Pavlidis P, Madison D V
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, 94305-5345, USA.
J Neurophysiol. 1999 Jun;81(6):2787-97. doi: 10.1152/jn.1999.81.6.2787.
We performed simultaneous whole cell recordings from pairs of monosynaptically coupled hippocampal CA3 pyramidal neurons in organotypic slices. Stimulation of an action potential in a presynaptic cell resulted in an AMPA-receptor-mediated excitatory postsynaptic current (EPSC) in the postsynaptic cell that averaged approximately 34 pA. The average size of EPSCs varied in amplitude over a 20-fold range across different pairs. Both paired-pulse facilitation and depression were observed in the synaptic current in response to two presynaptic action potentials delivered 50 ms apart, but the average usually was dominated by depression. In addition, the amplitude of the second EPSC depended on the amplitude of the first EPSC, indicating competition between successive events for a common resource that is not restored within the 50-ms interpulse interval. Variation in the synaptic strength among pairs could arise from a variety of sources. Our data from anatomic reconstruction, 1/CV2 analysis, paired-pulse analysis, and manipulations of calcium/magnesium ratio suggest that differences in quantal size and release probability do not appear to vary sufficiently to fully account for the observed differences in amplitude. Thus it seems most likely that the variability in EPSC amplitude between pairs arises primarily from differences in the number of functional synapses. Injections of the calcium chelator bis-(o-aminophenoxy)-N, N,N',N'-tetraacetic acid into the presynaptic neuron resulted in a rapid and nearly complete block of transmission, whereas injection of the slower-acting chelator EGTA resulted in a variable and partial block. In addition to demonstrating the feasibility of manipulating the intracellular presynaptic environment by injection into the presynaptic soma, these data, and the EGTA results in particular may suggest variability in the linkage between calcium entry sites an release sites in these synapses.
我们在器官型脑片中对成对的单突触连接的海马CA3锥体神经元进行了同步全细胞记录。刺激突触前细胞产生动作电位会在突触后细胞中引发AMPA受体介导的兴奋性突触后电流（EPSC），其平均值约为34 pA。不同对的EPSC平均大小在幅度上有20倍的变化范围。在响应间隔50毫秒施加的两个突触前动作电位时，突触电流中观察到了双脉冲易化和抑制现象，但平均值通常以抑制为主。此外，第二个EPSC的幅度取决于第一个EPSC的幅度，这表明连续事件之间对一种在50毫秒脉冲间隔内无法恢复的共同资源存在竞争。成对之间突触强度的变化可能源于多种因素。我们从解剖重建、1/CV2分析、双脉冲分析以及钙/镁比例操作中获得的数据表明，量子大小和释放概率的差异似乎没有足够的变化来完全解释观察到的幅度差异。因此，最有可能的是，成对之间EPSC幅度的变异性主要源于功能性突触数量的差异。向突触前神经元注射钙螯合剂双（邻氨基苯氧基）-N，N，N'，N'-四乙酸会导致传递迅速且几乎完全阻断，而注射作用较慢的螯合剂乙二醇双四乙酸（EGTA）会导致可变的部分阻断。除了证明通过向突触前胞体注射来操纵细胞内突触前环境的可行性外，这些数据，特别是EGTA的结果可能表明这些突触中钙进入位点和释放位点之间的连接存在变异性。
