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  4. A multiscale electro-metabolic model of a rat neocortical circuit reveals the impact of ageing on central cortical layers
 
research article

A multiscale electro-metabolic model of a rat neocortical circuit reveals the impact of ageing on central cortical layers

Farina, Sofia
•
Cattabiani, Alessandro  
•
Mandge, Darshan  
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May 20, 2025
PLoS Computational Biology

The high energetic demands of the brain arise primarily from neuronal activity. Neurons consume substantial energy to transmit information as electrical signals and maintain their resting membrane potential. These energetic requirements are met by the neuro-glial-vascular (NGV) ensemble, which generates energy in a coupled metabolic process. In ageing, metabolic function becomes impaired, producing less energy and, consequently, the system is unable to sustain the neuronal energetic needs. We propose a multiscale model of electro-metabolic coupling in a reconstructed rat neocortex. This combines an electro-morphologically reconstructed electrophysiological model with a detailed NGV metabolic model. Our results demonstrate that the large-scale model effectively captures electro-metabolic processes at the circuit level, highlighting the importance of heterogeneity within the circuit, where energetic demands vary according to neuronal characteristics. Finally, in metabolic ageing, our model indicates that the middle cortical layers are particularly vulnerable to energy impairment.

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Type
research article
DOI
10.1371/journal.pcbi.1013070
Author(s)
Farina, Sofia
Cattabiani, Alessandro  
Mandge, Darshan  
Shichkova, Polina  
Isbister, James Bryden  
Jacquemier, Jean  
King, James Gonzalo  
Markram, Henry  

EPFL

Keller, Daniel  
Editors
Rubin, Jonathan
Date Issued

2025-05-20

Publisher

Public Library of Science (PLoS)

Published in
PLoS Computational Biology
Volume

21

Issue

5

Article Number

e1013070

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LNMC  
BBP-CORE  
FunderFunding(s)Grant NumberGrant URL

Board of the Swiss Federal Institutes of Technology

Blue Brain Project

RelationRelated workURL/DOI

IsSupplementedBy

BlueBrain / Molsys-MetabolicModel [code]

https://github.com/BlueBrain/Molsys-MetabolicModel/tree/main/Multiscale_electrometabolic_ratneocortex

IsSupplementedBy

A Multiscale Electro-Metabolic Model of a Rat Neocortical Circuit Reveals the Impact of Ageing on Central Cortical Layers [dataset]

https://zenodo.org/records/14187063
Available on Infoscience
May 26, 2025
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/250428
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