Impaired hippocampal-cortical coupling but preserved local synchrony during sleep in APP/PS1 mice modeling Alzheimer's disease.

Sleep, in addition to its brain restorative processes, plays an important role in memory transfer from its temporary store in the hippocampus to the more permanent storage in the neocortex. Alzheimer's disease (AD) affects memory and sleep. The aim of this study was to explore disturbances in global and local synchrony patterns between brain regions in the APP/PS1 mouse model of the AD during natural sleep. We used 8 male APPswe/PS1dE9 mice and 6 wild-type littermates, aged 5-6 months, with multiple electrode bundles implanted into cortical regions, thalamus and hippocampus. We measured video-EEG in freely moving animals and analyzed synchrony during NREM vs REM sleep. Global synchrony between medial frontal cortex and hippocampus measured with magnitude-squared coherence was slightly decreased in delta range during NREM stage of sleep in APP/PS1 mice. In contrast, local hippocampal synchrony measured with cross-frequency coupling remained intact. Ripple structure or frequency did not differ between the genotypes. However, the coupling of the spindle-band power peak in the medial prefrontal cortex to hippocampal ripples was significantly decreased compared to wild-type animals. The delicate timing of hippocampal ripples, frontal delta, and corticothalamic spindle oscillations may be the first sign of impaired memory in amyloid plaque-forming transgenic mice.