用神经微分方程补全生物神经元模型中的未知通道动力学。
Learning Hybrid Biophysical Neuron Models with Neural ODEs
- 将神经微分方程嵌入电导基模型,自动学习未知电流动力学。
- 在2400个通道模型上准确拟合门控动力学,单次记录即可恢复未知机制。
- 可大幅降低复杂模型计算成本,适合神经建模与计算神经科学领域。
生物神经元模型将神经活动测量与细胞机制联系起来,但许多离子通道的动力学特性未被充分描述。实际简化(如忽略通道或减少形态细节)会引入模型与生物学之间的系统性偏差。为弥合这一差距,需具备灵活发现未知动态同时保持机制可解释性的方法。本文提出一种混合建模框架,将神经常微分方程(Neural ODE)嵌入电导基生物神经元模型中,以捕捉未知电流或误设的通道动力学。通过将神经ODE参数化为电压依赖的稳态和时间常数函数,我们直接从电压记录中恢复可解释的门控动力学,无需假设函数形式。实验表明,该混合模型可准确拟合2400个离子通道模型的门控动力学,并仅凭单次电流钳记录恢复未知门控机制,在真实输入和参数误设下仍具泛化能力。此外,我们利用该方法将皮层神经元的多舱室模型简化为单舱室混合模型,通过学习轴向电流,计算成本降低达一个数量级。结果表明,该方法提供了一种即插即用的框架,可选择性替换电导基模型中未知组件,同时保留其机制结构。
原文摘要 · Abstract (English)
Biophysical neuron models link measurements of neural activity to underlying cellular mechanisms. Yet, a central challenge is that the kinetics of many ion channels are poorly characterized, and practical simplifications -- omitting channels or reducing morphological detail -- introduce systematic gaps between model and biology. Bridging these gaps requires approaches that can flexibly discover unmodeled dynamics while preserving mechanistic interpretability. Here, we introduce a hybrid modeling framework that embeds neural ordinary differential equations into conductance-based biophysical models to capture unknown currents or mis-specified channel kinetics. By parameterizing the neural ODE in terms of voltage-dependent steady-state and time-constant functions, we recover interpretable gating dynamics directly from voltage recordings without assuming a functional form. We show that the hybrid model fits the gating kinetics of 2400 ion channel models and recovers unknown gating dynamics from single current-clamp recordings, generalizing to out-of-distribution stimulus regimes under realistic inputs and parameter misspecification. We also use our method to reduce a multicompartment model of a cortical neuron into a single-compartment hybrid model with a learned axial current, yielding up to an order of magnitude lower computational cost. Together, our results establish a plug-and-play framework for selectively replacing unknown components of conductance-based models with neural ODEs while preserving their mechanistic structure.
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