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Morse TM, Carnevale NT, Mutalik PG, et al. Abnormal Excitability of Oblique Dendrites Implicated in Early Alzheimer's: A Computational Study. Front Neural Circuits. 2010;4doi: 10.3389/fncir.2010.00016.
Morse, T. M., Carnevale, N. T., Mutalik, P. G., Migliore, M., & Shepherd, G. M. (2010). Abnormal Excitability of Oblique Dendrites Implicated in Early Alzheimer's: A Computational Study. Frontiers in neural circuits, 4. https://doi.org/10.3389/fncir.2010.00016
Morse, Thomas M, et al. "Abnormal Excitability of Oblique Dendrites Implicated in Early Alzheimer's: A Computational Study." Frontiers in neural circuits vol. 4 (2010). doi: https://doi.org/10.3389/fncir.2010.00016
Morse TM, Carnevale NT, Mutalik PG, Migliore M, Shepherd GM. Abnormal Excitability of Oblique Dendrites Implicated in Early Alzheimer's: A Computational Study. Front Neural Circuits. 2010 May 31;4. doi: 10.3389/fncir.2010.00016. eCollection 2010. PMID: 20725509; PMCID: PMC2901152.
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Front Neural Circuits. 2010 May 31;4. doi: 10.3389/fncir.2010.00016. eCollection 2010.

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

Frontiers in neural circuits

Thomas M Morse, Nicholas T Carnevale, Pradeep G Mutalik, Michele Migliore, Gordon M Shepherd

Affiliations

  1. Department of Neurobiology, Yale University School of Medicine New Haven, CT, USA.

PMID: 20725509 PMCID: PMC2901152 DOI: 10.3389/fncir.2010.00016

Abstract

The integrative properties of cortical pyramidal dendrites are essential to the neural basis of cognitive function, but the impact of amyloid beta protein (abeta) on these properties in early Alzheimer's is poorly understood. In animal models, electrophysiological studies of proximal dendrites have shown that abeta 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 abeta, 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: action potential backpropagation; computer model; electrical activity

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