Changes in sensorimotor cortex oscillatory activity by orexin‐A in the ventrolateral preoptic area of the hypothalamus reflect increased muscle tone

Abstract

Orexin-A (OXA) is a hypothalamic neuropeptide implicated in the regulation of wakefulness, appetite, reward processing, muscle tone, motor activity, and other physiological processes. The broad range of systems affected stems from the widespread projections of orexin neurons toward multiple brain regions regulating numerous physiological processes. Orexin neurons integrate nutritional, energetic, and behavioral cues and modulate the functions of target structures. Orexin promotes spontaneous physical activity (SPA), and we recently showed that orexin injected into the ventrolateral preoptic area (VLPO) of the hypothalamus increases behavioral arousal and SPA in rats. However, the specific mechanisms underlying the role of orexin in physical activity are unknown. Here we tested the hypothesis that OXA injected into the VLPO alters the oscillatory activity in the electroencephalogram (EEG) to reflect an increased excitability of the sensorimotor cortex, which may explain the associated increase in SPA. The results showed that OXA increased wakefulness following injections into the VLPO. In addition, OXA altered the power spectrum of the EEG during the awake state by decreasing the power of 5-19 Hz oscillations and increasing the power of >35 Hz oscillations, which are markers of increased sensorimotor excitability. Consistently, we found that OXA induced greater muscle activity. Furthermore, we found a similar change in power spectrum during slow-wave sleep, which suggests that OXA altered the EEG activity in a fundamental way, even in the absence of physical activity. These results support the idea that OXA increases the excitability of the sensorimotor system, which may explain the corresponding increase in awake time, muscle tone, and SPA.

Interactions between Lateral Hypothalamic Orexin and Dorsal Raphe Circuitry in Energy Balance

“…However, in the current study, orexin DRN enhanced SPA only during the first hour post injection, ruling out any effect of central fatigue in our study. In addition, we have recently demonstrated that the central injection of orexin enhances the excitability of the motor system in the brain [116], suggesting that DRN orexin-induced enhancement SPA may result from heightened brain motor preparedness. Overall, 5HT signaling has a complex role in the modulation of motor behavior and the current data suggest that the orexin-DRN pathway positively modulates SPA.…”