文章基本信息

标题：Single-neuron dynamical effects of dendritic pruning implicated in aging and neurodegeneration: towards a measure of neuronal reserve
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作者：Christoph Kirch ; Leonardo L. Gollo
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2021
卷号：11
期号：1
页码：1309
DOI：10.1038/s41598-020-78815-z
出版社：Springer Nature
摘要：Aging 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 detailed computational modeling approach, we simulate the dynamics of digitally reconstructed neurons obtained from Neuromorpho.org. We show that dendritic pruning affects neuronal integrity: firing rate is reduced, causing 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 position of the soma. Based on the emergent neuronal dynamics, we propose to classify the effects of dendritic deterioration, and put forward a topological measure of “neuronal reserve” that quantifies the resilience of neuronal dynamics to dendritic pruning. Moreover, our findings suggest that increasing dendritic excitability could partially mitigate the dynamical effects of aging.