Fabbri Rachele, Botte Ermes, Ahluwalia Arti, Magliaro Chiara
Research Center "E. Piaggio", University of Pisa, Pisa, Italy.
Department of Information Engineering (DII), University of Pisa, Pisa, Italy.
Front Neuroinform. 2025 Jul 1;19:1549916. doi: 10.3389/fninf.2025.1549916. eCollection 2025.
Computational models are valuable tools for understanding and studying a wide range of characteristics and mechanisms of the brain. Furthermore, they can also be exploited to explore biological neural networks from neuronal cultures. However, few of the current in silico approaches consider the energetic demand of neurons to sustain their electrophysiological functions, specifically their well-known oxygen-dependent firing.
In this work, we introduce Digitoids, a computational platform which integrates a Hodgkin-Huxley-like model to describe the time-dependent oscillations of the neuronal membrane potential with oxygen dynamics in the culture environment. In Digitoids, neurons are connected to each other according to Small-World topologies observed in cell cultures, and oxygen consumption by cells is modeled as limited by diffusion through the culture medium. The oxygen consumed is used to fuel their basal metabolism and the activity of Na-K-ATP membrane pumps, thus it modulates neuronal firing.
Our simulations show that the characteristics of neuronal firing predicted throughout the network are related to oxygen availability. In addition, the average firing rate predicted by Digitoids is statistically similar to that measured in neuronal networks , further proving the relevance of this platform.
Digitoids paves the way for a new generation of models of neuronal networks, establishing the oxygen dependence of electrophysiological dynamics as a fundamental requirement to improve their physiological relevance.
计算模型是理解和研究大脑广泛特征及机制的宝贵工具。此外,它们还可用于从神经元培养物中探索生物神经网络。然而,当前的计算机模拟方法中很少有考虑神经元维持其电生理功能所需的能量需求,特别是其众所周知的氧依赖放电。
在这项工作中,我们引入了Digitoids,这是一个计算平台,它整合了一个类似霍奇金-赫胥黎的模型,以描述神经元膜电位随时间的振荡以及培养环境中的氧动力学。在Digitoids中,神经元根据在细胞培养物中观察到的小世界拓扑结构相互连接,细胞的氧消耗被建模为受通过培养基扩散的限制。消耗的氧用于为其基础代谢和钠钾ATP膜泵的活动提供能量,从而调节神经元放电。
我们的模拟表明,整个网络预测的神经元放电特征与氧可用性有关。此外,Digitoids预测的平均放电率在统计学上与在神经网络中测量的相似,进一步证明了该平台的相关性。
Digitoids为新一代神经网络模型铺平了道路,将电生理动力学的氧依赖性确立为提高其生理相关性的基本要求。