Deep brain stimulation of the entorhinal cortex modulates CA1 theta-gamma oscillations in mouse models of preclinical Alzheimer's disease

Deep brain stimulation (DBS) is a neuromodulation method that modulates neuronal activity. A trend in the treatment of Alzheimer’s disease (AD) is targeting key points of neural circuits with DBS. Here, we explored the effects of DBS targeted to the entorhinal cortex (EC) on neurons in the hippocampal CA1 in a mouse model of preclinical AD. Specifically, we recorded field potential signals from CA1 in preclinical AD mice after DBS of the EC (1 h/day for 21 days of 100 μA, 90 μs, 10 Hz, biphasic square wave pulse) with in-vivo electrophysiology and evaluated corresponding changes in behavior with the open field task and Morris water maze (MWM) task. We also assessed changes in pathological markers and neurogenesis in the hippocampus with immunohistological staining. DBS of the EC increased theta and gamma power and modulated theta in the high gamma band (50–100 Hz) in preclinical AD mice. After DBS of the EC, these mice performed better in the MWM task and exhibited reduced deposition of beta-amyloid and neuronal changes including significant increases in proliferating neurons and immature neurons. This is the first study to target the EC with DBS and analyze resulting neural oscillations in the hippocampal CA1 in a model of preclinical AD. The findings support the use of DBS as a potential treatment for AD.