ArticlePLoS computational biology2015
Multi-timescale modeling of activity-dependent metabolic coupling in the neuron-glia-vasculature ensemble.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Neural Stimulation and Molecular Mechanisms of Plasticity and Regeneration: A Review.Frontiers in cellular neuroscience · 2020Pooled it
- Computational Modeling of Neurotransmitter Cycling Predicts Human Brain Glutamate and GABA Dynamics in Response to Acute Administration of Exogenous Ketones.Neurochemical research · 2026Article
- A scoping review of computational models on human glucose cerebral metabolism.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Presynaptic ATP Decreases During Physiological-Like Activity in Neurons Tuned for High-Frequency Transmission.Journal of neurochemistry · 2025Article
- Elucidating reaction dynamics in a model of human brain energy metabolism.PLoS computational biology · 2025Article
- A primary mechanism for efficacy of the ketogenic diet may be energy repletion at the tripartite synapse.Journal of neural engineering · 2025Article
- Unveiling the role of local metabolic constraints on the structure and activity of spiking neural networks.PLoS computational biology · 2025Article
- A multiscale electro-metabolic model of a rat neocortical circuit reveals the impact of ageing on central cortical layers.PLoS computational biology · 2025Article
- Seizure and redox rescue in a model of glucose transport deficiency.PLoS computational biology · 2025Article
- Dialogue mechanisms between astrocytic and neuronal networks: A whole-brain modelling approach.PLoS computational biology · 2025Article
- Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.Cells · 2024Review
- Astrocytes: new evidence, new models, new roles.Biophysical reviews · 2023Review
- Mechanistic multiscale modelling of energy metabolism in human astrocytes reveals the impact of morphology changes in Alzheimer's Disease.PLoS computational biology · 2023Article
- Technical feasibility of multimodal imaging in neonatal hypoxic-ischemic encephalopathy from an ovine model to a human case series.Frontiers in pediatrics · 2023Article
- Lactate supply overtakes glucose when neural computational and cognitive loads scale up.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Human-in-the-Loop Optimization of Transcranial Electrical Stimulation at the Point of Care: A Computational Perspective.Brain sciences · 2022Article
- How expensive is the astrocyte?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Perspective: Disentangling the effects of tES on neurovascular unit.Frontiers in neurology · 2022Article
- Ion dynamics at the energy-deprived tripartite synapse.PLoS computational biology · 2021Article
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain's metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging.
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