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

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.