Abstract
We explored a computational model of astrocytic energy metabolism and demonstrated the theoretical plausibility that this type of pathway might be capable of coding information about stimuli in addition to its known functions in cellular energy and carbon budgets. Simulation results indicate that glycogenolytic glycolysis triggered by activation of adrenergic receptors can capture the intensity and duration features of a neuromodulator waveform and can respond in a dose-dependent manner, including non-linear state changes that are analogous to action potentials. We show how this metabolic pathway can translate information about external stimuli to production profiles of energy-carrying molecules such as lactate with a precision beyond simple signal transduction or non-linear amplification. The results suggest the operation of a metabolic state-machine from the spatially discontiguous yet interdependent metabolite elements. Such metabolic pathways might be well-positioned to code an additional level of salient information about a cell's environmental demands to impact its function. Our hypothesis has implications for the computational power and energy efficiency of the brain.
Original language | English (US) |
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Pages (from-to) | 111090 |
Journal | Journal of Theoretical Biology |
Volume | 540 |
DOIs | |
State | Published - Mar 14 2022 |
Bibliographical note
KAUST Repository Item: Exported on 2022-04-26Acknowledged KAUST grant number(s): OSR-2017-CRG6-3438
Acknowledgements: The authors thank the Molecular Systems group at the Blue Brain Project for helpful discussions and Alessandro Foni for the Graphical Abstract illustration. Supported by a CRG grant from King Abdullah University of Science and Technology "KAUST-EPFL Alliance for Integrative Modeling of Brain Energy Metabolism" [OSR-2017-CRG6-3438] (PJM); the Blue Brain Project, a research center of the École Polytechnique Fédérale de Lausanne, from the Swiss government's ETH Board of the Swiss Federal Institutes of Technology (HM); and NCCR Synapsy (PJM)
ASJC Scopus subject areas
- General Agricultural and Biological Sciences
- General Biochemistry, Genetics and Molecular Biology
- Modeling and Simulation
- Applied Mathematics
- Statistics and Probability
- General Immunology and Microbiology
- General Medicine