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

Abstract

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 8h under baseline (without injection), and after bilateral microinjections of 200nl saline and 200nl saline containing 20 or 40ng of l-glutamic acid (GLUT) using a remote-controlled pump and without disturbing the animals. The injection of 40ng 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.