Transcranial magneto-acoustic electrical stimulation (TMAES) is a non-invasive novel neuromodulation technique based on the magneto-acoustic coupling effect. In this study, we employed APP/PS1 transgenic mice as an experimental model, targeting the hippocampus. Cognitive function was assessed through behavioral tests, while neuronal morphology was examined using hematoxylin-eosin and Golgi staining. Additionally, fiber photometry was utilized to measure calcium transient intensity in the CA1 region. By investigating the effects of TMAES on synaptic plasticity in the hippocampus, we aimed to elucidate its potential regulatory mechanisms in improving cognitive function in AD mice. Behavioral results showed that the cognitive and memory abilities of mice in the AD+sham group were significantly lower than those in the WT+sham group, while TMAES intervention could significantly improve the cognitive function of mice in the AD+TMAES group. Morphological detection indicated that the number of pyramidal neurons and the density of dendritic spines in the hippocampal CA1 region of the AD+sham group were decreased, with an increased proportion of immature spines; all the above indicators were significantly improved after TMAES intervention. Fiber photometric detection revealed that the calcium activity and calcium amplitude of neurons in the CA1 region of the AD+TMAES group were significantly enhanced compared with those of the AD+sham group. Pearson correlation analysis showed that cognitive level was positively correlated with calcium amplitude, dendritic spine density, and mature spine proportion. Meanwhile, calcium amplitude was positively correlated with dendritic spine density and mature spine proportion. Therefore, TMAES may alleviate the damage to synaptic plasticity in the hippocampal CA1 region of APP/PS1 mice by regulating the function of calcium ion channels, thereby improving cognitive impairment.
