“Sleep that knits up the ravelled sleeve of care

The death of each day’s life, sore labour’s bath

Balm of hurt minds, great nature’s second course,

Chief nourisher in life’s feast”

– William Shakespeare


Despite common belief that sleep is a period of neural and physiological inactivity, some parts of the brain are actually more active during rest than during times of wakefulness. Our slumber — although accompanied by impressions of tranquility — is a very lively component of our diurnal routine.

Sleep is divided into five stages: 1,2,3,4, and REM (Rapid Eye Movement). We spend about half of our time sleeping in stage 2 and 20% in REM sleep. Stages 1-4 increase in the depth of sleep, as more delta waves are released, and it becomes difficult to wake somebody in stages 3 or 4. However, REM sleep, sometimes referred to as paradoxical sleep, is the most fascinating part of the sleep cycle. Lasting 70-90 minutes, our eyes move rapidly and randomly, our blood pressure and heart rate increases, we become immobile, and envision vivid and illogical tales that appear fragmented but seem entirely real: we dream.

Although we have not identified the reason why we sleep, we have a few conjectures. Some suggest we sleep in order to process and consolidate thoughts from the day. Memory consolidation is enhanced by proper sleep, as increased neuroplasticity and an enhanced neural network creates connections in our brains. During Slow Wave Sleep (stages 3 and 4), ideas and memories temporarily stored in the hippocampus gradually are transferred to the cortex for long-term storage. Moreover, some believe that sleep bolsters brain function. Sleep promotes concentration, attention, decision making, and health while inhibiting impulsivity, anger, and stress. Finally, others believe sleep is a time for our bodies to “restore” itself through actions such as repairing DNA and enhancing immune and respiratory system efficiency.

The release of specific neurotransmitters in the brain operate in tandem with the “homeopathic drive to sleep,” our innate desire to sleep, and our circadian rhythm, a biochemical mechanism located in the hypothalamus of our brain. The hypothalamus acts as the “pacemaker” and regulates our circadian rhythm, an essentially innate behavioral, mental, and physical diurnal routine many organisms follow that is primarily driven by changes in light. Thus, our body runs on this esoteric circadian clock, governing when we must remain alert and vigilant or at what times we can slip into the unconscious state of sleep.

The mechanisms that control wakefulness are not concentrated in any particular part of the brain, but rather resides in the brainstem, hypothalamus, and basal forebrain. In the hypothalamus, the ventrolateral preoptic nucleus (VLPO) promotes feelings of tiredness by inhibiting neurons in the brainstem that promote wakefulness. In addition, the anterior hypothalamus releases GABA neurotransmitters to further inhibit wakefulness, leading to the generation of Slow-Wave Sleep.

Similarly, as part of the process of “mutual inhibition,” other parts of the brain stimulate the cerebral cortex — the neural region that maintains activity, learning, and consciousness — and deactivate the VLPO and its functionality during the day. A host of neurochemicals in the brain underpin our ability to stay awake throughout the day. Histamine, a molecule popularly associated with immune responses to allergies, is the key wakefulness-promoting neurotransmitter, exhibiting high concentrations throughout the day and showing small measures during REM (Rapid Eye Movement) and non-REM sleep. Also, acetylcholine, a chemical associated with motor function and muscle contraction, is important in the reticular activating system, the network of neurons in the brainstem that promotes wakefulness, and stimulates activity in the forebrain and cerebral cortex.

To flip the switch, multiple processes must occur. First, orexin, a neurotransmitter in the hypothalamus, is found in high concentrations during the day. Throughout the day, however, it gradually lessens, thus promoting sleep. Moreover, the thalamus, or the “gatekeeper” that motor and sensory signals pass through to reach the cerebral cortex, blocks signals for wakefulness. The thalamus sends slow brain waves typical of deep sleep to the thalamus, allowing the region of the brain to “relax” from the normally rapid, cortical firing. Also, small cell-signaling protein molecules called cytokines also send messages for sleep. Although these molecules are normally known for their roles in immune responses, they play a dual role in inducing reactions that stimulate drowsiness. This is why some diseases such as the flu produce lethargy and fatigue.

In addition, serotonin is naturally released by the body throughout the day. Serotonin is then converted into melatonin, known as the key sleep hormone, in the pineal gland under regulation by the body’s internal clock. Melatonin plays a huge role in causing sleep, and is popular as an OTC supplement. Melatonin production is increased at night, and helps cause tiredness and lower body temperatures. Melatonin actually does not actively cause sleep, but rather it inhibits the circadian alerting system in our brain (a mechanism which interferes with the homeostatic drive to sleep and creates the circadian drive for arousal by sending an alerting pulse throughout the body).

As we become rested and the day begins, melatonin diminishes to negligible amounts and cortisol, a stress hormone, is released to prepare for the stress of the upcoming day.


– Josh Metzger ’17