0296 Human Tau-related Impairment Of Sleep Spindle-slow Oscillation Coupling In The PS19 Mouse Model Of Tauopathy. (12th April 2019) - Kam, Korey
Abstract: Introduction: Sleep spindles and slow oscillations (SOs) are associated with cognitive function, and their temporal coupling decreases with aging in humans. The current work examines the impact of neurofibrillary tau tangles (NFTs) and cortical degeneration on both spindle density and spindle-SO coupling with aging in a mouse model of tauopathy. Methods: PS19 mice (MAPT P301S) (3 male, 3 female) and non-transgenic littermates (3 male, 3 female) were implanted with EEG electrodes targeted over bilateral anterior cortex. Twenty-four hour recordings (12/12hr Light:Dark cycle) were performed at 2 months, when little to no overt tau pathology is present, and 10 months, when tau hyperphosphorylation and NFT's are present throughout many cortical and brainstem areas. Sleep and wake were scored manually, spindles (10-16 Hz) were detected with an automated algorithm, and their phase within cortical slow oscillations (<1 Hz) was determined. Results: Significantly greater spindle density was observed in 2mo PS19 mice (3.9±0.4/min NREM) compared to 2mo non-transgenic littermates (5.8±0.4/min. NREM, t-test, p=0.007). This genotype difference was not observed at 10 months (PS19: 4.0±0.8/min NREM vs controls: 4.8±0.8/min NREM, t-test, p=0.491). Phase coupling of spindles to SOs was significantly reduced in 10 month PS19 mice (mean resultant vector length (MRVL)=0.029±0.004) compared to 10 month controls (MRVL=0.048±0.006, paired t-test, p=0.032). This difference was not observed in younger 2 month old mice. Additionally, we did not observe a significant difference at either age in other spindle biophysical properties such as spindle peak frequency, duration, relative power in the spindle band (10-16 Hz), or in cross-hemispheric synchrony metrics such as spindle coherence, imaginary coherency, or granger causality. Conclusion: PS19 mice manifest an increase in spindle density at age 2 months that normalizes to control levels by age 10 months. Although spindle density is equivalent at age 10 months in PS19 and control mice, coupling of spindles to cortical slow oscillations is significantly reduced in PS19 mice at this age. Support (If Any): NA