Metabotropic Acetylcholine and Glutamate Receptors Mediate PI(4,5) P2 Depletion and Oscillations in Hippocampal CA1 Pyramidal Neurons in situ
Metabotropic Acetylcholine and Glutamate Receptors Mediate PI(4,5) P2 Depletion and Oscillations in Hippocampal CA1 Pyramidal Neurons in situ
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DOI：
10.1038/s41598-018-31322-8
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发表时间：
2018-08-28
影响因子：
4.6
通讯作者：
Oliver, Dominik
中科院分区：
文献类型：
--
作者：
Hackelberg, Sandra;Oliver, Dominik
许多离子通道对细胞膜中磷脂酰肌醇-4，5-二磷酸（PIP 2）水平的敏感性表明PIP 2波动是调节神经元兴奋性的重要和一般信号。然而，中枢神经元在其天然环境中的PIP 2动力学在很大程度上仍未被探索。在这里，我们研究了行为的PIP 2浓度响应于激活Gq偶联神经递质受体在大鼠海马CA 1区神经元原位急性脑切片。PIP 2选择性分子传感器tubby（CT）-GFP和PLC delta 1-PH-GFP的共聚焦显微镜显示，毒蕈碱乙酰胆碱（mAChR）或I组代谢型谷氨酸（mGluRI）受体的药理学激活诱导索马和树突树中PIP 2的瞬时消耗。所观察到的PIP 2动力学是受体特异性的，mAChR激活诱导的PIP 2消耗比mGluRI更强，而CA 1神经元中表达的其他G α（q）偶联受体的激动剂不会诱导可测量的PIP 2消耗。此外，数据首次显示了神经元受体诱导的膜PIP 2浓度振荡。振荡行为表明，神经元可以在Gq和PLC的持续激活期间快速恢复PIP 2水平。对受体激活的电生理反应在时间过程和受体特异性方面类似于PIP 2动力学。我们的研究结果支持PIP 2在调节电活动中的生理功能。
The sensitivity of many ion channels to phosphatidylinositol-4,5-bisphosphate (PIP2) levels in the cell membrane suggests that PIP2 fluctuations are important and general signals modulating neuronal excitability. Yet the PIP2 dynamics of central neurons in their native environment remained largely unexplored. Here, we examined the behavior of PIP2 concentrations in response to activation of Gq-coupled neurotransmitter receptors in rat CA1 hippocampal neurons in situ in acute brain slices. Confocal microscopy of the PIP2-selective molecular sensors tubby(CT)-GFP and PLC delta 1-PH-GFP showed that pharmacological activation of muscarinic acetylcholine (mAChR) or group I metabotropic glutamate (mGluRI) receptors induces transient depletion of PIP2 in the soma as well as in the dendritic tree. The observed PIP2 dynamics were receptor-specific, with mAChR activation inducing stronger PIP2 depletion than mGluRI, whereas agonists of other G alpha(q)-coupled receptors expressed in CA1 neurons did not induce measureable PIP2 depletion. Furthermore, the data show for the first time neuronal receptor-induced oscillations of membrane PIP2 concentrations. Oscillatory behavior indicated that neurons can rapidly restore PIP2 levels during persistent activation of Gq and PLC. Electrophysiological responses to receptor activation resembled PIP2 dynamics in terms of time course and receptor specificity. Our findings support a physiological function of PIP2 in regulating electrical activity.