Early-stage dysfunction of hippocampal theta and gamma oscillations and its modulation of neural network in a transgenic 5xFAD mouse model.

Alzheimer's disease (AD) is pathologically characterized by amyloid-β (Aβ) accumulation, which induces Aβ-dependent neuronal dysfunctions. We focused on the early-stage disease progression and examined the neuronal network functioning in the 5xFAD mice. The simultaneous intracranial recordings were obtained from the hippocampal perforant path (PP) and the dentate gyrus (DG). Concomitant to Aβ accumulation, theta power was strongly attenuated in the PP and DG regions of 5xFAD mice compared to those in nontransgenic littermates. For either theta rhythm or gamma oscillation, the phase synchronization on the PP-DG pathway was impaired, evidenced by decreased phase locking value and diminished coherency index. To alleviate the neural oscillatory deficits in early-stage AD, a neural modulation approach (rTMS) was used to activate gamma oscillations and strengthen the synchronicity of neuronal activity on the PP-DG pathway. In brief, there was a significant neuronal network dysfunction at an early-stage AD-like pathology, which preceded the onset of cognitive deficits and was likely driven by Aβ accumulation, suggesting that the neural oscillation analysis played an important role in early AD diagnosis.