Dynamic analysis of hippocampal tripartite synapse model under acetylcholine deficiency related to Alzheimer's disease
摘要
Acetylcholine deficiency, the primary pathological manifestation of the late-stage Alzheimer's disease (AD), may lead to abnormalities in tripartite synapse, yet the dynamical mechanism remains unclear. To investigate how acetylcholine deficiency alters tripartite synapse dynamics, we propose a hippocampal tripartite synapse model of a pyramidal neuron, an interneuron and an astrocyte regulated by acetylcholine. The numerical results show that acetylcholine deficiency acting on pyramidal neuron or interneuron can reduce the mean firing rate and weaken the astrocyte calcium oscillation, which are consistent with the experimental results in the late-stage AD. Meanwhile, the firing pattern of pyramidal neuron shifts from regular firing to bursting. More importantly, acetylcholine deficiency on astrocyte induces the interesting effects on pyramidal neuron by reducing astrocyte calcium oscillation: when neurons are not or minimally affected by acetylcholine deficiency, acetylcholine deficiency on astrocyte has almost no effect on neuronal firing; when neurons are moderately disturbed by acetylcholine deficiency, acetylcholine deficiency on astrocyte causes pyramidal neuron to recover from bursting to regular firing, accompanied by an increase in mean firing rate; when neurons are greatly disturbed by acetylcholine deficiency, acetylcholine deficiency on astrocyte aggravates neuronal abnormalities. These findings shed light on the dynamics of how neurons interact with astrocytes during the progression of acetylcholine loss in AD. These results can provide more valuable theoretical guidance for the targeted therapy of neurons and astrocytes, so as to formulate more accurate treatment strategies for AD.