Dopamine plays a critical role in modulating the long-term synaptic plasticity of the hippocampal Schaffer collateral-CA1 pyramidal neuron synapses (SC-CA1), a widely accepted cellular model of learning and memory. Limited results from hippocampal slice experiments over the last four decades have shown that the timing of the activation of dopamine D1/D5 receptors relative to a high/low-frequency stimulation (HFS/LFS) in SC-CA1 synapses regulates the modulation of HFS/LFS-induced long-term potentiation/depression (LTP/LTD) in these synapses. However, the existing literature lacks a complete picture of how various concentrations of D1/D5 agonists and the relative timing between the activation of D1/D5 receptors and LTP/LTD induction by HFS/LFS, affect the spatiotemporal modulation of SC-CA1 synaptic dynamics. In this paper, we have developed a computational model, a first of its kind, to make quantitative predictions of the temporal dose-dependent modulation of the HFS/LFS induced LTP/LTD in SC-CA1 synapses by various D1/D5 agonists. Our model combines the biochemical effects with the electrical effects at the electrophysiological level. We have estimated the model parameters from the published electrophysiological data, available from diverse hippocampal CA1 slice experiments, in a Bayesian framework. Our modeling results demonstrate the capability of our model in making quantitative predictions of the available experimental results under diverse HFS/LFS protocols. The predictions from our model show a strong nonlinear dependency of the modulated LTP/LTD by D1/D5 agonists on the relative timing between the activated D1/D5 receptors and the HFS/LFS protocol and the applied concentration of D1/D5 agonists.

多巴胺在调节海马 Schaffer 侧枝-CA1 锥体神经元突触 (SC-CA1) 的长期突触可塑性中起关键作用，SC-CA1 是一种被广泛接受的学习和记忆细胞模型。过去 40 年海马切片实验的有限结果表明，多巴胺 D1/D5 受体相对于 SC-CA1 突触中高/低频刺激 (HFS/LFS) 的激活时间调节 HFS/ LFS 诱导的这些突触中的长期增强/抑制 (LTP/LTD)。然而，现有文献缺乏关于不同浓度的 D1/D5 激动剂以及 D1/D5 受体激活与 HFS/LFS 诱导 LTP/LTD 之间的相对时间如何影响 SC-CA1 突触动力学的时空调制的完整图片。 . 在本文中，我们开发了一种计算模型，这是同类中的第一个，对各种 D1/D5 激动剂在 SC-CA1 突触中 HFS/LFS 诱导的 LTP/LTD 的时间剂量依赖性调制进行定量预测。我们的模型将生化效应与电生理水平的电效应相结合。我们在贝叶斯框架中根据已发表的电生理数据估计了模型参数，这些数据可从各种海马 CA1 切片实验中获得。我们的建模结果证明了我们的模型在各种 HFS/LFS 协议下对可用实验结果进行定量预测的能力。