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首页> 外文期刊>Neuron >Septal Cholinergic Neuromodulation Tunes the Astrocyte-Dependent Gating of Hippocampal NMDA Receptors to Wakefulness
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Septal Cholinergic Neuromodulation Tunes the Astrocyte-Dependent Gating of Hippocampal NMDA Receptors to Wakefulness

机译：隔膜胆碱能神经调节调整海马NMDA受体的星形胶质细胞依赖性术治疗觉醒

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摘要

The activation of the N-methyl D-aspartate receptor (NMDAR) is controlled by a glutamate-binding site and a distinct, independently regulated, co-agonistbinding site. In most brain regions, the NMDAR co-agonist is the astrocyte-derived gliotransmitter D-serine. We found that D-serine levels oscillate in mouse hippocampus as a function of wakefulness, in vitro and in vivo. This causes a full saturation of the NMDAR co-agonist site in the dark (active) phase that dissipates to sub-saturating levels during the light (sleep) phase, and influences learning performance throughout the day. We demonstrate that hippocampal astrocytes sense the wakefulness- dependent activity of septal cholinergic fibers through the alpha 7-nicotinic acetylcholine receptor (alpha 7nAChR), whose activation drives D-serine release. We conclude that astrocytes tune the gating of synapticNMDARs to the vigilance state anddemonstrate that this is directly relevant to schizophrenia, a disorder characterized by NMDAR and cholinergic hypofunctions. Indeed, bypassing cholinergic activity with a clinically tested alpha 7-nAChR agonist successfully enhances NMDAR activation.
机译：N-甲基D-天冬氨酸受体（NMDAR）的活化由谷氨酸结合位点和明显的独立调节的共激菌位点控制。在大多数大脑区域中，芽孢杆菌共激动剂是星形胶质细胞衍生的嗜慢的嗜胺。我们发现D-丝氨酸水平在小鼠海马中振荡，作为清醒，体外和体内的函数。这使得NMDAR共激动剂位点在暗（活性）相中的全饱和度，其在光（睡眠）相期间渗透到亚饱和水平，并影响全天的学习表现。我们证明海马星形胶质细胞通过α7-烟碱乙酰胆碱受体（α7NAChR）感知隔膜胆碱能纤维的醒来依赖性活性，其活化驱动D-丝氨酸释放。我们得出结论，星形胶质细胞调整Synapticnmdars对警惕状态的术语，并且这与精神分裂症直接相关，这种疾病是由NMDAR和胆碱能紊乱的紊乱。实际上，用临床测试的α7-NACHR激动剂绕过胆碱能活性，成功增强了NMDAR活化。

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  • 来源
    《Neuron》 |2017年第4期|共15页
  • 作者

    Papouin Thomas; Dunphy Jaclyn M.; Tolman Michaela; Dineley Kelly T.; Haydon Philip G.;

  • 作者单位

    Tufts Univ Sch Med Dept Neurosci Boston MA 02111 USA;

    Tufts Sackler Sch Grad Biomed Sci Neurosci Program Boston MA 02111 USA;

    Tufts Sackler Sch Grad Biomed Sci Neurosci Program Boston MA 02111 USA;

    Univ Texas Med Branch Dept Neurol Galveston TX 77555 USA;

    Tufts Univ Sch Med Dept Neurosci Boston MA 02111 USA;

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  • 正文语种 eng
  • 中图分类 神经病学;
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