Jaras Ismael, Orchard Marcos E, Maldonado Pedro E, Vergara Rodrigo C
Department of Electrical Engineering, Faculty of Mathematical and Physical Sciences, University of Chile, Santiago, Chile.
Neurosystems Laboratory, Department of Neuroscience, Faculty of Medicine, University of Chile, Santiago, Chile.
PLoS Comput Biol. 2025 Jun 13;21(6):e1013148. doi: 10.1371/journal.pcbi.1013148. eCollection 2025 Jun.
Understanding the intricate interplay between neural dynamics and metabolic constraints is crucial for unraveling the mysteries of the brain. Despite the significance of this relationship, specific details concerning the impact of metabolism on neuronal dynamics and neural network architecture remain elusive, creating a notable gap in the existing literature. This study employs an energy-dependent neuron and plasticity model to analyze the role of local metabolic constraints in shaping both the dynamics and structure of Spiking Neural Networks (SNN). Specifically, an energy-dependent version of the leaky integrate-and-fire model is utilized, along with a three-factor learning rule that incorporates postsynaptic available energy as the third factor. These models allow for fine-tuning sensitivity in the presence of energy imbalances. Analytical expressions predicting the network's activity and structure are derived, and a fixed point analysis reveals the emergence of attractor states characterized by neuronal and synaptic sensitivity to energy imbalances. Analytical findings are validated through numerical simulations using an excitatory-inhibitory network. Furthermore, these simulations enable the study of SNN activity and structure under conditions simulating metabolic impairment. In conclusion, by employing energy-dependent models with adjustable sensitivity to energy imbalances, our study advances the understanding of how metabolic constraints shape SNN dynamics and structure. Moreover, in light of compelling evidence linking neuronal metabolic impairment to neurodegenerative diseases, the incorporation of local metabolic constraints into the investigation of neuronal network structure and activity opens an intriguing avenue for inspiring the development of therapeutic interventions.
理解神经动力学与代谢限制之间复杂的相互作用对于揭开大脑奥秘至关重要。尽管这种关系意义重大,但关于代谢对神经元动力学和神经网络结构影响的具体细节仍然难以捉摸,这在现有文献中造成了明显的空白。本研究采用了一个能量依赖型神经元和可塑性模型,以分析局部代谢限制在塑造脉冲神经网络(SNN)的动力学和结构方面所起的作用。具体而言,使用了泄漏积分发放模型的能量依赖版本,以及一种三因素学习规则,该规则将突触后可用能量作为第三个因素纳入其中。这些模型能够在存在能量失衡的情况下微调敏感性。推导了预测网络活动和结构的解析表达式,定点分析揭示了以神经元和突触对能量失衡的敏感性为特征的吸引子状态的出现。通过使用兴奋性 - 抑制性网络的数值模拟对分析结果进行了验证。此外,这些模拟能够研究在模拟代谢损伤条件下SNN的活动和结构。总之,通过采用对能量失衡具有可调敏感性的能量依赖型模型,我们的研究推进了对代谢限制如何塑造SNN动力学和结构的理解。此外,鉴于将神经元代谢损伤与神经退行性疾病联系起来的有力证据,将局部代谢限制纳入对神经网络结构和活动的研究为激发治疗干预措施的发展开辟了一条有趣的途径。