Acute Deep Brain Stimulation Induces Sustained Changes in Theta and Gamma Oscillations in Alzheimer's Disease Model Mice.

Abstract

Hippocampal theta and gamma oscillations degenerate early in Alzheimer's disease (AD), and may be a critical pathogenic factor and therapeutic target for AD. Deep brain stimulation (DBS) improves abnormal theta and gamma oscillations in AD; however, how these oscillations dynamically change after stimulation remains unclear. Exploring the prolonged neuroregulatory effects of DBS is essential for optimizing parameters and treatment strategies. Therefore, we investigated the sustained changes in the theta and gamma oscillations of the hippocampal cornu ammonis 1 region induced by acute DBS of the entorhinal cortex in APP/PS1 model mice and explored the underlying mechanisms. The results showed that the theta (4-8 Hz), low gamma (30-50 Hz) and high gamma (50-100 Hz) power of DBS-treated APP/PS1 mice exhibited a dynamic increase-decrease-increase trend, and the modulation index of theta and high gamma increased significantly and persisted for three weeks after DBS. Compared with the pre-DBS state, the firing rates of interneurons in APP/PS1 mice decreased significantly, while those of pyramidal neurons increased significantly, and the mean vector lengths of pyramidal neurons and interneurons with theta and gamma oscillations decreased significantly. Furthermore, the expression of CaMKII- $\alpha $ and GAD67 increased significantly. These findings suggest that acute DBS targeting the entorhinal cortex induces compensatory changes in the power of theta and gamma oscillations in APP/PS1 mice potentially by regulating the neuronal excitatory/inhibitory balance, thereby improving neuronal information transmission.