NMDA Receptors Amplify Mossy Fiber Synaptic Inputs at Frequencies up to at Least 750 Hz in Cerebellar Granule Cells
NMDA Receptors Amplify Mossy Fiber Synaptic Inputs at Frequencies up to at Least 750 Hz in Cerebellar Granule Cells
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DOI：
10.1002/syn.21898
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发表时间：
2016-07-01
期刊：
影响因子：
2.3
通讯作者：
Hallermann, Stefan
中科院分区：
文献类型：
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作者：
Baade, Carolin;Byczkowicz, Niklas;Hallermann, Stefan
高频信号的神经元整合对于快速信息处理是重要的。小脑苔藓纤维轴突（MF）可以在超过一千赫兹的频率下激发动作电位（AP）。然而，目前还不清楚是否以及如何突触后小脑颗粒细胞（GC）能够处理这些高频MF输入。在这里，我们测量AP发射GC在高频MF刺激，并显示GC的发射频率增加非线性时，MF刺激频率从100到750 Hz。为了研究实现这种高频信号的机制，我们分析了N-甲基-D-天冬氨酸受体（NMDAR）的作用，该受体在较低频率的突触信号中有牵连。应用D-2-氨基-5-膦酰基戊酸（APV），一种有效的NMDAR抑制剂，在高频MF刺激期间强烈损害GC放电频率。APV对静息膜电位下1 Hz诱发的单个兴奋性突触后电位（EPSP）或电流（EPSC）无显著影响。然而，在1 Hz的去极化电位或高频MF刺激后诱发的EPSC的时间过程被APV加速。因此，我们的研究结果表明，NMDAR介导的电流放大高频MF输入延长突触输入的时程，从而导致更大的突触总和的输入。因此，NMDAR支持频率高达至少750 Hz的MF突触输入的整合。(C)2016 Wiley Periodicals，Inc.
Neuronal integration of high-frequency signals is important for rapid information processing. Cerebellar mossy fiber axons (MFs) can fire action potentials (APs) at frequencies of more than one kilohertz. However, it is unclear whether and how the postsynaptic cerebellar granule cells (GCs) are able to process these high-frequency MF inputs. Here, we measured AP firing in GCs during high-frequency MF stimulation and show that GC firing frequency increased non-linearly when MF stimulation frequency was increased from 100 to 750 Hz. To investigate the mechanisms enabling such high-frequency signaling, we analyzed the role of N-methyl-D-aspartate receptors (NMDARs), which have been implicated in synaptic signaling at lower frequencies. Application of D-2-amino-5-phosphonopentanoic acid (APV), a potent inhibitor of NMDARs, strongly impaired the GC firing frequency during high-frequency MF stimulation. APV had no significant effect on single excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) evoked at 1 Hz at resting membrane potentials. However, the time course of EPSCs evoked at 1 Hz at depolarized potentials or following high-frequency MF stimulation was accelerated by APV. Thus, our results show that NMDAR-mediated currents amplify high-frequency MF inputs by prolonging the time courses of synaptic inputs, thereby causing greater synaptic summation of inputs. Hence, NMDARs support the integration of MF synaptic input at frequencies up to at least 750 Hz. (C) 2016 Wiley Periodicals, Inc.