Integrated dopamine sensing and 40 Hz hippocampal stimulation improves cognitive performance in Alzheimer’s mouse models
Shiya Lv, Fan Mo, Zhaojie Xu, Yu Wang, Yaoyao Liu, Meiqi Han, Yimin Duan, Luyi Jing, Fanli Kong, Qianli Jia, Ming Li, Wei Xu, Peiyao Jiao, Mixia Wang, Juntao Liu, Jinping Luo, Junbo Wang, Zhongwei Fan, Yilin Song, Yirong Wu, Xinxia Cai
Abstract
Hippocampal degeneration and reduced dopamine levels in Alzheimer’s disease are associated with severe memory and cognitive impairments. However, the lack of multifunctional in situ neural chips has posed challenges for integrated investigations of Alzheimer’s disease pathophysiology, dopamine dynamics, and neural activity. Therefore, we developed NeuroRevive-FlexChip, a flexible neural interface capable of precise electrical modulation and simultaneous in situ monitoring of dopamine levels and neural activity. In this study, the NeuroRevive-FlexChip demonstrates improved electrochemical detection sensitivity and modulation efficiency. Preliminary observations in APP/PS1 mice indicate that implantation of the chip in the hippocampal CA1 region, combined with 40 Hz stimulation, may contribute to the restoration of dopamine release, a reduction in neuronal hyper-synchronization, and a shift toward more stable firing patterns. These effects appear to be modulated by dopamine-related mechanisms. Furthemore, 40 Hz stimulation was observed to correlate with reduction in Aβ42 deposition and modest improvements in spatial cognition performance, as assessed by the Y-maze test. These findings highlight the potential of NeuroRevive-FlexChip as a research tool for investigating the mechanisms of 40 Hz stimulation in Alzheimer’s disease models. Further studies could explore its utility in clarifying the relationship between dopamine dysfunction, neural activity, and amyloid pathology. While these early results are promising, additional preclinical and translational research will be necessary to assess the therapeutic potential of this approach for neurodegenerative diseases. Dopaminergic dysfunction is a key of Alzheimer’s disease pathogenesis. Here, the authors developed a multifunctional neural interface that simultaneously monitors dopamine dynamics and neural activity while delivering 40 Hz stimulation to rescue cognitive deficits in APP/PS1 mice.