University of Tübingen, Tübingen, Germany.
Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
PLoS Comput Biol. 2020 Dec 21;16(12):e1008503. doi: 10.1371/journal.pcbi.1008503. eCollection 2020 Dec.
In this work, we introduce new phenomenological neuronal models (eLIF and mAdExp) that account for energy supply and demand in the cell as well as the inactivation of spike generation how these interact with subthreshold and spiking dynamics. Including these constraints, the new models reproduce a broad range of biologically-relevant behaviors that are identified to be crucial in many neurological disorders, but were not captured by commonly used phenomenological models. Because of their low dimensionality eLIF and mAdExp open the possibility of future large-scale simulations for more realistic studies of brain circuits involved in neuronal disorders. The new models enable both more accurate modeling and the possibility to study energy-associated disorders over the whole time-course of disease progression instead of only comparing the initially healthy status with the final diseased state. These models, therefore, provide new theoretical and computational methods to assess the opportunities of early diagnostics and the potential of energy-centered approaches to improve therapies.
在这项工作中，我们引入了新的现象神经元模型（eLIF 和 mAdExp），这些模型考虑了细胞内的能量供应和需求，以及尖峰生成的失活，以及这些因素如何与亚阈值和尖峰动力学相互作用。这些约束条件使新模型再现了广泛的具有生物学相关性的行为，这些行为被认为在许多神经疾病中至关重要，但常用的现象模型并未捕捉到这些行为。由于其低维性，eLIF 和 mAdExp 为未来的大规模模拟提供了可能性，以便更真实地研究与神经元疾病相关的脑回路。这些新模型不仅可以更准确地建模，还可以研究与能量相关的疾病在整个疾病进展过程中的整个时间过程，而不仅仅是比较最初的健康状态与最终的患病状态。因此，这些模型为评估早期诊断的机会和以能量为中心的方法改善治疗的潜力提供了新的理论和计算方法。
