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

Zou, Xin, Coyle, Damien, Wong-Lin, KongFatt and Maguire, Liam (2012) Beta-amyloid induced changes in A-type K+ current can alter hippocampo-septal network dynamics. Journal of Computational Neuroscience, 32 (3). pp. 465-477. [Journal article]

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URL: http://www.springerlink.com/content/f195565882572n41/

DOI: 10.1007/s10827-011-0363-7

Abstract

Alzheimer's disease (AD) progression is usually associated with memory deficits and cognitive decline. A hallmark of AD is the accumulation of beta-amyloid (Aβ) peptide, which is known to affect the hippocampal pyramidal neurons in the early stage of AD. Previous studies have shown that Aβ can block A-type K(+) currents in the hippocampal pyramidal neurons and enhance the neuronal excitability. However, the mechanisms underlying such changes and the effects of the hyper-excited pyramidal neurons on the hippocampo-septal network dynamics are still to be investigated. In this paper, Aβ-blocked A-type current is simulated, and the resulting neuronal and network dynamical changes are evaluated in terms of the theta band power. The simulation results demonstrate an initial slight but significant theta band power increase as the A-type current starts to decrease. However, the theta band power eventually decreases as the A-type current is further decreased. Our analysis demonstrates that Aβ blocked A-type currents can increase the pyramidal neuronal excitability by preventing the emergence of a steady state. The increased theta band power is due to more pyramidal neurons recruited into spiking mode during the peak of pyramidal theta oscillations. However, the decreased theta band power is caused by the spiking phase relationship between different neuronal populations, which is critical for theta oscillation, is violated by the hyper-excited pyramidal neurons. Our findings could provide potential implications on some AD symptoms, such as memory deficits and AD caused epilepsy.

Item Type:Journal article
Keywords:Alzheimer’s disease – β-Amyloid – A-type K+ current – Phase-plane analysis – Hippocampo-septal theta rhythm
Faculties and Schools:Faculty of Computing & Engineering
Faculty of Computing & Engineering > School of Computing and Intelligent Systems
Research Institutes and Groups:Computer Science Research Institute > Intelligent Systems Research Centre
Computer Science Research Institute
ID Code:20123
Deposited By: Dr Kongfatt Wong-Lin
Deposited On:29 Sep 2011 10:28
Last Modified:09 Dec 2015 10:59

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