Brain structures and mechanisms involved in the generation of NREM sleep: focus on the preoptic hypothalamus

Dennis McGinty, Ronald Szymusiak
Sleep Medicine Reviews 2001, 5 (4): 323-342
Four lines of research have greatly increased our understanding of the hypothalamic preoptic area (POA) sleep-promoting system. First, sleep-active neurons within the POA have been identified using both electrophysiological recording and immediate early gene protein (c-Fos) staining methods. Segregated sleep-active neurons were found in ventrolateral and median POA (VLPO and MnPN). Additional sleep-active neurons may be intermixed with non-sleep specific neurons in other POA regions and the adjacent basal forebrain. Second, the putative sleep factors, adenosine and prostaglandin D2, were found to excite sleep-active neurons. Other sleep factors may also modulate these sleep-active populations. Third, many sleep-active neurons are warm-sensitive neurons (WSNs). WSNs are identified by excitatory responses to small increases in local POA temperature. The same local POA thermal stimuli strongly modulate sleep propensity and EEG delta activity within sleep. Interactions between sleep regulation and thermoregulation are consistent with studies of circadian sleep propensity, prolonged sleep deprivation in rats, and species differences in sleep amounts. Fourth, sleep-active neurons were found to co-localize the inhibitory neurotransmitter, gamma-aminobutyric acid and to have projections to arousal-related neuronal subgroups in the posterior hypothalamus and midbrain. Sleep-active and arousal-related neurons exhibit reciprocal changes in discharge across the wake-NREM-REM cycle, and activation of WSNs suppresses the neuronal activity of some arousal-related neuronal groups. These studies establish mechanisms by which POA hypnogenic neurons can inhibit EEG and behavioral arousal. In addition, there is evidence that arousal-related neurotransmitters inhibit VLPO sleep-active neurons. Mutually inhibitory interactions between sleep-promoting and the arousal system provide a substrate for a <sleep-wake switch>. 2001 Harcourt Publishers Ltd

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