Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep.
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 ( approximately 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.
Lu
J
J
Department of Neurology and Program in Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Greco
M A
MA
Shiromani
P
P
Saper
C B
CB
D000818:Animals; D015415:Biomarkers; D001831:Body Temperature / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D003700:Delta Rhythm; D003714:Denervation; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D011301:Preoptic Area / Q000166:cytology / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms
D015415:Biomarkers; D018690:Excitatory Amino Acid Agonists; D016760:Proto-Oncogene Proteins c-fos; D007051:Ibotenic Acid