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

## TL;DR

This study uses a detailed computational model to show how aging affects energy supply in the brain, particularly in central cortical layers.

## Contribution

A novel multiscale electro-metabolic model of a rat neocortical circuit that captures age-related energy impairments.

## Key findings

- The model shows that neurons with different electrical properties have varying energy demands.
- Middle cortical layers are especially vulnerable to energy deficits during metabolic aging.
- The model effectively captures electro-metabolic coupling at the circuit level.

## Abstract

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.

The brain’s remarkable ability to process information comes at a high energy cost. Neurons, the brain’s communication cells, require substantial energy to send electrical signals to one another and to remain prepared for communication. This energy is provided through a complex partnership between neurons, glial cells, and blood vessels. However, as we age, this system becomes less efficient and struggles to meet the brain’s energy demands. To investigate these processes, we developed a computational model that integrates the electrical activity of neurons with the metabolic functions of surrounding cells and blood vessels. Using a detailed reconstruction of a rat neocortical microcircuit, we examined how energy production and consumption are linked to electrical signalling. Our findings reveal that neurons with different electrical properties have distinct energy requirements, and certain layers of the brain are more susceptible to energy deficits with ageing. This research offers a comprehensive framework for understanding the interplay between electrical activity and metabolism and provides valuable insights into how the brain’s energy supply is affected by ageing, which may guide future studies on age-related cognitive decline or neurological disorders.