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

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.

Cluster-permutation statistical analysis for high-dimensional brain-wide functional connectivity mapping

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Study on the Complex Neuron Model’s Reduction and Its Dynamic Characteristics

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“…When the stimulation current gradually increases from zero, the discharge pattern of the two-dimensional reduced neuron model described by formula (9) can change from the resting state to the continuous discharge state. During the process, the neuron model undergoes the dynamic bifurcation.…”

“…Depending on electrophysiological experiments and new technologies such as optics imaging, some models of hippocampal pyramidal neuron based on ionic conductance have been successfully constructed [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. The hippocampal CA1 pyramid neuron [11] generates frequent discharge actions.…”

Biophysical basis of alpha rhythm disruption in Alzheimer’s disease

“…This suggests decreased amount of HCN channels could be an 106 upstream event to Aβ production in AD neurons. There might lie an explanation of 107 observed mild cognitive decline even before more prominent markers associated with 108 AD like Aβ and Neurofibrillary Tangles(NFT) are seen [19]. We systematically explore 109 the conseqeunce of reduced HCN channel activity on Alpha and its rescued by increased 110 cholinergic activity.…”