Abnormal Excitability of Oblique Dendrites Implicated in Early Alzheimer's: A Computational Study

The integrative properties of cortical pyramidal dendrites are essential to the neural basis of cognitive function, but the impact of amyloid beta protein (aβ) on these properties in early Alzheimer's is poorly understood. In animal models, electrophysiological studies of proximal dendrites have shown that aβ induces hyperexcitability by blocking A-type K+ currents (I(A)), disrupting signal integration. The present study uses a computational approach to analyze the hyperexcitability induced in distal dendrites beyond the experimental recording sites. The results show that back-propagating action potentials in the dendrites induce hyperexcitability and excessive calcium concentrations not only in the main apical trunk of pyramidal cell dendrites, but also in their oblique dendrites. Evidence is provided that these thin branches are particularly sensitive to local reductions in I(A). The results suggest the hypothesis that the oblique branches may be most vulnerable to disruptions of I(A) by early exposure to aβ, and point the way to further experimental analysis of these actions as factors in the neural basis of the early decline of cognitive function in Alzheimer's.