High-amplitude theta wave bursts during REM sleep and cataplexy in hypocretin-deficient narcoleptic mice

Neurons that release hypocretin (HCRT; orexin) peptides control wake-sleep states and autonomic functions, and are lost in patients with narcolepsy with cataplexy. Bursts of high-amplitude electroencephalographic (EEG) activity have been reported during behavioural arrests and rapid eye movement sleep (REMS) episodes at sleep onset in HCRT-deficient narcoleptic mice. Quantitative information on these EEG phenomena is lacking. We aimed to quantify EEG frequency, occurrence rate, daily rhythm and cardiovascular correlates of high-amplitude EEG bursts during REMS and cataplexy. Twenty HCRT-deficient mice and 15 congenic wild-type controls were instrumented with electrodes for sleep recordings and a telemetric blood pressure transducer. Short (1-2 s) high-amplitude bursts of pointed theta waves (7 Hz) occurred during either REMS or cataplexy in 80% of HCRT-deficient mice without any significant accompanying modification in systolic blood pressure or heart period. Theta bursts were significantly more likely to occur during the dark period and in the last third of REMS episodes. Similar EEG events were detected in a significantly lower fraction (27%) of wild-type mice and with a significantly lower occurrence rate (0.8 versus 5 per hour of REMS). These data demonstrate that occurrence of high-amplitude theta bursts is facilitated during REMS and cataplexy in narcoleptic mice. Analysis of EEG frequency and daily and intra-episode patterns of event occurrence do not support interpretation of theta bursts as temporally displaced pre-REMS spindles. Facilitation of high-amplitude theta bursts may thus represent a novel neurophysiological abnormality associated with chronic HCRT deficiency.