β oscillation during slow wave sleep and rapid eye movement sleep in the electroencephalogram of a transgenic mouse model of Huntington's disease.

Abstract

STUDY OBJECTIVES: To search for early abnormalities in electroencephalogram (EEG) during sleep which may precede motor symptoms in a transgenic mouse model of hereditary neurodegenerative Huntington's disease (HD). DESIGN: In the R6/1 transgenic mouse model of HD, rhythmic brain activity in EEG recordings was monitored longitudinally and across vigilance states through the onset and progression of disease. MEASUREMENTS AND RESULTS: Mice with chronic electrode implants were recorded monthly over wake-sleep cycles (4 hours), beginning at 9-11 weeks (presymptomatic period) through 6-7 months (symptomatic period). Recording data revealed a unique β rhythm (20-35 Hz), present only in R6/1 transgenic mice, which evolves in close parallel with the disease. In addition, there was an unusual relationship between this β oscillation and vigilance states: while nearly absent during the active waking state, the β oscillation appeared with drowsiness and during slow wave sleep (SWS) and, interestingly, strengthened rather than dissipating when the brain returned to an activated state during rapid eye movement (REM) sleep. CONCLUSIONS: In addition to providing a new in vivo biomarker and insight into Huntington's disease pathophysiology, this serendipitous observation opens a window onto the rarely explored neurophysiology of the cortico-basal ganglia circuit during SWS and REM sleep.