Reynolds T, Hartell N A
The Pharmaceutical Sciences Institute, Division of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):563-77. doi: 10.1111/j.1469-7793.2000.00563.x.
Whole-cell excitatory postsynaptic currents (EPSCs) were recorded from single Purkinje cells (PCs) in rat cerebellar slices in response to alternate activation of two separate sets of parallel fibres (PF1 and PF2). Pairing the stimulation of one input (PF1) with PC depolarisation at 1 Hz for 5 min produced varied effects, including a long-term depression (LTD) of subsequent responses, a medium-term potentiation, or no change relative to baseline levels (n = 14). In all but two cases PF2 responses mirrored those in PF1, in both direction and magnitude even though this second pathway was not specifically activated during pairing. Increasing the stimulus strength to evoke larger amplitude EPSCs (> 1000 pA) dramatically increased the proportion of cells that underwent LTD in both PF1 and PF2. LTD in both pathways was postsynaptic calcium dependent. PC depolarisation alone (n = 7) or PF1 stimulation paired with PC hyperpolarisation (n = 6) failed to induce LTD at either site. Pairing PF1 stimulation with climbing fibre (CF) activation at 1 Hz for 5 min produced LTD in the majority of cells regardless of the strength of PF stimulation. LTD under these conditions was not, however, input specific, even at the lowest stimulus strengths. With EPSCs greater than 1000 pA in amplitude, depression was apparent in both pathways even when the duration of PF1 pairing with depolarisation was limited to 1 min. Full expression of LTD in PF2 required stimulation of this pathway to be resumed within a distinct temporal window of conjunctive pairing with PF1. Introducing a delay of 20 min before resumption of PF2 activation preserved the input specificity of synaptic depression. We conclude that pairing either PC depolarisation or CF activation with stimulation of a discrete set of PFs produces LTD that spreads to adjacent synapses on the same PC.
全细胞兴奋性突触后电流（EPSCs）记录于大鼠小脑切片中的单个浦肯野细胞（PCs），以响应两组不同平行纤维（PF1和PF2）的交替激活。以1Hz频率将一个输入（PF1）的刺激与PC去极化配对5分钟产生了多种效应，包括后续反应的长期抑制（LTD）、中期增强，或相对于基线水平无变化（n = 14）。除两例之外，在所有情况下，PF2反应在方向和幅度上均与PF1反应相似，尽管在配对期间第二条通路未被特异性激活。增加刺激强度以诱发更大幅度的EPSCs（> 1000 pA）显著增加了在PF1和PF2中经历LTD的细胞比例。两条通路中的LTD均为突触后钙依赖性。单独的PC去极化（n = 7）或PF1刺激与PC超极化配对（n = 6）均未能在任一部位诱导LTD。以1Hz频率将PF1刺激与攀爬纤维（CF）激活配对5分钟，在大多数细胞中产生了LTD，而与PF刺激的强度无关。然而，在这些条件下的LTD并非输入特异性的，即使在最低刺激强度下也是如此。当EPSCs幅度大于1000 pA时，即使PF1与去极化配对的持续时间限制为1分钟，两条通路中均出现明显的抑制。PF2中LTD的完全表达需要在与PF1联合配对的特定时间窗口内恢复对该通路的刺激。在恢复PF2激活之前引入20分钟的延迟保留了突触抑制的输入特异性。我们得出结论，将PC去极化或CF激活与一组离散PF的刺激配对会产生LTD，并扩散到同一PC上的相邻突触。
