Lumeij Lucas B, van Huijstee Aile N, Cappaert Natalie L M, Kessels Helmut W
Cellular and Computational Neuroscience, Swammerdam Institute for Life Sciences, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands.
Front Cell Neurosci. 2023 Jul 17;17:1232541. doi: 10.3389/fncel.2023.1232541. eCollection 2023.
Our knowledge on synaptic transmission in the central nervous system has often been obtained by evoking synaptic responses to populations of synapses. Analysis of the variance in synaptic responses can be applied as a method to predict whether a change in synaptic responses is a consequence of altered presynaptic neurotransmitter release or postsynaptic receptors. However, variance analysis is based on binomial statistics, which assumes that synapses are uniform. In reality, synapses are far from uniform, which questions the reliability of variance analysis when applying this method to populations of synapses. To address this, we used an model for evoked synaptic responses and compared variance analysis outcomes between populations of uniform versus non-uniform synapses. This simulation revealed that variance analysis produces similar results irrespectively of the grade of uniformity of synapses. We put this variance analysis to the test with an electrophysiology experiment using a model system for which the loci of plasticity are well established: the effect of amyloid-β on synapses. Variance analysis correctly predicted that postsynaptically produced amyloid-β triggered predominantly a loss of synapses and a minor reduction of postsynaptic currents in remaining synapses with little effect on presynaptic release probability. We propose that variance analysis can be reliably used to predict the locus of synaptic changes for populations of non-uniform synapses.
我们对中枢神经系统突触传递的认识常常是通过激发对突触群体的突触反应而获得的。对突触反应方差的分析可作为一种方法，用于预测突触反应的变化是突触前神经递质释放改变还是突触后受体改变的结果。然而，方差分析基于二项式统计，该统计假设突触是均匀的。实际上，突触远非均匀，这使得将该方法应用于突触群体时方差分析的可靠性受到质疑。为了解决这个问题，我们使用了一个诱发突触反应的模型，并比较了均匀突触群体与非均匀突触群体之间的方差分析结果。该模拟表明，无论突触的均匀程度如何，方差分析都会产生相似的结果。我们通过一个电生理实验对这种方差分析进行了测试，该实验使用了一个可塑性位点已明确的模型系统：淀粉样β蛋白对突触的影响。方差分析正确地预测出，突触后产生的淀粉样β蛋白主要引发突触丢失，以及剩余突触中突触后电流的轻微减少，而对突触前释放概率影响很小。我们提出，方差分析可可靠地用于预测非均匀突触群体的突触变化位点。
