Electrical stimulation of the rostral ventrolateral medulla promotes wakefulness in rats

Abstract

Objectives: Previous studies suggest that central sympathetic activity might carry information on wakefulness, so we tested the hypothesis that direct activation of the rostral ventrolateral medulla (RVLM), a well-studied sympathetic vasomotor center, promotes wakefulness.

Methods: A bipolar stimulating electrode was implanted in the right RVLM of Wistar-Kyoto rats or in a brainstem control site. Bioelectrical signals were recorded using a telemetry system. The experiment comprised a baseline session and a 6-h electrical stimulation session (50 μA, 50 Hz for 3 min every 20 min). Sleep-wake stages were defined by the electroencephalogram (EEG) and electromyogram (EMG) as active waking (AW), nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Autonomic function was assessed using cardiovascular variability analysis.

Results: During the RVLM stimulation session, AW time increased from 38.48±5.82 to 99.91±8.23 min compared with baseline (P<.001), while REM sleep was decreased from 110.10±4.91 to 50.74±13.01 min (P=.004). Analysis of the RVLM stimulation bouts delivered during NREM sleep showed a significantly higher probability of awakening; it also showed that the latency to arousal was significantly shorter than the latency for 10% blood pressure (BP) increase (1.50±0.30 vs 7.42±1.83 s; P=.009).

Conclusions: Our findings show that direct stimulation of the RVLM promotes wakefulness, suggesting that sleep disturbance may result from central sympathetic activation.

Keywords: Arousal; Electrical stimulation; Heart rate variability; Rostral ventrolateral medulla; Sleep; Sympathetic nervous system.