Separation of Presynaptic and Postsynaptic Contributions to Depression by Covariance Analysis of Successive EPSCs at the Calyx of Held Synapse
Separation of Presynaptic and Postsynaptic Contributions to Depression by Covariance Analysis of Successive EPSCs at the Calyx of Held Synapse
复制标题
DOI：
10.1523/jneurosci.22-03-00728.2002
复制
发表时间：
2002-02
期刊：
影响因子：
--
通讯作者：
V. Scheuss;R. Schneggenburger;E. Neher
中科院分区：
文献类型：
--
作者：
V. Scheuss;R. Schneggenburger;E. Neher
突触短期可塑性被认为是由多种细胞机制引起的，其中可能包括突触前和突触后的贡献。我们最近开发了一种非平稳EPSC波动分析（Scheuss和Neher，2001），以估计突触参数和他们的短期突触可塑性的瞬态变化。扩展经典的方差-均值方法，一个短的刺激列车重复应用，并分析所得到的EPSC的均值，方差和协方差。这提供了序列中每个EPSC的量子大小和量子含量的估计，以及释放位点数量的估计。后者是不太敏感的异质性的释放概率比方差均值的方法。在这里，我们应用这种分析的萼举行突触在脑干切片的年轻大鼠（出生后第8-10天）。我们发现显着的负协方差的幅度连续EPSC在一列火车。分析表明，在100 Hz的列车在细胞外Ca 2+浓度升高的EPSC振幅的10倍的抑郁症导致突触后AMPA受体脱敏和饱和引起的量子大小减少2.5倍，量子含量减少4倍，这是部分缓解应用环噻嗪。通过协方差分析估计的释放位点的数量为10000，显著大于方差均值抛物线的估计值。
Synaptic short-term plasticity is considered to result from multiple cellular mechanisms, which may include presynaptic and postsynaptic contributions. We have recently developed a nonstationary EPSC fluctuation analysis (Scheuss and Neher, 2001) to estimate synaptic parameters and their transient changes during short-term synaptic plasticity. Extending the classical variance–mean approach, a short train of stimuli is applied repetitively, and the resulting EPSCs are analyzed for means, variances, and covariances. This provides estimates of the quantal size and quantal content for each EPSC in the train, and furthermore, an estimate of the number of release sites. The latter is less sensitive to heterogeneity in the release probability than that of the variance–mean approach. Here, we applied this analysis to the calyx of Held synapse in brainstem slices of young rats (postnatal day 8–10). We found significant negative covariance in the amplitude of successive EPSCs in a train. The analysis showed that the 10-fold depression in the EPSC amplitude during 100 Hz trains at elevated extracellular Ca2+ concentration resulted from a 2.5-fold reduction in quantal size caused by postsynaptic AMPA receptor desensitization and saturation, and a fourfold reduction in quantal content, which was partially relieved by application of cyclothiazide. The number of release sites estimated by covariance analysis was ≈2000 and significantly larger than estimates from variance–mean parabolas.