Relative roles of different mechanisms of depression at the mouse endbulb of Held.
Relative roles of different mechanisms of depression at the mouse endbulb of Held.
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小鼠 Held 球端不同抑制机制的相对作用。
DOI：
10.1152/jn.01293.2007
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发表时间：
2008
影响因子：
2.5
通讯作者：
Xu-Friedman,MatthewA
中科院分区：
文献类型：
--
作者：
Yang,Hua;Xu-Friedman,MatthewA
有几种机制可以作为短期突触抑制的基础，包括囊泡耗竭、受体脱敏和突触前释放概率的变化。为了确定在生理条件下影响抑郁症的机制，我们研究了听觉神经纤维在耳蜗前腹核（“Held的endbulb”）中的浓密细胞上形成的突触，使用接近生理温度的P15-P21小鼠脑切片的电压钳记录。对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和N-甲基-d-天冬氨酸（NMDA）兴奋性突触后电流（EPSC）的抑制均表现为两个恢复阶段。环噻嗪和阿尼西坦可消除AMPA EPSC的快速抑制成分，提示其为脱敏作用的结果。低亲和力拮抗剂1-AP 5降低了NMDA EPSC的快速抑制成分，表明其来自饱和。AMPA和NMDA成分的其余抑制是相同的，因此起源于突触前。这可能是由于突触前囊泡耗尽。从抑郁症的恢复后，列车的活动被减缓的应用EGTA-AM，这表明endbulb有一个残余的钙依赖形式的恢复。我们开发了一个模型，包括消耗，脱敏，钙依赖性恢复。该模型在一系列实验条件下复制了实验结果。该模型进一步表明，在长时间的活动中，脱敏只起很小的作用，这在很大程度上是因为突触前释放被耗尽了。因此，耗尽似乎是在正常活动期间内球抑制的主要机制。此外，钙依赖的恢复在endbulb是至关重要的，以防止完全耗尽在高活动和保持信息传输的可靠性。
Several mechanisms can underlie short-term synaptic depression, including vesicle depletion, receptor desensitization, and changes in presynaptic release probability. To determine which mechanisms affect depression under physiological conditions, we studied the synapse formed by auditory nerve fibers onto bushy cells in the anteroventral cochlear nucleus (the “endbulb of Held”) using voltage-clamp recordings of brain slices from P15–P21 mice near physiological temperatures. Depression of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) andN-methyl-d-aspartate (NMDA) excitatory postsynaptic currents (EPSCs) showed two phases of recovery. The fast component of depression for the AMPA EPSC was eliminated by cyclothiazide and aniracetam, suggesting it results from desensitization. The fast component of depression for the NMDA EPSC was reduced by the low-affinity antagonistl-AP5, suggesting it results from saturation. The remaining depression in AMPA and NMDA components is identical and therefore presynaptic in origin. It is likely to result from presynaptic vesicle depletion. Recovery from depression after trains of activity was slowed by the application of EGTA-AM, suggesting that the endbulb has a residual-calcium-dependent form of recovery. We developed a model that incorporates depletion, desensitization, and calcium-dependent recovery. This model replicated experimental findings over a range of experimental conditions. The model further indicated that desensitization plays only a minor role during prolonged activity, in large part because presynaptic release is so depleted. Thus depletion appears to be the dominant mechanism of depression at the endbulb during normal activity. Furthermore, calcium-dependent recovery at the endbulb is critical to prevent complete rundown during high activity and to preserve the reliability of information transmission.
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收敛对尖峰时序影响的动态钳位分析。
DOI：
10.1152/jn.01308.2004
发表时间：
2005
期刊：
Journal of neurophysiology.
影响因子：
--
作者：
Xu-Friedman,MatthewA;Regehr,WadeG
通讯作者：
Regehr,WadeG
Held 花萼短期可塑性的生物物理模型
影响因子：
6
作者：
Matthias H Hennig;M. Postlethwaite;I. Forsythe;B. Graham
通讯作者：
B. Graham
影响因子：
56.9
作者：
BETZ, WJ;BEWICK, GS
通讯作者：
BEWICK, GS
阿尼西坦和环噻嗪选择性增强大鼠小脑切片中 AMPA 受体介导的突触兴奋
影响因子：
4.4
作者：
Andrew R. Boxall;J. Garthwaite
通讯作者：
J. Garthwaite
影响因子：
2.5
作者：
Taberner, AM;Liberman, MC
通讯作者：
Liberman, MC