A biophysical minimal model to investigate age-related changes in CA1 pyramidal cell electrical activity

Abstract

Aging is a physiological process that is still poorly understood, especially with respect to effects on the brain. There are open questions about aging that are difficult to answer with an experimental approach. Underlying challenges include the difficulty of recording in vivo single cell and network activity simultaneously with submillisecond resolution, and brain compensatory mechanisms triggered by genetic, pharmacologic, or behavioral manipulations. Mathematical modeling can help address some of these questions by allowing us to fix parameters that cannot be controlled experimentally and investigate neural excitability under different conditions. Previous modeling approaches in the CA1 region of the hippocampus have provided many insights, but have also been limited by an inherent trade-off between physiological accuracy and computational load. Herein, we present a biophysical, minimal model of CA1 pyramidal cells (PCs) based on general expressions for transmembrane transport derived from basic thermodynamical principles. The model allows directly varying the contribution of transmembrane transport proteins by changing their number. By analyzing the dynamics of the model we find parameter ranges that reproduce the variability in electrical activity seen in PCs. In addition, the model explains the dynamics underlying age-related changes in excitability that are qualitatively and quantitatively similar to those observed in aging PCs as caused by increased L-type Ca2+ channel expression.