Context-dependent effects of NMDA receptors on precise timing information at the endbulb of Held in the cochlear nucleus.
Context-dependent effects of NMDA receptors on precise timing information at the endbulb of Held in the cochlear nucleus.
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NMDA 受体对耳蜗核中 Held 球的精确计时信息的上下文依赖性影响。
DOI：
10.1152/jn.00111.2009
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发表时间：
2009
影响因子：
2.5
通讯作者：
Xu-Friedman,MatthewA
中科院分区：
文献类型：
--
作者：
Pliss,Lioudmila;Yang,Hua;Xu-Friedman,MatthewA
许多突触同时包含AMPA受体（AMPAR）和n -甲基-d-天冬氨酸受体（NMDAR），但它们在突触计算中的不同作用尚不清楚。我们在耳蜗核的丛状细胞上形成的听神经纤维突触（称为Held终球）上解决了这个问题。末梢球精炼并将精确的时间信息传递给负责声音定位的细胞核。终球具有许多有助于精确计时的特化，包括ampar介导的具有快速动力学的兴奋性突触后电流（EPSCs）。小鼠脑切片的电压钳实验显示，在成熟的终末球中，缓慢的NMDAR EPSC得以维持，其峰值电导约为ampar介导的EPSC的10%。在重复的突触活动中，AMPAR EPSCs抑制，NMDAR EPSCs累积，从而增加了NMDAR的相对重要性。这可能会影响丛状细胞的时间精度，因为NMDARs的缓慢动力学。我们通过阻断NMDARs和定量电流钳中激活单端球时的丛状细胞尖峰时间来测试这一点。这些实验表明，NMDARs有助于增加触发概率，缩短延迟，减少抖动。动态钳形实验证实了这一效应，并表明其具有剂量依赖性。浓密的细胞可以接受来自多个端球的输入。当我们在动态箝位中施加多个突触输入时，NMDARs对尖峰时间的影响较小。NMDAR电导远高于成熟水平可能会破坏峰值，这可能解释了其在发育过程中的下调。因此，成熟的NMDAR表达可以根据刺激条件在终球支持精确的时间信息传递。
Many synapses contain both AMPA receptors (AMPAR) andN-methyl-d-aspartate receptors (NMDAR), but their different roles in synaptic computation are not clear. We address this issue at the auditory nerve fiber synapse (called the endbulb of Held), which is formed on bushy cells of the cochlear nucleus. The endbulb refines and relays precise temporal information to nuclei responsible for sound localization. The endbulb has a number of specializations that aid precise timing, including AMPAR-mediated excitatory postsynaptic currents (EPSCs) with fast kinetics. Voltage-clamp experiments in mouse brain slices revealed that slow NMDAR EPSCs are maintained at mature endbulbs, contributing a peak conductance of around 10% of the AMPAR-mediated EPSC. During repetitive synaptic activity, AMPAR EPSCs depressed and NMDAR EPSCs summated, thereby increasing the relative importance of NMDARs. This could impact temporal precision of bushy cells because of the slow kinetics of NMDARs. We tested this by blocking NMDARs and quantifying bushy cell spike timing in current clamp when single endbulbs were activated. These experiments showed that NMDARs contribute to an increased probability of firing, shorter latency, and reduced jitter. Dynamic-clamp experiments confirmed this effect and showed it was dose-dependent. Bushy cells can receive inputs from multiple endbulbs. When we applied multiple synaptic inputs in dynamic clamp, NMDARs had less impact on spike timing. NMDAR conductances much higher than mature levels could disrupt spiking, which may explain its downregulation during development. Thus mature NMDAR expression can support the conveying of precise temporal information at the endbulb, depending on the stimulus conditions.
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影响因子：
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