, 2003 and Saper et al., 2005). This three-stage pathway from the SCN to the

subparaventricular zone and then to the dorsomedial nucleus appears necessary for conveying circadian information to the neurons that control wake-sleep state switching, yet it still allows some flexibility for altering the timing of sleep and wakefulness depending upon seasonal changes and the timing of food availability (Fuller et al., 2008, Gooley et al., 2006 and Mieda et al., 2006). In the absence of the dorsomedial nucleus, wake-sleep cycles become ultradian, with 7–8 sleep-wake cycles per day. In mice that are arrhythmic due to clock gene deletions, activity patterns likewise become ultradian (Bunger et al., 2000). However, there is a paucity of information concerning whether the wake-sleep cycles of individual animals become ultradian as well because the few learn more reports on sleep behavior in such mice provide only

graphs that summate across groups of animals, which obscures whether ultradian cycles (which are not synchronized across animals) were present (Laposky et al., 2005 and Wisor et al., 2002). Like lesions of the SCN in primates, lesions of the dorsomedial nucleus in rats, or deletions of certain clock genes (such as cryptochromes 1 and 2 or Bmal1), which cause loss of circadian cycling of the SCN in mice, reduce these the total amount of wakefulness ( Chou et al., 2003, Edgar et al., 1993, Laposky et al., 2005 and Wisor Carfilzomib ic50 et al., 2002). These observations suggest that the circadian system mainly promotes wakefulness during the active period, which is consistent with the main outputs of the dorsomedial nucleus being to inhibit the VLPO and excite

lateral hypothalamic neurons. Finally, animals often encounter conditions in their environment that require urgent alterations of specific physiological responses, including wake-sleep states. These would include stressful situations, such as confronting a predator or a hostile conspecific but also situations such as encountering a potential mate, seasonal changes, or the need for migration that may require an adjustment of wake-sleep behavior (Palchykova et al., 2003 and Rattenborg et al., 2004). These situations have been called allostatic loads by McEwen and colleagues ( McEwen, 2000), and they require additional circuitry for modifying wake-sleep cycles. One common stressor in the wild is a lack of food, and in small animals that can carry minimal energy reserves, the effects of food deprivation on sleep are dramatic. Food-deprived mice have marked increases in wakefulness and locomotor activity, probably reflecting a strong drive to forage for food.