title: Computational study of hippocampal-septal theta rhythm changes due to β-amyloid-altered ionic channels.
abstract: Electroencephagraphy (EEG) of many dementia patients has been characterized by an increase in low frequency field potential oscillations. One of the characteristics of early stage Alzheimer's disease (AD) is an increase in theta band power (4-7 Hz). However, the mechanism(s) underlying the changes in theta oscillations are still unclear. To address this issue, we investigate the theta band power changes associated with β-Amyloid (Aβ) peptide (one of the main markers of AD) using a computational model, and by mediating the toxicity of hippocampal pyramidal neurons. We use an established biophysical hippocampal CA1-medial septum network model to evaluate four ionic channels in pyramidal neurons, which were demonstrated to be affected by Aβ. They are the L-type Ca²⁺ channel, delayed rectifying K⁺ channel, A-type fast-inactivating K⁺ channel and large-conductance Ca²⁺-activated K⁺ channel. Our simulation results demonstrate that only the Aβ inhibited A-type fast-inactivating K⁺ channel can induce an increase in hippocampo-septal theta band power, while the other channels do not affect theta rhythm. We further deduce that this increased theta band power is due to enhanced synchrony of the pyramidal neurons. Our research may elucidate potential biomarkers and therapeutics for AD. Further investigation will be helpful for better understanding of AD-induced theta rhythm abnormalities and associated cognitive deficits.
authors: Intelligent Systems Research Centre, University of Ulster Magee Campus, Derry, Northern Ireland, United Kingdom. x.zou@ulster.ac.uk
authors: Xin
authors: X
authors: Zou
authors: Damien
authors: D
authors: Coyle
authors: Kongfatt
authors: K
authors: Wong-Lin
authors: Liam
authors: L
authors: Maguire
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D003198:Computer Simulation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D020665:Septum of Brain / Q000187:drug effects* / Q000502:physiology*; D013826:Theta Rhythm / Q000187:drug effects / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D007473:Ion Channels