With the development of accurate and sensitive assays for measuring urinary and salivary biomarkers, researchers have made great strides toward understanding the brain circuitry that controls sleep-wake states (Burgess & Fogg, 2008; Lechin et al., 2004; Westermann et al., 2002).
During wakefulness, the brain is kept active and alert by the actions of acetylcholine, norepinephrine, serotonin, dopamine, and histamine (Pal & Mallick, 2007). A region in the brain called the suprachiasmatic nucleus (SCN) entrains the body’s response to light (Turek et al., 2001), and is referred to as the master internal circadian clock (Castillo et al., 2004). Light activating photoreceptors in the eye promotes glutamatergic projections to the SCN. The SCN triggers several pathways that activate wake centers in the brain, such as the locus coeruleus (LC) and the tuberomammillary nucleus (TMN). The LC primarily releases norepinephrine, a neurotransmitter that contributes to elevated energy, mood, and vigilance (Comings et al., 2000). The TMN releases histamine, a neurotransmitter that promotes wakefulness and arousal (Wada et al., 1991). Excess release of norepinephrine and histamine results in a state of wakefulness (Lewy, 2002).
In the absence of light, activity in the SCN is inhibited, while brain regions that are responsible for sleep such as the ventral lateral preoptic (VLPO) area and pineal gland are activated. The VLPO sends inhibitory GABAergic projections to wake-promoting centers in the brain, and in doing so reinforces sleep onset (Pace-Schott & Hobson, 2002). An increase in pineal gland activity results in the release of melatonin, a hormone that further dampens the activity of the SCN (Redlin, 2001). Therefore, excess release of GABA and melatonin results in a sleep-state (Lewy, 2002).
There are four stages of sleep defined by electroencephalogram (EEG) readings, include three stages characterized as non-rapid eye movement sleep (NREM), and another stage classified as rapid eye movement (REM) sleep (Dotto, 1996). REM sleep encompasses dreaming, increases in respiration, heart rate, and body temperature. During a typical night’s sleep, a person completes five cycles of these sleep stages. The REM periods become incrementally longer with each cycle, ranging from 10 minutes to about an hour (Figure 2) (Dotto, 1996).