Bernstein Center Freiburg, University of Freiburg Freiburg, Germany.
Front Comput Neurosci. 2011 Sep 29;5:38. doi: 10.3389/fncom.2011.00038. eCollection 2011.
The NMDAR-dependent synaptic plasticity is thought to mediate several forms of learning, and can be induced by spike trains containing a small number of spikes occurring with varying rates and timing, as well as with oscillations. We computed the influence of these variables on the plasticity induced at a single NMDAR containing synapse using a reduced model that was analytically tractable, and these findings were confirmed using detailed, multi-compartment model. In addition to explaining diverse experimental results about the rate and timing dependence of synaptic plasticity, the model made several novel and testable predictions. We found that there was a preferred frequency for inducing long-term potentiation (LTP) such that higher frequency stimuli induced lesser LTP, decreasing as 1/f when the number of spikes in the stimulus was kept fixed. Among other things, the preferred frequency for inducing LTP varied as a function of the distance of the synapse from the soma. In fact, same stimulation frequencies could induce LTP or long-term depression depending on the dendritic location of the synapse. Next, we found that rhythmic stimuli induced greater plasticity then irregular stimuli. Furthermore, brief bursts of spikes significantly expanded the timing dependence of plasticity. Finally, we found that in the ∼5-15-Hz frequency range both rate- and timing-dependent plasticity mechanisms work synergistically to render the synaptic plasticity most sensitive to spike timing. These findings provide computational evidence that oscillations can have a profound influence on the plasticity of an NMDAR-dependent synapse, and show a novel role for the dendritic morphology in this process.
NMDAR 依赖性突触可塑性被认为介导了几种形式的学习，并且可以通过具有不同速率和时间以及振荡的少量尖峰的尖峰序列来诱导。我们使用可分析处理的简化模型计算了这些变量对单个包含 NMDAR 的突触诱导的可塑性的影响，并且使用详细的多室模型确认了这些发现。除了解释关于突触可塑性的速率和时间依赖性的各种实验结果外，该模型还做出了一些新颖且可测试的预测。我们发现，存在诱导长时程增强（LTP）的最佳频率，使得较高频率的刺激诱导较少的 LTP，当刺激中的尖峰数量保持固定时，随着 1/f 而减少。除其他外，诱导 LTP 的最佳频率随突触与胞体的距离而变化。实际上，相同的刺激频率可以根据突触的树突位置诱导 LTP 或长时程抑制。接下来，我们发现，节律性刺激比不规则刺激诱导更大的可塑性。此外，短暂的尖峰爆发显着扩展了可塑性的时间依赖性。最后，我们发现，在约 5-15 Hz 的频率范围内，基于速率和基于时间的可塑性机制协同作用，使突触可塑性对尖峰时间最为敏感。这些发现为计算提供了证据，表明振荡可以对 NMDAR 依赖性突触的可塑性产生深远的影响，并显示出树突形态在该过程中的新作用。
