Abnormal excitability of oblique dendrites implicated in early Alzheimer's: a computational study

Abstract

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 (IA), 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 IA. The results suggest the hypothesis that the oblique branches may be most vulnerable to disruptions of IA 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.

Beta-amyloid induced changes in A-type K+ current can alter hippocampo-septal network dynamics

“…In our previous work, we have evaluated various ionic channels in the hippocampal pyramidal neurons, which have been reported to be affected by Aβ. Specifically, changes in I Ca , I A , I K and I CT have been evaluated and we found that only Aβ-blocked I A has induced a significant theta band power change (Zou et al 2011), probably due to the increased pyramidal neuronal excitability (Morse et al 2010). In this paper, a wider range of model parameters of I A will be explored and the corresponding theta band power changes will be evaluated.…”

Twenty years of ModelDB and beyond: building essential modeling tools for the future of neuroscience

“…Deterministic approximations allow examining reaction-diffusion dynamics in whole dendrites (e.g., Calcium Waves in Neymotin et al 2015; ModelDB 168874). Single cell models allow investigating the effects of modulators on the electrophysiology of individual neurons (e.g., Morse et al 2010; ModelDB 87284 explores the early effects of amyloid beta on a CA1 pyramidal neuron). Another class of single cell models focuses on gene expression (e.g., circadian rhythms in the suprachiasmatic nucleus of the brain, Kim and Forger 2012; ModelDB 145801).…”

“…A typical morphologically detailed single neuron model (modeldb.yale.edu/87284; Morse et al 2010). (A) A traced neuron (NeuroMorpho.Org c91662) is discretized into many (here 974) compartments.…”

“…(D) The model makes a prediction; here: peak calcium concentration increases in the presence of IA block (thick lines), but the locations of the peaks are independent of IA blockade. Adapted from Morse et al 2010; used by permission.…”

“…(16) View pane for the currently selected file. The readme file for model 87284 (Morse et al; 2010) is shown; modeldb.yale.edu/87284. (C) The Model Views tab displays a graphical representation of the model structure.…”