Specific brainstem regions regulate the transitioning of the five sleep stages. For example, NREM occurs when the noradrenergic LC and serotonergic dorsal raphe (DR) suppress the cholinergic pedunculopontine tegmentum (PPT) and lateral dorsal tegmentum nuclei (LDT) neurons. In contrast, entry into REM sleep is associated with a decrease in noradrenergic LC and serotonergic DR activity that permits enhanced activity of the cholinergic PPT and LDT (Pace-Schott & Hobson, 2002). Perturbations in neurotransmitter signaling between these nuclei can interfere with REM/NREM oscillations, leading to impaired sleep.
Neurocircuitry utilizes maps depicting interactions between specific neuronal centers in the brain and periphery in order to relate urinary neurotransmitter output to central nervous functions. Activity in specific brainstem nuclei is associated with the release of neurotransmitters in the periphery (Lechin et al., 2004; Vgontzas et al., 1998). Analysis of night-time urinary neurotransmitters can be helpful in determining perturbations in neurocircuitry, and in guiding and monitoring therapeutic interventions. For instance, overactivity of certain wake centers in the brain can trigger sympathetic nerves to release norepinephrine in the periphery, with elevated urinary norepinephrine levels correlated with an overactive sympathetic nervous system (Vgontzas et al., 1998). Therapeutic strategies that successfully target CNS nuclei to regulate sympathetic outflow will result in a decrease in urinary norepinephrine output.
In another example, exercise-induced increases in epinephrine correlate with a delay in REM sleep onset (Netzer et al., 2001), and total REM sleep is significantly lower following exercise (Netzer et al., 2001). Correlating with this, exercise has been shown to stimulate an increase in urinary epinephrine (Netzer et al., 2001). Therefore, urinary catecholamines appear to be biomarkers of altered REM sleep.