Different correlation patterns between EEG and memory after E/I balance adjustment in normal middle-aged mice and AD model mice

Alzheimers disease (AD) is correlated with brain atrophy, neuronal loss, neurotransmitter imbalance, and cognitive decline, which also occur in normal aging. Thus, comparing the differences between normal aging and AD is of interest in order to test the accelerated aging hypothesis of AD. An imbalance between excitatory/inhibitory (E/I) neurotransmission, especially in gamma-aminobutyric acid (GABA) inhibition dysfunction, is involved in both AD and normal aging. In the present study, we performed correlation analyses between electroencephalograms (EEGs) and memory in middle-aged ([~]12 months old) wild-type mice (WT) and AD model mice (APP/PS1) after E/I balance adjustment via GABAA agonist muscimol and antagonist bicuculline administration (0.1 mg/kg intraperitoneally). Specifically, EEGs of the hippocampus and prefrontal cortex were recorded during Y-maze performance. Overall, WT and AD mice showed different correlation patterns between EEG activity and behavioral memory performance. Significant correlations were observed in EEG activity across a wider range of frequency bands (2-100 Hz, except 4-8 Hz) in WT mice, but were mainly observed in low frequency bands (delta-theta, 2-8 Hz) in AD mice. In addition, muscimol and bicuculline treatment contributed to better brain function in AD mice; in contrast, bicuculline administration resulted in poorer brain function in WT mice. Thus, our study suggests that AD shows a distinct pattern of disrupted brain function, rather than accelerated aging. Importantly, this work reveals new insights into future AD treatment by influencing low-frequency EEG activity through E/I balance adjustment, thereby aiding cognitive recovery.