Sleep is a temporary state of unconsciousness in which the brain is primarily responsive to
internal, rather than external stimuli.
Unlike other states of unconsciousness such as coma or general anesthesia, sleep is a natural,
cyclic process that is self-regulated and easily reversible to wakefulness.
Brain activity can be recorded in the form of electroencephalogram,
EEG, which measures electrical activities in the superficial layers of the cerebral cortex.
Different stages of consciousness correspond to different types of brain waves. A fully awake and
alert brain produces high-frequency low-voltage beta-waves. As consciousness decreases,
brain waves become progressively slower in frequency and higher in voltage.
There are 2 major phases of sleep: rapid eye movement, REM, sleep, and non-rapid eye
movement, non-REM, sleep. Non-REM sleep progresses in 3 stages: N1, N2 and N3
N1 is the transitional state between wakefulness and sleep. The EEG is dominated by alpha-waves.
The sleeper is easily awoken with light stimulation. N1 typically lasts a few minutes.
The next stage is N2, a deeper sleep state, where stronger stimuli are required to produce
awakening. Brain activity is slower and more irregular, with short bursts of “sleep
spindles” and “K-complexes.” It is believed that memory consolidation occurs during this stage.
N3 is deeper than N2. Slow delta-waves dominate.
Muscles relax, vital signs are at their lowest; and it is difficult to wake the sleeper.
N3 is typically followed by a transition to N2 before REM sleep occurs. As its name suggests,
REM sleep is characterized by rapid eye movements under the eyelids. It’s also known
as “paradoxical” sleep because the brain’s EEG is very much similar to that of the waking state. REM
sleep is when most dreams occur, as well as some autonomic reflexes. Vital signs are up, but there
is a total inhibition of skeletal muscles, which prevents sleepers from acting out their dreams.
This sequence of stages repeats itself 4 to 5 times in a typical night.
As the night progresses, the duration of N2 and REM sleep increases, while N3 decreases.
The amount and timing of sleep is regulated by 2 major factors:
homeostatic drive and circadian rhythm. Homeostatic drive is basically the body’s
need for sleep, or pressure to sleep. It is lowest after a good night sleep,
then starts to build up as we awaken. The need to sleep will continue to rise until sleep occurs.
Adenosine is thought to be a substance that accumulates with waking hours and drives
the pressure to sleep. Interestingly, caffeine appears to promote wakefulness
by acting as an antagonist of adenosine. The need to sleep increases with illness,
as well as cognitively stimulating or physically demanding activities.
Circadian rhythm is the body’s biological clock for the sleep-wake cycle. It determines
the timing of sleep. The master clock is located in the suprachiasmatic nucleus, the SCN, of the
hypothalamus. It receives light inputs from the retina and resets the clock everyday accordingly
to the day-night cycle. The SCN is most active during the day, and least active at night.
The sleep-promoting region is located in the ventrolateral preoptic nucleus, VLPO,
of the hypothalamus. The VLPO is inhibited by the SCN
and activated by adenosine. The VLPO uses GABA to inhibit
wake-promoting regions of the brain, which include multiple nuclei in the reticular formation
and posterior hypothalamus. Of these regions, it’s important to note the tuberomammillary
nucleus, TMN, and the hypocretin neurons. The TMN consists mainly of histaminergic neurons,
but it also produces GABA that inhibits VLPO in return. This mutual inhibition is the basis
of the “switch” between sleep and wake. The hypocretin neurons stimulate the TMN,
and are crucial for maintaining wakefulness. The loss of these neurons results in narcolepsy.
During the day, the SCN inhibits the VLPO and stimulates hypocretin neurons,
driving the switch towards the waking state. By the end of the day, when SCN activity is
lowest and pressure to sleep is highest, VLPO is activated, and sleep is “switched” on.
There is a similar switch between REM and non-REM sleep,
mediated by mutually inhibiting REM-on and REM-off neurons in the pons.