Inferring the dynamics of ionic currents from recursive piecewise data assimilation of approximate neuron models

Stephen A. Wells, Joseph D. Taylor, Paul G. Morris, Alain Nogaret
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Abstract

We construct neuron models from data by transferring information from an observed time series to the state variables and parameters of Hodgkin-Huxley models. When the learning period completes, the model will predict additional observations and its parameters uniquely characterise the complement of ion channels. However, the assimilation of biological data, as opposed to model data, is complicated by the lack of knowledge of the true neuron equations. Reliance on guessed conductance models is plagued with multi-valued parameter solutions. Here, we report on the distributions of parameters and currents predicted with intentionally erroneous models, over-specified models, and an approximate model fitting hippocampal neuron data. We introduce a recursive piecewise data assimilation (RPDA) algorithm that converges with near-perfect reliability when the model is known. When the model is unknown, we show model error introduces correlations between certain parameters. The ionic currents reconstructed from these parameters are excellent predictors of true currents and carry a higher degree of confidence, >95.5%, than underlying parameters, >53%. Unexpressed ionic currents are correctly filtered out even in the presence of mild model error. When the model is unknown, the covariance eigenvalues of parameter estimates are found to be a good gauge of model error. Our results suggest that biological information may be retrieved from data by focussing on current estimates rather than parameters.
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从近似神经元模型的递归分片数据同化中推断离子电流的动态变化
我们将观测到的时间序列信息转移到霍奇金-赫胥黎模型的状态变量和参数中,从而根据数据构建神经元模型。当学习期结束时,模型将预测更多的观测数据,其参数将唯一地描述离子通道的互补性。然而,与模型数据相比,生物数据的同化因缺乏对真实神经元方程的了解而变得复杂。在这里,我们报告了用故意错误的模型、过度指定的模型和拟合海马神经元数据的近似模型预测的参数和电流分布。我们介绍了一种递归片断数据同化(RPDA)算法,当模型已知时,该算法以近乎完美的可靠性收敛。当模型未知时,我们发现模型错误会引入某些参数之间的相关性。根据这些参数重建的离子电流可以很好地预测真实电流,其置信度大于 95.5%,高于基础参数的置信度(大于 53%)。即使存在轻微的模型误差,也能正确过滤出未表达的离子电流。我们的研究结果表明,通过关注电流估计值而不是参数,可以从数据中获取生物学信息。
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