Analyzing Hippocampal Neural Dynamics Under Acetylcholine Deficiency Related to Alzheimer's Disease.

Acetylcholine, as an important neurotransmitter, regulates neural excitability and discharge property distinctly, whose deficiency in the hippocampus can deteriorate cognitive and memory functions in Alzheimer's Disease (AD). By establishing a hippocampal small-world network of pyramidal neurons and interneurons, this work aims to explore how acetylcholine deficiency influences the hippocampal neural dynamics from the perspective of neurocomputation. Based on some experimental results that acetylcholine can inhibit several K + channels in the pyramidal neuron via muscarinic receptors, we simulate acetylcholine deficiency by increasing the conductance g M of M-type (or g A of A-type) K + channel. The numerical results indicate that the enhancement of g M or g A can affect the pyramidal neuron dynamics in the individual node and network levels significantly. For the individual pyramidal neuron, its excitability and mean firing rate gradually decrease upon increasing g M or g A , in particular, the neuron transitions from a firing state to a resting state when g M or g A increases over a threshold. Through dynamic bifurcation analysis, we find that the underlying dynamical mechanism behind these changes is attributed to sub-critical Andronov–Hopf or saddle-node bifurcations induced by acetylcholine deficiency. For pyramidal neurons in the network scale, acetylcholine deficiency can shift the network encoding mode from collective regular firing to bursting, and more importantly, the averaged mean firing rate and sample entropy of the network decrease significantly with severe acetylcholine deficiency. These results are consistent with previous studies reported in the electrophysiological experiments of AD. This work may help to deeply understand the AD pathogenesis of cholinergic hypothesis. [ABSTRACT FROM AUTHOR]