This is an inhibitory neurotransmitter found in the spinal cord and inhibits motoneurons and thus is involved in the atonia associated with REM sleep.
Serotonin (5HT)
As previously discussed, the primary role of 5HT is in wakefulness, as well as the control of many different functions. There are many different receptors for 5HT and one specific group is involved in sleep. In this instance, 5HT is involved in NREM sleep; however, it is minimally present during REM sleep [31]. 5HT is derived from L‐tryptophan, an amino acid.
The Role of Melatonin
This is a hormone that is released by the pineal gland in the brain and its major impact is on the CR. Melatonin does not directly impact sleep like other neurotransmitters. The role of melatonin is to prepare areas of the brain for the action of neurotransmitters that promote sleep [41]. As such the release of melatonin is related to light. Light that penetrates the eye has an impact on the release of melatonin in a negative fashion. In the presence of light, the release of melatonin is turned off. As darkness approaches the absence of light, penetrating the eye is the stimulus to release melatonin thus promoting sleep.
The pathway that impacts the release of melatonin is not a direct one. The absence of light triggers neural activity that proceeds from the suprachiasmatic nucleus (SCN) in the brain stem to the hypothalamus. The signal proceeds to the superior cervical nucleus of the spinal column and then to the pineal gland (Figure 2.5).
Flip‐Flop Switch
The neurotransmitters involved in the sleep–wake cycle interact such that they have an effect on one other, referred to as the flip‐flop switch. This is viewed as a balance between the wake promoting and sleep promoting neurotransmitters. In this model, there is a trigger that causes a switch in states between sleep and wakefulness to occur [42].
The Circadian Rhythm
Our CR or cycle is directly related to the light‐dark cycle and in turn to our sleep–wake cycle. It is derived from the Latin circa (around) and diēm (day). The human CR is slightly more than 24 hours in length and is controlled by the SCN. Adjustment to the CR, termed entrainment, is facilitated by external cues called zeitgebers (time givers), such as light, temperature, and social interaction. There are two other rhythms besides CR:
1 Infradian rhythms are greater than 24 hours, such as menstruation and seasonal depression.
2 Ultradian rhythms are shorter than CR such as heart rate, nostril dilation, and appetite.
The Gut Microbiome
The role of the gut microbiome (GM) on sleep as well as other physiologic activities has been a developing area of interest from the standpoint of the impact it may have in humans. It has been shown that alterations in the GM may impact sleep, blood pressure, our circadian rhythm, and even cognition [43, 44]. In the future, our sleep and the management of sleep disorders may be impacted by the interaction between the gut and brain [45], often referred to as the gut‐brain axis.
Figure 2.5 Release of melatonin.
Conclusion
Human sleep is a complex interrelationship between a wide variety of neurotransmitters and how they impact the brain and one another. Having a basic understanding of neuroanatomy as well as neurobiology is also important as it helps to understand brain function in sleep and wakefulness. Our sleep is no longer viewed as an alternate state of consciousness but rather a separate state of being with unique properties that are designed to facilitate improved health, mood, memory, and well‐being. Over time a better understanding of the neurotransmitters involved in sleep will no doubt occur, resulting in a better understanding of sleep. Ultimately, sleep is controlled by the brain and is for the brain.
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