THALAMOCORTICAL CONNECTIVITY AND SLEEP DISRUPTION IN ALZHEIMER'S DISEASE: CORRELATIONS WITH COGNITIVE DEFICITS

A degraded sleep is a characteristic of neurodegenerative disorders, notably in Alzheimer's disease (AD). Sleep stability is crucial for the elimination of brain toxins, including Tau and β-amyloid, as well as for memory consolidation, attention, and overall cognitive function. Its stability relies on brain oscillations regulated by thalamocortical interactions. The aim of this study is to longitudinally track the evolution of sleep quality, thalamocortical connectivity, and cognitive functions in a murine model of AD. APP/PS1-21 mice and control littermates were evaluated monthly from 3 to 12 months old. Sleep fragmentation and sleep oscillation occurrence were examined thanks to six stereo-electrodes implanted in diverse brain regions. Thalamocortical connectivity was tested through optogenetic stimulations in the midline thalamus (rhomboid). Long-term memory and impulsivity were assessed using the cheeseboard maze and the Free Feeding Device, respectively. Our analyses suggest that thalamocortical connectivity increase in AD mice between 3 and 6 months old, then progressively decreases with aging, which could reflect an initial hyperactivity followed by connectivity loss, while control mice show minimal changes. AD mice also tend to exhibit more microarousals than controls during the light phase from 6 months of age. Behavioral data indicate that AD mice show increased impulsivity around 7 months of age and develop long-term memory deficits compared to WT mice at approximately 9 months old. Although these results need to be confirmed, they support the hypothesis that thalamocortical connectivity changes precede sleep disruption and cognitive deficits in pathological mice.