These findings suggest that restricted feeding leads to entrainment of stomach clocks in ghrelin-expressing cells and food-entrained ghrelin signaling feeds back to the central nervous system to drive changes in FAA. Other neuronal systems including the hypocretin arousal Alectinib in vitro system (Akiyama et al., 2004; Mieda et al., 2004) and orexogenic melanocortin system (Sutton et al., 2008; Patton & Mistlberger, 2013) have been implicated in food entrainment, with disruptions to either system causing pronounced deficits in FAA. Most salient in daily life is the relationship between sleep and circadian rhythmicity. Associated with the timing of the rest–activity cycles are

rhythms in alertness/drowsiness, mood, and other behaviors. These cycles, and the processes that they impact, are an immense and fundamentally important topic, with much work in basic, clinical and pharmacological aspects (reviewed in Murray & Harvey, 2010; Harvey, 2011; Krystal et al., 2013; Saper & Sehgal, 2013). Although the details of sleep–circadian relationships are beyond the scope of this review, we highlight some major aspects. SB431542 in vitro The relationship between circadian clocks and sleep involves two interacting processes, and is captured

in the classical opponent process model of Borbely (1982). The homeostatic component of sleep involves a process whereby the sleep pressure (termed process S) increases the longer that an individual is awake. The neural locus regulating this homeostatic pressure is not well defined, and involves multiple brain regions and transmitters (see below). In contrast, the circadian system that regulates the timing of wakefulness and sleep has its well-characterized anatomical

locus in the SCN. The SCN has monosynaptic efferents to a number of nearby hypothalamic regions (reviewed in Morin, 2013), and these in turn relay information to a large number of brain regions, including those involved in regulating awake and sleep states. The neural circuits involved in sleep and arousal include the basal forebrain, brainstem, and hypothalamic components. The SCN has relatively Etofibrate few direct outputs to sleep–wake regulatory systems. Most of its output projects to nearby hypothalamic regions that relay signals to sleep and wake regulatory regions. The sleep circuits are comprised of numerous projections of neurons releasing different types of neurotransmitters and neuropeptides (reviewed in Saper et al., 2005) (Fig. 3). Briefly, arousal pathways include cholinergic neurons of the ascending arousal pathway, located in the pedunculopontine and laterodorsal tegmental nucleus, serotoninergic neurons in the dorsal raphe nucleus, noradrenergic neurons in the locus coeruleus, dopaminergic neurons in the median raphe nucleus, and histaminergic neurons in the tuberomammillary nucleus of the hypothalamus. Activity in these neurons promotes alertness and cortical arousal.