Astrocytic GABA transporter controls sleep by modulating GABAergic signaling in Drosophila circadian neurons.
Astrocytic GABA transporter controls sleep by modulating GABAergic signaling in Drosophila circadian neurons.
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DOI：
10.1016/j.cub.2022.02.066
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发表时间：
2022-05-09
期刊：
影响因子：
9.2
通讯作者：
Emery, Patrick
中科院分区：
文献类型：
--
作者：
Chaturvedi, Ratna;Stork, Tobias;Yuan, Chunyan;Freeman, Marc R.;Emery, Patrick
睡眠和清醒之间的精确平衡对于维持良好的生活质量和最佳的大脑功能至关重要。众所周知，GABA在睡眠控制中起着关键和保守的作用，因此GABA能张力应该在睡眠回路中受到严格控制。在这里，我们研究了星形细胞GABA转运体（GAT）在果蝇睡眠调节中的作用。我们发现，半胚性gat突变（gat33-1）增加了睡眠量，减少了睡眠潜伏期，并增加了夜间睡眠巩固。有趣的是，当gat33-1与破坏宽醒（wake）的突变结合时，睡眠缺陷被抑制，宽醒（wake）是一种调节GABAA受体细胞表面水平的基因，该受体在促进清醒的大腹侧神经元（l-LNvs）中抵抗狄氏（RDL）。此外，RNAi敲低这些昼夜神经元中的rdl及其调节剂dnlg4和wake也抑制了gat33-1睡眠表型。脑免疫组化显示，表达gat的星形胶质细胞位于rdl阳性的l-LNvs细胞体和树突附近。我们认为，星形细胞GAT降低了gaba能张力和RDL激活，从而促进了LNvs的觉醒，从而决定了果蝇适当的睡眠量和质量。睡眠是保守的，对健康和生存至关重要。GABA是促进睡眠的主要抑制性神经递质。Chaturvedi等人表明，在果蝇中，星形细胞GABA转运体GAT通过降低促进觉醒的昼夜节律神经元上的GABA张力来控制睡眠。因此，他们的研究揭示了一种调节睡眠的新机制。
A precise balance between sleep and wakefulness is essential to sustain a good quality of life and optimal brain function. GABA is known to play a key and conserved role in sleep control, and GABAergic tone should therefore be tightly controlled in sleep circuits. Here we examined the role of the astrocytic GABA transporter (GAT) in sleep regulation using Drosophila melanogaster. We found that a hypomorphic gat mutation (gat33-1) increased sleep amount, decreased sleep latency, and increased sleep consolidation at night. Interestingly, sleep defects were suppressed when gat33-1 was combined with a mutation disrupting wide-awake (wake), a gene that regulates the cell-surface levels of the GABAA receptor Resistance to Dieldrin (RDL) in the wake-promoting large ventral lateral neurons (l-LNvs). Moreover, RNAi knockdown of rdl and its modulators dnlg4 and wake in these circadian neurons also suppressed gat33-1 sleep phenotypes. Brain immunohistochemistry showed that GAT-expressing astrocytes were located near RDL-positive l-LNvs cell bodies and dendritic processes. We conclude that astrocytic GAT decreases GABAergic tone and RDL activation in arousal promoting LNvs, thus determining proper sleep amount and quality in Drosophila. Sleep is conserved and critical for good health and survival. GABA is the main inhibitory neurotransmitter promoting sleep. Chaturvedi et al. show that in Drosophila, the astrocytic GABA transporter GAT controls sleep by reducing GABA tone on arousal-promoting circadian neurons. Their work thus reveals a novel mechanism that modulates sleep.
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影响因子：
--
作者：
Jackson FR;Ng FS;Sengupta S;You S;Huang Y
通讯作者：
Huang Y
影响因子：
3.7
作者：
Donelson NC;Kim EZ;Slawson JB;Vecsey CG;Huber R;Griffith LC
通讯作者：
Griffith LC
影响因子：
64.8
作者：
Grima, B;Chèlot, E;Rouyer, F
通讯作者：
Rouyer, F
星形胶质细胞和睡眠的调节。
影响因子：
5.7
作者：
Haydon PG
通讯作者：
Haydon PG
DOI：
10.1016/j.cub.2020.10.012
发表时间：
2021-01-11
期刊：
Current biology : CB
影响因子：
--
作者：
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通讯作者：
Wu MN