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睡眠驱动力会重新配置促进清醒的时钟电路,以调节适应性行为。

Sleep drive reconfigures wake-promoting clock circuitry to regulate adaptive behavior.

作者信息

Klose Markus K, Shaw Paul J

机构信息

Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri, United States of America.

出版信息

PLoS Biol. 2021 Jun 30;19(6):e3001324. doi: 10.1371/journal.pbio.3001324. eCollection 2021 Jun.

DOI:10.1371/journal.pbio.3001324
PMID:34191802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8277072/
Abstract

Circadian rhythms help animals synchronize motivated behaviors to match environmental demands. Recent evidence indicates that clock neurons influence the timing of behavior by differentially altering the activity of a distributed network of downstream neurons. Downstream circuits can be remodeled by Hebbian plasticity, synaptic scaling, and, under some circumstances, activity-dependent addition of cell surface receptors; the role of this receptor respecification phenomena is not well studied. We demonstrate that high sleep pressure quickly reprograms the wake-promoting large ventrolateral clock neurons to express the pigment dispersing factor receptor (PDFR). The addition of this signaling input into the circuit is associated with increased waking and early mating success. The respecification of PDFR in both young and adult large ventrolateral neurons requires 2 dopamine (DA) receptors and activation of the transcriptional regulator nejire (cAMP response element-binding protein [CREBBP]). These data identify receptor respecification as an important mechanism to sculpt circuit function to match sleep levels with demand.

摘要

昼夜节律有助于动物使动机性行为同步,以适应环境需求。最近的证据表明,生物钟神经元通过差异性地改变下游神经元分布式网络的活动来影响行为的时间安排。下游回路可通过赫布可塑性、突触缩放以及在某些情况下通过依赖活动的细胞表面受体添加来重塑;这种受体重新指定现象的作用尚未得到充分研究。我们证明,高睡眠压力会迅速重新编程促进觉醒的大腹外侧生物钟神经元,使其表达色素分散因子受体(PDFR)。将这种信号输入添加到回路中与觉醒增加和早期交配成功相关。在幼年和成年大腹外侧神经元中,PDFR的重新指定需要2种多巴胺(DA)受体以及转录调节因子nejire(环磷酸腺苷反应元件结合蛋白[CREBBP])的激活。这些数据表明受体重新指定是塑造回路功能以使睡眠水平与需求相匹配的重要机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/8277072/e23c74bd6e35/pbio.3001324.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/8277072/a48a784eba75/pbio.3001324.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/8277072/e23c74bd6e35/pbio.3001324.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/8277072/a48a784eba75/pbio.3001324.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/8277072/1e15359b7ce0/pbio.3001324.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/8277072/4993f220fa45/pbio.3001324.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/8277072/16165ee71a34/pbio.3001324.g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/8277072/e23c74bd6e35/pbio.3001324.g006.jpg

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Neuron-specific knockouts indicate the importance of network communication to rhythmicity.神经元特异性敲除表明网络通讯对节律性的重要性。
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Dissection of central clock function in through cell-specific CRISPR-mediated clock gene disruption.通过细胞特异性 CRISPR 介导的时钟基因敲除来剖析中枢时钟功能。
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Sleep-promoting neurons remodel their response properties to calibrate sleep drive with environmental demands.促进睡眠的神经元重塑其反应特性,以根据环境需求调整睡眠驱动力。
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