Selective Activation of the Extended Ventrolateral Preoptic Nucleus during Rapid Eye Movement Sleep

Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 07/2002; 22(11):4568-76.
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We found previously that damage to a cluster of sleep-active neurons (Fos-positive during sleep) in the ventrolateral preoptic nucleus (VLPO) decreases non-rapid eye movement (NREM) sleep in rats, whereas injury to the sleep-active cells extending dorsally and medially from the VLPO cluster (the extended VLPO) diminishes REM sleep. These results led us to examine whether neurons in the extended VLPO are activated during REM sleep and the connectivity of these neurons with pontine sites implicated in producing REM sleep: the laterodorsal tegmental nucleus (LDT), dorsal raphe nucleus (DRN), and locus ceruleus (LC). After periods of dark exposure that triggered enrichment of REM sleep, the number of Fos-positive cells in the extended VLPO was highly correlated with REM but not NREM sleep. In contrast, the number of Fos-positive cells in the VLPO cluster was correlated with NREM but not REM sleep. Sixty percent of sleep-active cells in the extended VLPO and 90% of sleep-active cells in the VLPO cluster in dark-treated animals contained galanin mRNA. Retrograde tracing from the LDT, DRN, and LC demonstrated more labeled cells in the extended VLPO than the VLPO cluster, and 50% of these in the extended VLPO were sleep-active. Anterograde tracing showed that projections from the extended VLPO and VLPO cluster targeted the cell bodies and dendrites of DRN serotoninergic neurons and LC noradrenergic neurons but were not apposed to cholinergic neurons in the LDT. The connections and physiological activity of the extended VLPO suggest a specialized role in the regulation of REM sleep.

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    • ") , and then incubated in the primary antiserum for 1 day at room temperature . For c - Fos , we used a rabbit polyclonal antiserum ( AB5 ; 1 : 50 , 000 ; Oncogene Sciences , Cambridge , MA , USA ) against residues 4 – 17 from human c - Fos . This antiserum stains only the nuclei of neurons based on recent activity patterns ( Gaus et al . , 2002 ; Lu et al . , 2002 ) . For Cre , we used a rabbit polyclonal antiserum ( Novagen , lot #D00132036 , catalog #69050 , 1 : 10 , 000 ) . Sections were then washed in PBS and incubated in biotinylated secondary antiserum ( 1 : 1000 in PBS ) for 1 h , washed in PBS , and incubated in avidin - biotin - horseradish peroxidase conjugate ( Vector Laboratories ) fo"
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