Theta wave bursts during rapid-eye-movement sleep and cataplexy in hypocretin-deficient narcoleptic mice

Hypothalamic hypocretin (HCRT) neurons modulate wake-sleep behavior and autonomic functions, and their loss entails narcolepsy. In HCRT-deficient narcoleptic mice, high-amplitude and phasic electroencephalographic (EEG) bursts have been described during rapid-eye-movement sleep (REMS) and cataplexy and interpreted as temporally displaced sleep spindles. We tested this interpretation by performing a detailed quantitative analysis of these phasic EEG events. Twenty HCRT-deficient mice and 15 wild-type controls were implanted with EEG and electromyographic electrodes and a telemetric blood pressure transducer. Data were analyzed with Chi-Square, Mann-Whitney e Wilcoxon tests and significance at P < 0.05. 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. Similar EEG events were detected in a significantly lower fraction (27%) of wild-type mice and with a significantly lower occurrence rate (0.8 vs. 5 per hour of REMS). Theta bursts were significantly more likely to occur during the dark period and in the last third of REMS episodes, and were not associated with any significant cardiovascular change. The frequency and pattern of occurrence of theta bursts are not compatible with sleep spindles. Thus, theta wave bursts may represent a novel neurophysiological abnormality associated with HCRT deficiency.