Brody D L, Yue D T
The Johns Hopkins University School of Medicine, Departments of Biomedical Engineering and Neuroscience, Program in Molecular and Cellular Systems Physiology, Baltimore, Maryland 21205, USA.
J Neurosci. 2000 Apr 1;20(7):2480-94. doi: 10.1523/JNEUROSCI.20-07-02480.2000.
Short-term synaptic plasticity may dramatically influence neuronal information transfer, yet the underlying mechanisms remain incompletely understood. In autapses (self-synapses) formed by cultured hippocampal neurons, short-term synaptic depression (STD) had several unusual features. (1) Reduction of neurotransmitter release probability with Cd(2+), a blocker of voltage-gated calcium channels, did not change depression. (2) Lowering Ca(2+) and/or raising Mg(2+) had little effect on STD in cells with strong baseline depression, but in cells with more modest baseline depression, it reduced the depression. (3) Random variations in the size of initial EPSCs did not influence successive EPSC sizes. These findings were inconsistent with release-dependent mechanisms, such as vesicle depletion, post-synaptic receptor desensitization, and autoreceptor inhibition. Instead, other results suggested that changes in action potentials (APs) contributed to depression. The somatic APs declined in amplitude with repetitive stimulation, and modest reduction of AP amplitudes with tetrodotoxin inhibited EPSCs. Notably, tetrodotoxin also increased depression. Similar changes in axonal APs could produce STD in at least two ways. First, decreasing presynaptic spike amplitudes could reduce calcium entry and release probability. Alternatively, APs could fail to propagate through some axonal branches, reducing the number of active synapses. To explore these possibilities, we derived the expected variance of EPSCs for the two scenarios. Experimentally, the variance increased and then decreased on average with successive responses during trains of APs, confirming a unique prediction from the conduction failure scenario. Thus, STD had surprising properties, incompatible with commonly postulated mechanisms but consistent with AP conduction failure at axonal branches.
短期突触可塑性可能会显著影响神经元信息传递，但其潜在机制仍未完全明确。在培养的海马神经元形成的自突触（自身突触）中，短期突触抑制（STD）具有几个不寻常的特征。（1）用电压门控钙通道阻滞剂Cd(2+)降低神经递质释放概率，并不会改变抑制作用。（2）降低细胞外钙离子浓度Ca(2+)和/或提高细胞外镁离子浓度Mg(2+)，对具有强烈基线抑制的细胞中的STD影响很小，但在基线抑制较适度的细胞中，会降低抑制作用。（3）初始兴奋性突触后电流（EPSC）大小的随机变化不会影响后续EPSC的大小。这些发现与依赖释放的机制不一致，如囊泡耗竭、突触后受体脱敏和自身受体抑制。相反，其他结果表明动作电位（AP）的变化导致了抑制。随着重复刺激，体细胞动作电位的幅度下降，用河豚毒素适度降低动作电位幅度会抑制EPSC。值得注意的是，河豚毒素也会增加抑制作用。轴突动作电位的类似变化至少可以通过两种方式产生STD。首先，降低突触前尖峰幅度可以减少钙离子内流和释放概率。或者，动作电位可能无法通过某些轴突分支传播，从而减少活跃突触的数量。为了探究这些可能性，我们推导了两种情况下EPSC的预期方差。在实验中，随着动作电位序列中连续反应的进行，方差平均先增加后减少，证实了传导失败情况下的一个独特预测。因此，STD具有令人惊讶的特性，与通常假设的机制不相符，但与轴突分支处的动作电位传导失败一致。
