A key property of VLPO neurons is that they receive reciprocal inputs from many regions implicated in arousal, including the TMN, dorsal raphe nucleus and adjacent ventral periaqueductal gray matter (vlPAG), parabrachial nucleus, and LC (Chou et al., 2002 and Lu et al., 2006a). Slice recordings of identified VLPO neurons show that they are inhibited by acetylcholine, norepinephrine,

dopamine, and serotonin (Gallopin et al., 2000 and Gallopin et al., 2004). While VLPO cells are not inhibited by histamine, the TMN neurons also contain the mu-opioid peptide endomorphin, which inhibits VLPO neurons (Greco et al., 2008). MnPO neurons receive only sparse inputs from the LC and periaqueductal gray matter and little if any from the dorsal or median BMS-777607 molecular weight raphe nuclei or from the TMN (Saper and Levisohn, 1983). The effects of these inputs on the MnPO sleep-active neurons remain unknown. Because even rats with very large

VLPO lesions still sleep about 50% as much as normal animals, it is likely that the sleep-promoting system in the brain is distributed with components in addition to the VLPO that may contribute to the inhibition of the arousal systems during sleep. These may include other sleep-active neurons in the MnPO and basal forebrain (Modirrousta et al., 2004 and Takahashi et al., 2009), but evidence that these cells promote sleep is lacking. GPCR Compound Library mouse Recent studies on lesions of the striatum and globus pallidus have reported substantial increases in wakefulness and sleep fragmentation (Qiu et al., 2010). The descending projections from both the nucleus accumbens and globus pallidus are largely GABAergic and include the basal forebrain and lateral hypothalamus (Baldo et al., 2004, Kim et al., 1976 and Swanson and Cwan, 1975). In addition, a population of cortical neurons has been described that express

cFos during sleep and are immunoreactive for both nitric oxide and neuropeptide Y (Gerashchenko et al., 2008). However, their role in producing sleep states, or in state switching, remains to be studied. Thus, although FGD2 it is likely that other sleep-promoting neurons participate in the induction and maintenance of sleep, the VLPO neurons appear to play a particularly important role in this process, as VLPO lesions can substantially reduce sleep for months (Lu et al., 2000). Therefore, in our model for behavioral state switching, we will focus on the interactions of the VLPO with wake-promoting systems. After the discovery of REM sleep in the 1950s, its regulation became a major focus of research. Much work has indicated that neurons in the pons play an essential role as REM sleep is disrupted by transections of the pons or large excitotoxic lesions of this region (Jouvet, 1962 and Webster and Jones, 1988). In addition, just prior to and during REM sleep, high-voltage EEG waves occur in the pons, lateral geniculate, and occipital cortex (hence PGO waves) in cats.