Experimental neurology · 2026
40 Hz-rTMS modulates spike-LFP coupling and improves cognitive function in 5xFAD mice.
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Ma Qianhui, Ding Zixiang, Wang Ruru, Jin Jingna, Wang He, Li Ying, Liu Zhipeng, Wang Xin, Yin Tao
Аннотация
OBJECTIVE: Spike-local field potential (LFP) coupling plays a pivotal role in mediating cross-scale neural communication. Although abnormal coupling has been reported in Alzheimer's disease (AD) models in vitro, in vivo evidence remains lacking. This study aimed to characterize in vivo spike-LFP coupling in 5XFAD mice and investigate whether 40 Hz repetitive transcranial magnetic stimulation (rTMS) can ameliorate related deficits.
METHODS: We performed chronic in vivo electrophysiological recordings of spikes and LFPs were performed in the hippocampal dentate gyrus (DG) via. Phase-locking and coherence analysis were employed to quantify spike-LFP coupling. Cognitive function was evaluated using the Y-maze, novel object recognition, and Morris water maze tasks. The correlation between spike-LFP coupling and cognitive performance was analyzed by the Spearman method.
RESULTS: In wild-type (WT) sham mice, DG spikes exhibited tightly confined phase preferences (θ oscillation: 108°-126°; high γ (Hγ) oscillation: 198°-216°). In contrast, 5XFAD mice displayed severely dispersed spike-phase distributions and reduced coupling intensity, with mean vector length decreasing by 19.90% (spike-θ) and 23.8% (spike-Hγ) compared with that in WT-sham controls. Following 14 consecutive days of 40 Hz rTMS intervention, 5XFAD mice exhibited significant increases in mean vector length (θ: +39.44%; Hγ: +31.47%) and normalized spike-LFP phase distributions. Notably, rTMS treatment also markedly rescued learning, memory, and cognitive flexibility in 5XFAD mice. Spike-LFP coupling strength was significantly correlated with learning and memory performance.
CONCLUSION: These preliminary findings suggest that 40 Hz rTMS modulates pathological spike-LFP coupling in 5XFAD mice, laying the groundwork for therapeutic exploration.
METHODS: We performed chronic in vivo electrophysiological recordings of spikes and LFPs were performed in the hippocampal dentate gyrus (DG) via. Phase-locking and coherence analysis were employed to quantify spike-LFP coupling. Cognitive function was evaluated using the Y-maze, novel object recognition, and Morris water maze tasks. The correlation between spike-LFP coupling and cognitive performance was analyzed by the Spearman method.
RESULTS: In wild-type (WT) sham mice, DG spikes exhibited tightly confined phase preferences (θ oscillation: 108°-126°; high γ (Hγ) oscillation: 198°-216°). In contrast, 5XFAD mice displayed severely dispersed spike-phase distributions and reduced coupling intensity, with mean vector length decreasing by 19.90% (spike-θ) and 23.8% (spike-Hγ) compared with that in WT-sham controls. Following 14 consecutive days of 40 Hz rTMS intervention, 5XFAD mice exhibited significant increases in mean vector length (θ: +39.44%; Hγ: +31.47%) and normalized spike-LFP phase distributions. Notably, rTMS treatment also markedly rescued learning, memory, and cognitive flexibility in 5XFAD mice. Spike-LFP coupling strength was significantly correlated with learning and memory performance.
CONCLUSION: These preliminary findings suggest that 40 Hz rTMS modulates pathological spike-LFP coupling in 5XFAD mice, laying the groundwork for therapeutic exploration.