Partial lesions of hypocretin neurons of the rat lateral hypothalamus affect wake and sleep regulation under increased sleep pressure

Abstract

Hypocretin(orexin)-producing neurons in the lateral hypothalamic area are important for sleep and wake regulation in mammals and their damage in humans manifests clinically as narcolepsy. While in previous studies experimentally induced massive loss of these neurons revealed their physiological importance, small lesions and their manifestations can uncover more subtle features of sleep regulation and help understand the delicate processes in early stages of pathogenesis of narcolepsy. We studied the effects of partial lesions (approximately 30%) of hypocretin producing neurons in the lateral hypothalamus on sleep patterns and EEG in rats. The lesions did not change the normal sleep and wake pattern in undisturbed rats. The effects of lesions manifested under increased sleep pressure after six hours of sleep deprivation, when they led to accelerated dynamics of compensatory slow wave sleep. The lesions also led to a slight decrease in theta frequency in wakefulness and in REM sleep, which we observed during undisturbed sleep and wake behavior as well as after sleep deprivation.