakefulness, even after stimulation offset. Using combinatorial genetics, we found that excitatory pTRNADRB1 neurons promote wakefulness. pTRN neurons can be characterized as anterior- or posterior-projecting neurons based on multiplexed analysis of projections by sequencing (MAPseq) analysis. Finally, we found that pTRNADRB1 neurons promote wakefulness, in part, through projections to the lateral hypothalamus. Thus, human genetic information from a human sleep trait allowed us to identify a role for the pTRN in sleep–wake regulation.
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