Neurophysiology and Neurochemistry of Sleep

Neurophysiology and Neurochemistry of Sleep

The non-REM–REM sleep cycle is regulated within the brain stem. Consistent with the concept that the brain stem regulates REM sleep, an Israeli soldier ceased having REM sleep after suf-fering a shrapnel wound to the brain stem (Lavie et al., 1984). Some antidepressant medications, notably monoamine oxidase inhibitors (MAOIs), completely eliminate REM sleep when they are taken at high clinical doses for more than 2 weeks. No spe-cific deleterious effects have been attributed to the loss of REM sleep in these patients. These observations underscore the mys-tery about the fundamental functions of REM sleep in particular and sleep in general.

No specific “sleep neurotransmitter” has been identified neuromodulators, neuropeptides, immune modulators) have been implicated. Adenosine is a potential sleep promoting neu-rotransmitter; its concentration in basal forebrain increases with prolonged wakefulness. Caffeine probably promotes alertness by blocking the adenosine A₁-receptor. Of particu-lar importance to psychiatry, acetylcholine, released from neurons originating in the dorsal tegmentum, induces REM sleep and cortical activation. Serotonin and norepinephrine, on the other hand, inhibit REM sleep, possibly by inhibition of cholinergic neurons responsible for REM sleep. These physiological mechanisms may be involved in both depres-sion and the sleep disturbances associated with depression and other neuropsychiatric disorders, such as short REM latency (see later). For example, depression may be associated with a functional serotonin deficiency. The suppression of REM sleep during treatment with antidepressants may reflect either enhanced serotoninergic or noradrenergic neurotransmission or anticholinergic effects.

In addition, considerable current research suggests that sleep and immunological processes are intimately related. Sev-eral neuroimmunomodulators, such as specific interleukins or tumor necrosis factor, may promote sleep and sleep deprivation may alter immune function, for example, reducing activity of natural killer cells.