Abnormal excitability of oblique dendrites implicated in early Alzheimer's: a computational study
Open Access
- 1 January 2010
- journal article
- Published by Frontiers Media SA in Frontiers in Neural Circuits
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.Keywords
This publication has 58 references indexed in Scilit:
- Learning and aging related changes in intrinsic neuronal excitabilityFrontiers in Aging Neuroscience, 2010
- Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive agingFrontiers in Aging Neuroscience, 2010
- Synapse Distribution Suggests a Two-Stage Model of Dendritic Integration in CA1 Pyramidal NeuronsNeuron, 2009
- Rapid, Bidirectional Remodeling of Synaptic NMDA Receptor Subunit Composition by A-type K+ Channel Activity in Hippocampal CA1 Pyramidal NeuronsNeuron, 2008
- Altered synaptic and non‐synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout miceThe Journal of Physiology, 2008
- Associative pairing enhances action potential back‐propagation in radial oblique branches of CA1 pyramidal neuronsThe Journal of Physiology, 2007
- Dendritic signals from rat hippocampal CA1 pyramidal neurons during coincident pre‐ and post‐synaptic activity: a combined voltage‐ and calcium‐imaging studyThe Journal of Physiology, 2007
- Model Structure Analysis in NEURONPublished by Springer Science and Business Media LLC ,2007
- Zinc-induced aggregation of Aβ (10–21) potentiates its action on voltage-gated potassium channelBiochemical and Biophysical Research Communications, 2006
- The hippocampus: Organizational patterns in health and senescenceMechanisms of Ageing and Development, 1979