Department of Physics, University of Bath, Bath, United Kingdom.
PLoS Comput Biol. 2020 Jul 16;16(7):e1008053. doi: 10.1371/journal.pcbi.1008053. eCollection 2020 Jul.
The estimation of parameters controlling the electrical properties of biological neurons is essential to determine their complement of ion channels and to understand the function of biological circuits. By synchronizing conductance models to time series observations of the membrane voltage, one may construct models capable of predicting neuronal dynamics. However, identifying the actual set of parameters of biological ion channels remains a formidable theoretical challenge. Here, we present a regularization method that improves convergence towards this optimal solution when data are noisy and the model is unknown. Our method relies on the existence of an offset in parameter space arising from the interplay between model nonlinearity and experimental error. By tuning this offset, we induce saddle-node bifurcations from sub-optimal to optimal solutions. This regularization method increases the probability of finding the optimal set of parameters from 67% to 94.3%. We also reduce parameter correlations by implementing adaptive sampling and stimulation protocols compatible with parameter identifiability requirements. Our results show that the optimal model parameters may be inferred from imperfect observations provided the conditions of observability and identifiability are fulfilled.
估计控制生物神经元电特性的参数对于确定其离子通道的组成以及理解生物电路的功能至关重要。通过将电导模型与膜电压的时间序列观测值进行同步,可以构建能够预测神经元动力学的模型。然而,确定生物离子通道的实际参数集仍然是一个具有挑战性的理论难题。在这里,我们提出了一种正则化方法,当数据存在噪声且模型未知时,该方法可以改善向最优解收敛的速度。我们的方法依赖于参数空间中由于模型非线性和实验误差相互作用而产生的偏移的存在。通过调整这个偏移,我们可以诱导从次优到最优解的鞍结分岔。这种正则化方法将找到最优参数集的概率从 67%提高到 94.3%。我们还通过实施与参数可识别性要求兼容的自适应采样和刺激协议来降低参数相关性。我们的结果表明,只要满足可观测性和可识别性条件,就可以从不完善的观测中推断出最优模型参数。