Garcia-Perez Elizabeth, Wesseling John F
Departamento de Neurociencias, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pio XII, 55, 31008 Pamplona, Spain.
J Neurophysiol. 2008 Apr;99(4):1770-86. doi: 10.1152/jn.01348.2007. Epub 2008 Jan 16.
Short-term plasticity occurs at most central chemical synapses and includes both positive and negative components, but the principles governing interaction between components are largely unknown. The residual Ca(2+) that persists in presynaptic terminals for several seconds after repetitive use is known to enhance neurotransmitter release under artificial, low probability of release conditions where depression is absent; this is termed augmentation. However, the full impact of augmentation under standard conditions at synapses where depression dominates is not known because of possibly complicated convolution with a variety of potential depression mechanisms. This report shows that residual Ca(2+) continues to have a large enhancing impact on release at excitatory hippocampal synapses recovering from depression, including when only recently recruited vesicles are available for release. No evidence was found for gradual vesicle priming or for fast refilling of a highly releasable subdivision of the readily releasable pool (RRP). And decay of enhancement matched the clearance of residual Ca(2+), thus matching the behavior of augmentation when studied in isolation. Because of incomplete RRP replenishment, synaptic strength was not typically increased above baseline when residual Ca(2+) levels were highest. Instead residual Ca(2+) caused single pulse release probability to rebound quickly from depression and then depress quickly during subsequent bursts of activity. Together, these observations can help resolve discrepancies in recent timing estimates of recovery from depression. Additionally, in contrast to results obtained under reduced release conditions, augmentation could be driven to a maximal level, occluding paired-pulse facilitation and other mechanisms that increase release efficiency.
短期可塑性发生在大多数中枢化学突触，包括正性和负性成分，但关于这些成分之间相互作用的原理在很大程度上尚不清楚。已知在重复使用后，在突触前终末持续存在数秒的残余Ca(2+)在人工设定的、不存在抑制的低释放概率条件下可增强神经递质释放；这被称为增强效应。然而，在抑制占主导的标准条件下，由于可能与多种潜在的抑制机制发生复杂的卷积，增强效应的全面影响尚不清楚。本报告表明，残余Ca(2+)在从抑制中恢复的兴奋性海马突触处，对释放仍有很大的增强作用，包括当只有最近募集的囊泡可用于释放时。未发现囊泡逐步启动或快速释放池（RRP）中高释放性亚群快速再填充的证据。增强效应的衰减与残余Ca(2+)的清除相匹配，因此与单独研究时增强效应的行为相匹配。由于RRP补充不完全，当残余Ca(2+)水平最高时，突触强度通常不会增加到基线以上。相反，残余Ca(2+)导致单脉冲释放概率从抑制中迅速反弹，然后在随后的活动爆发期间迅速降低。总之，这些观察结果有助于解决近期关于从抑制中恢复的时间估计中的差异。此外，与在低释放条件下获得的结果相反，增强效应可被驱动到最大水平，从而阻断双脉冲易化和其他增加释放效率的机制。
