TY - JOUR
T1 - Representing Stimulus Information in an Energy Metabolism Pathway
AU - Coggan, Jay S
AU - Keller, Daniel
AU - Markram, Henry
AU - Schürmann, Felix
AU - Magistretti, Pierre J.
N1 - KAUST Repository Item: Exported on 2022-04-26
Acknowledged 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)
PY - 2022/3/14
Y1 - 2022/3/14
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/676460
UR - https://linkinghub.elsevier.com/retrieve/pii/S0022519322000881
UR - http://www.scopus.com/inward/record.url?scp=85126269417&partnerID=8YFLogxK
U2 - 10.1016/j.jtbi.2022.111090
DO - 10.1016/j.jtbi.2022.111090
M3 - Article
C2 - 35271865
SN - 0022-5193
VL - 540
SP - 111090
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
ER -