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The Journal of Neuroscience, May 15, 2000, 20(10):3830-3842
Effect of Lesions of the Ventrolateral Preoptic Nucleus on NREM and REM Sleep
Jun Lu1, Mary Ann Greco2, Priyattam Shiromani2, and Clifford B. Saper1, 3 1 Department of Neurology and 3 Program in Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, and 2 Department of Psychiatry, Brockton Veterans Administration Hospital, Harvard Medical School, Boston, Massachusetts 02115
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.
Key words: preoptic area; hypothalamus; REM sleep; NREM sleep; thermoregulation; circadian rhythms
Copyright © 2000 Society for Neuroscience 0270-6474/00/20103830-13$05.00/0
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