Dynamic Analysis of Serotonin-Regulated Neuron–Astrocyte Model for Alzheimer’s Disease

Inspired by the impact of serotonin on Alzheimer’s Disease (AD), the present work proposes a serotonin-regulated neuron–astrocyte model, used to investigate the influence of serotonin 2A (5-HT[Formula: see text]) receptor impairment on the model dynamics and the therapeutic effect of increasing extracellular serotonin levels. First, the density of astrocytic 5-HT[Formula: see text] receptors is reduced to simulate the histopathological phenomenon of 5-HT[Formula: see text] receptor lesions in AD. Combining bifurcation analysis and power spectral analysis, our results indicate that a reduction in the density of 5-HT[Formula: see text] receptors not only decreases the oscillation amplitude and frequency of astrocytic Ca[Formula: see text] but also reduces the relative slow gamma power and firing rate of pyramidal neurons. These simulated results are consistent with physiological experiments in AD mice. Additionally, the impact of decreased 5-HT[Formula: see text] receptors on pyramidal neurons is simulated by increasing the conductivity of calcium ions in pyramidal neurons. The conclusion shows that although increasing the conductivity of calcium ions has a limited effect on the dynamic behavior of astrocytic Ca[Formula: see text], it results in a reduction in the relative slow gamma power and firing rate of pyramidal neurons. Finally, we simulate a therapeutic strategy by inhibiting Serotonin Reuptake Transporters (SERTs). This simulation demonstrates that an increased extracellular serotonin concentration not only restores the oscillation frequency and amplitude of astrocytic Ca[Formula: see text] but also rescues the relative slow gamma power in pyramidal neurons. Our serotonin-incorporated neuron–astrocyte model reveals bifurcation in astrocytic Ca[Formula: see text] dynamics and decreases relative slow gamma power in pyramidal neurons. These phenomena not only replicate experimental findings in AD but also allow us to explore serotonin-based therapeutic strategies, potentially offering new insights for AD treatment.