Glutamic acid stimulation of the perifornical-lateral hypothalamic area promotes arousal and inhibits non-REM/REM sleep

The orexinergic neurons, localized in the perifornical hypothalamic area (PeF), are active during waking and quiet during non-rapid eye movement (non-REM) and REM sleep. Orexins promote arousal and suppress non-REM and REM sleep. Although in vitro studies suggest that PeF-orexinergic neurons are under glutamatergic influence, the sleep–wake behavioral consequences of glutamatergic activation of those neurons are not known. We examined the effects of bilateral glutamatergic activation of neurons in and around the PeF on sleep–wake parameters in freely behaving rats. Nine male Wistar rats were surgically prepared for electrophysiological sleep–wake recording and with bilateral guide cannulae targeting the PeF for microinjection. The sleep–wake profiles of each rat were recorded for 8 h under baseline (without injection), and after bilateral microinjections of 200 nl saline and 200 nl saline containing 20 or 40 ng of l-glutamic acid (GLUT) using a remote-controlled pump and without disturbing the animals. The injection of 40 ng GLUT into the PeF (n = 6) significantly increased mean time spent in waking (F = 85.11, p < 0.001) and concomitantly decreased mean time spent in non-REM (F = 19.67, p < 0.001) and REM sleep (F = 38.72, p < 0.001). The increase in waking and decreases in non-REM and REM sleep were due to significantly increased durations of waking episodes (F = 24.64; p < 0.001) and decreased durations of non-REM (F = 12.96; p = 0.002) and REM sleep events (F = 13.82; p = 0.001), respectively. These results suggest that the activation of neurons in and around the PeF including those of orexin neurons contribute to the promotion of arousal and suppression of non-REM and REM sleep.