Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. Tuning passive parameters for each model predicted significantly higher membrane resistance (Rm) in aged versus young neurons. This Rm increase alone did not account for the empirically observed fI-curves, but coupling these Rm values with subtle differences in morphology and membrane capacitance Cm did. The predicted differences in passive parameters (or other parameters with similar effects) are mathematically plausible, but must be tested empirically.
Model Type: Neuron or other electrically excitable cell
Cell Type(s): Neocortex L2/3 pyramidal GLU cell
Currents: I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP
Model Concept(s): Influence of Dendritic Geometry; Detailed Neuronal Models; Action Potentials; Aging/Alzheimer`s
Simulation Environment: NEURON
Implementer(s): Weaver, Christina [christina.weaver at fandm.edu]
References:
Coskren PJ et al. (2015). Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex. Journal of computational neuroscience. 38 [PubMed]