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Effect of Lesions of the Ventrolateral Preoptic Nucleus on NREM and REM Sleep

2000; Society for Neuroscience; Volume: 20; Issue: 10 Linguagem: Inglês

10.1523/jneurosci.20-10-03830.2000

1529-2401

Jun Lu, Mary Ann Greco, Priyattam J. Shiromani, Clifford B. Saper,

Sleep and related disorders

Neurons in the ventrolateral preoptic nucleus (VLPO) in rats show c-fos activation after sleep and provide GABAergic innervation of the major monoamine arousal systems, suggesting that they may be a necessary part of the brain circuitry that produces sleep. We examined the effects on sleep behavior in rats of cell-specific damage to the VLPO by microinjection of ibotenic acid. Severe lesions of the central cell cluster of the VLPO (∼80–90% cell loss bilaterally) caused a 60–70% decrease in delta power and a 50–60% decrease in nonrapid-eye-movement (NREM) sleep time ( p < 0.001). The number of remaining Fos-immunoreactive neurons in the VLPO cell cluster was linearly related to NREM sleep time ( r = 0.77; p < 0.001) and total electroencephalogram delta power ( r = 0.79; p < 0.001) but not to rapid-eye-movement (REM) sleep ( r = 0.35; p > 0.10). Lesions in the region containing scattered VLPO neurons medial or dorsal to the cell cluster caused smaller changes in NREM sleep time (24.5 or 15%, respectively) but were more closely associated with loss of REM sleep ( r = 0.74; p < 0.01). The insomnia caused by bilateral VLPO lesions persisted for at least 3 weeks. Lesions of the VLPO caused no change in mean body temperature or its circadian variation; after small lesions of the ventromedial preoptic nucleus, body temperature showed normal circadian variation but a wider temperature range, and sleep behavior was not affected. These experiments delineate distinct preoptic sites with primary effects on the regulation of NREM sleep, REM sleep, and body temperature.