Alterations of the electrophysiological properties from cortical layer 5 pyramidal neurons in temporary rapamycin-treated rodent brain slices
Alterations of the electrophysiological properties from cortical layer 5 pyramidal neurons in temporary rapamycin-treated rodent brain slices
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临时雷帕霉素处理的啮齿动物脑切片中皮质第 5 层锥体神经元电生理特性的变化
DOI：
10.1016/j.neulet.2015.11.039
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发表时间：
2016-01
影响因子：
2.5
通讯作者：
Kewen Jiang
中科院分区：
文献类型：
--
作者：
Keming Ren;Lijuan Chen;Guoxia Sheng;Jiangping Wang;Xiaoming Jin;Kewen Jiang
哺乳动物雷帕霉素靶蛋白（mTOR）信号通路参与神经发育/变性和神经精神异常。雷帕霉素是一种特异性的mTOR信号抑制剂，可调节长时间处理后的突触可塑性和突触传递。其对皮层第5层（L5）锥体神经元的电生理特性的直接影响，其中信息经历复杂的处理仍然未知。在此，我们发现急性（2分钟内）浴用雷帕霉素（0.5 μg ml−1）能够显著降低出生后第4天（P）、大鼠P10和小鼠P90的电流钳基线电位（P< 0.05），并以年龄依赖性方式改变膜电流/电压（I/V）曲线。雷帕霉素不仅增加了基线膜电位的标准差或峰值幅度，而且增加了更成熟神经元（P10和P90）的自发动作电位频率。此外，雷帕霉素降低了成熟大脑皮层L5爆发-尖峰神经元的爆发-放电频率，并进一步将其放电模式转换为常规-尖峰模式。这些结果表明雷帕霉素对mTOR信号的急性抑制对L5锥体神经元的电生理特性产生了直接影响，表明其作用可能涉及离子通道的调节机制。
The mammalian target of rapamycin (mTOR) signaling pathway is involved in neuro-developmental/degenerative and neuropsychiatric abnormalities. Rapamycin, a specific and potent inhibitor of mTOR signaling, could regulate synaptic plasticity and synaptic transmission of glutamatergic neurons following prolonged treatment. Its immediate effects on electrophysiological properties of cortical layer 5 (L5) pyramidal neurons where the information undergoes a sophisticated processing remain unknown. Here, we found that acute (within 2 min) bath-application of rapamycin (0.5 μg ml−1) was able to depolarize the current-clamp baseline potentials significantly at postnatal day (P) 4, P10 in rats and P90 in mice (P< 0.05), and altered the membrane current/voltage (I/V) curves in an age-dependent manner. Rapamycin not only increased the standard deviation or the peak amplitude of baseline membrane potential, but also increased the frequencies of spontaneous action potentials in more mature neurons (P10 and P90). In addition, rapamycin decreased the burst-firing frequencies of cortical L5 burst-spiking neurons from mature brains, and further switched their firing modes to regular-spiking ones. These findings suggest that acute inhibition of mTOR signaling by rapamycin induces an immediate impact on L5 pyramidal neurons’ electrophysiological properties, indicating that its effects might involve mechanisms of ion channel’s regulation.
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影响因子：
2.9
作者：
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