Anatomical correlates of the lateral hypothalamic influence on waking-sleep relationship in the rat.

Restricted electrolytic lesions of the lateral hypothalamus (LH) evoke sleeplessness in the rat. The present study was aimed to analyze a possible anatomical substrate of the LH hyposomnia within the hypothalamus. In a group of electrolytically lesioned LH rats the intensity of sleep disturbances, assessed on the basis of EEG records from the neocortex and the hippocampus, was confronted with the localization and the extent of destruction of the LH area and with the topography of known fiber systems of the medical forebrain bundle (MFB). In separate experiments the effects of the destruction of LH cell bodies by means of bilateral ibotenic acid (IBO) injections and inhibition of LH neuronal elements by bilateral muscimol (MUSC) administration were also tested. It was found that pronounced hyposomnia follows electrolytic but not IBO lesions of the LH/MFB area. The effective LH damage might have been localized at every level of its antero-posterior axis, from the preoptic area up to the posterior hypothalamus, suggesting involvement of fiber system(s) rather than a localized group of neuronal pericaria. The most effective lesions transsected projections descending from the preoptic/anterior hypothalamic area, olfactory structures, ventral striatum and the central amygdaloid nucleus as well as fibers connecting LH with the brainstem reticular formation, many of them using GABA as a neurotransmitter. Bilateral MUSC injections caused a dose-dependent, bicuculline-reversible, increase in waking time, most pronounced at a dose of 50 ng, which ressembled the effect of the electrolytic lesion. These results indicate that LH hyposomnia is not attributable to the damage to the intrahypothalamic neurons and suggest the participation of GABA-ergic transmission in LH in waking-sleep regulation.

The effect of lateral hypothalamic lesions on spontaneous EEG pattern in rats.

Neocortical and hippocampal EEG was recorded in ten rats subjected to bilateral lesions of the lateral hypothalamus at different levels of its rostro-caudal axis. In nine rats the damage evoked a marked increase of waking time with a simultaneous reduction of the percentage of large amplitude irregular activity related to slow wave sleep in the first eight postlesion days. There was also a decrease in the amount of paradoxical sleep. Enhanced waking coexisted with behavioral somnolence. The most extensive hypothalamic lesions produced qualitative changes of EEG concerning mainly the frequency of hippocampal theta rhythm. Control lesions within the subthalamic region did not influence either qualitative or quantitative EEG pattern. It is concluded that limited lesions of the lateral hypothalamus did not destroy a sacient number of reticular activating fibers to disturb a cortical desynchronizing reaction. The increased amount of waking pattern may be due to serotonergic deafferentation of the neocortex. Dissociation of behavioral and EEG indices of the level of arousal imply the existence of separate neuronal systems for both aspects of activation.