The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging.

Whereas neuronal numbers are largely preserved in normal aging, subtle morphological changes occur in dendrites and spines, whose electrotonic consequences remain unexplored. We examined age-related morphological alterations in 2 types of pyramidal neurons contributing to working memory circuits in the macaque prefrontal cortex (PFC): neurons in the superior temporal cortex forming "long" projections to the PFC and "local" projection neurons within the PFC. Global dendritic mass homeostasis, measured by 3-dimensional scaling analysis, was conserved with aging in both neuron types. Spine densities, dendrite diameters, lengths, and branching complexity were all significantly reduced in apical dendrites of long projection neurons with aging, but only spine parameters were altered in local projection neurons. Despite these differences, voltage attenuation due to passive electrotonic structure, assuming equivalent cable parameters, was significantly reduced with aging in the apical dendrites of both neuron classes. Confirming the electrotonic analysis, simulated passive backpropagating action potential efficacy was significantly higher in apical but not basal dendrites of old neurons. Unless compensated by changes in passive cable parameters, active membrane properties, or altered synaptic properties, these effects will increase the excitability of pyramidal neurons, compromising the precisely tuned activity required for working memory, ultimately resulting in age-related PFC dysfunction.