Impact of age-related dendritic atrophy on evoked electrophysiological activity in neocortical layer 3 pyramidal neurons: a modeling study

With aging that is often accompanied by neurodegenerative disorders, morphological atrophy and abnormal changes in excitability progress in central neurons. Cellular mechanisms, which relate to the morphological and physiological features of aging neurons, remain poorly understood, partly due to methodological and ethical constraints hampering clinical and experimental studies. Computation experiments on biologically accurate models have become increasingly widespread complementary sources of data shading light on such mechanisms. In this work, we used a model of neocortical layer 3 pyramidal neuron with reconstructed dendritic arborization and reproduced the age-related morphological atrophy by virtual pruning of dendrites and reducing the dendritic spine density to a smaller or greater extent. The changes in the intrinsic electrical excitability of simulated cells were characterized by changes in the responses to a somatically applied depolarization current. With each destructive morphological alteration, doublet bursting observed in the intact neuron has changed for continuous spiking of a greater rate associated with greater dendrite atrophy. The observed firing patterns were basically like those earlier described for simulated atrophic hippocampal neurons having different overall dendritic morphology as well as biophysical properties and distribution of type-specific ion channels.