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首页> 外文期刊>The European Journal of Neuroscience >Activation of nicotinic acetylcholine receptors enhances a slow calcium-dependent potassium conductance and reduces the firing of stratum oriens interneurons.
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Activation of nicotinic acetylcholine receptors enhances a slow calcium-dependent potassium conductance and reduces the firing of stratum oriens interneurons.

机译:烟碱乙酰胆碱受体的激活增强了钙依赖性钾电导的慢度,并降低了中层神经元的放电。

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摘要

A large variety of distinct locally connected GABAergic cells are present in the hippocampus. By releasing GABA into principal cells and interneurons, they exert a powerful control on neuronal excitability and are responsible for network oscillations crucial for information processing in the brain. Here, whole-cell patch clamp recordings in current and voltage clamp mode were used to study the functional role of nicotinic acetylcholine receptors (nAChRs) on the firing properties of stratum oriens interneurons in hippocampal slices from transgenic mice expressing enhanced green fluorescent protein in a subpopulation of GABAergic cells containing somatostatin (GIN mice). Unexpectedly, activation of nAChRs by nicotine or endogenously released acetylcholine strongly enhanced spike frequency adaptation. This effect was blocked by apamin, suggesting the involvement of small calcium-dependent potassium channels (SK channels). Nicotine-induced reduction in firing frequency was dependent on intracellular calcium rise through calcium-permeable nAChRs and voltage-dependent calcium channels activated by the depolarizing action of nicotine. Calcium imaging experiments directly showed that nicotine effects on firing rate were correlated with large increases in intracellular calcium. Furthermore, blocking ryanodine receptors with ryanodine or sarcoplasmic-endoplasmic reticulum calcium ATPase with thapsygargin or cyclopiazonic acid fully prevented the effects of nicotine, suggesting that mobilization of calcium from the internal stores contributed to the observed effects. By regulating cell firing, cholinergic signalling through nAChRs would be instrumental for fine-tuning the output of stratum oriens interneurons and correlated activity at the network level.
机译:海马中存在大量不同的局部连接的GABA能细胞。通过将GABA释放到主要细胞和中间神经元中,它们对神经元兴奋性发挥了强大的控制作用,并负责网络振荡,这对于大脑中的信息处理至关重要。在这里,以电流和电压钳模式的全细胞膜片钳记录来研究烟碱乙酰胆碱受体(nAChRs)对海马切片中海马层中层神经元的放电特性的功能作用,该海马切片来自在亚群中表达增强的绿色荧光蛋白的转基因小鼠。含有生长抑素的GABA能细胞(GIN小鼠)。出乎意料的是,尼古丁或内源性释放的乙酰胆碱对nAChRs的激活强烈增强了刺突频率适应性。 apapamin阻断了这种作用,提示参与了钙依赖性小钾通道(SK通道)。尼古丁引起的放电频率降低取决于通过钙可渗透的nAChRs引起的细胞内钙升高和尼古丁去极化作用激活的电压依赖性钙通道。钙成像实验直接表明,尼古丁对射击速率的影响与细胞内钙的大量增加有关。此外,用雷诺他定或肌浆网状内质网钙ATP酶和thapsygargin或环吡唑酸来阻断莱诺碱受体,可以完全阻止尼古丁的作用,这表明从内部储存中调动钙有助于观察到作用。通过调节细胞的放电,通过nAChRs产生的胆碱能信号将有助于微调层间神经元的输出以及在网络水平上的相关活性。

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