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Sleep Regulation by Neurotensinergic Neurons in a Thalamo-Amygdala Circuit

机译:在Thalamo-Amygdala电路中由神经调度症神经元的睡眠调节

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摘要

A crucial step in understanding the sleep-control mechanismis to identify sleep neurons. Through systematic anatomical screening followed by functional testing, we identified two sleep-promoting neuronal populations along a thalamo-amygdala pathway, both expressing neurotensin (NTS). Rabies-mediated monosynaptic retrograde tracing identified the central nucleus of amygdala (CeA) as a major source of GABAergic inputs to multiple wake-promoting populations; gene profiling revealed NTS as a prominent marker for these CeA neurons. Optogenetic activation and inactivation of NTS-expressing CeA neurons promoted and suppressed non-REM (NREM) sleep, respectively, and optrode recording showed they are sleep active. Further tracing showed that CeA GABAergic NTS neurons are innervated by glutamatergic NTS neurons in a posterior thalamic region, which also promote NREM sleep. CRISPR/Cas9-mediated NTS knockdown in either the thalamic or CeA neurons greatly reduced their sleep-promoting effect. These results reveal a novel thalamo-amygdala circuit for sleep generation in which NTS signaling is essential for both the upstream glutamatergic and downstream GABAergic neurons.
机译:理解睡眠控制机制识别睡眠神经元的关键步骤。通过系统解剖学筛选,随后具有功能性测试,我们鉴定了沿着Thalamo-Amygdala途径的两种睡眠神经元群,两种嗜睡症(NTS)两种术语。狂犬病介导的单腹逆行描绘追踪鉴定了Amygdala(CEA)的中央核,作为多重唤醒群体的甘蓝输入的主要来源;基因分析显示NTS作为这些CEA神经元的突出标记。分别促进和抑制非REM(NREM)睡眠的NTS表达CEA神经元的致敏活化和失活,并且Optrode记录显示它们是睡眠活性的。进一步的追踪表明,CEA Gabaergic NTS神经元在后部丘脑区域中的谷氨酸NTS神经元接头,这也促进了NREM睡眠。 CRISPR / CAS9介导的NTS在丘脑或CEA神经元中敲低,大大降低了促进睡眠效果。这些结果揭示了一种用于睡眠发电的新型丘脑-Amygdala电路,其中NTS信令对于上游谷氨酸和下游胃肠杆菌神经元是必不可少的。

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  • 来源
    《Neuron》 |2019年第2期|共19页
  • 作者单位

    Univ Calif Berkeley Howard Hughes Med Inst Div Neurobiol Dept Mol &

    Cell Biol Helen Wills;

    Univ Calif Berkeley Howard Hughes Med Inst Div Neurobiol Dept Mol &

    Cell Biol Helen Wills;

    Univ Calif Berkeley Howard Hughes Med Inst Div Neurobiol Dept Mol &

    Cell Biol Helen Wills;

    Univ Calif Berkeley Howard Hughes Med Inst Div Neurobiol Dept Mol &

    Cell Biol Helen Wills;

    Univ Calif San Francisco Dept Neurol Eli &

    Edythe Broad Ctr Regenerat Med &

    Stem Cell San;

    Univ Calif Berkeley Howard Hughes Med Inst Div Neurobiol Dept Mol &

    Cell Biol Helen Wills;

    Univ Calif Berkeley Howard Hughes Med Inst Div Neurobiol Dept Mol &

    Cell Biol Helen Wills;

    Univ Calif Berkeley Howard Hughes Med Inst Div Neurobiol Dept Mol &

    Cell Biol Helen Wills;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

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