Dynamical effects of dendritic pruning implicated in aging and neurodegeneration: Towards a measure of neuronal reserve

Abstract

AbstractAging is a main risk factor for neurodegenerative disorders including Alzheimer’s disease. It is often accompanied by reduced cognitive functions, gray-matter volume, and dendritic integrity. Although age-related brain structural changes have been observed across multiple scales, their functional implications remain largely unknown. Here we simulate the aging effects on neuronal morphology as dendritic pruning and characterize its dynamical implications. Utilizing a minimal computational modeling approach, we simulate the dynamics of detailed digitally reconstructed pyramidal neurons of humans obtained from the online repository Neuromorpho.org. We show that as aging progressively affects neuronal integrity, neuronal firing rate is reduced, which causes a reduction in energy consumption, energy efficiency, and dynamic range. Pruned neurons require less energy but their function is often impaired, which can explain the diminished ability to distinguish between similar experiences (pattern separation) in older people. Our measures indicate that the resilience of neuronal dynamics is neuron-specific, heterogeneous, and strongly affected by dendritic topology and the centrality of the soma. Based on the emergent neuronal dynamics, we propose to classify the effects of dendritic deterioration, and put forward that soma centrality measures neuronal reserve. Moreover, our findings suggest that increasing dendritic excitability could partially mitigate the dynamical effects of aging.