The Sleep-wake cycle is a diurnal rhythm the human body oscillates in between awake and sleeping states, the mechanics of which span several fields of science including psychophysiology, endopharmacology, metabolomics, and psychology. In this cycle a person will optimally spend 7 hours in the sleep state which is similar on the surface to unconsciousness (although the phenomenon of lucid dreaming is contradictory to the term unconsciousness). The sleep state is often preformed at night as this is the evolutionary norm for humans, as evidenced by the fact that the hormone melatonin is released during darkness and contributes to the desire to sleep. Although melatonin in this instance serves as a regulatory mechanism for making sure humans sleep once a day during night, it is not the causative factor as humans are able to sleep even during daylight if they are sleepy enough. Though it should be noted that this can lead to circadian rhythm sleep disorders.
The biological process outlined here is cyclic and although it is outlined in a linear form it is better understood in a way that the end leads to the beginning to start over again. This cycle can be broken down into three main phases which are outlined below.
- Lack of Adenosine activating the (A(2A)R) receptor is sufficient to have decreased GABA release in the tuberomammillary nucleus enough to have enabled histamine to wake one up and cause vigilance.
- Exposure to blue light frequencies mainly between 460 and 480nm trigger melanopsin cells in the eyes to send a signal to the suprachiasmatic nucleus which sends GABA to the pineal gland, inhibiting it from releasing melatonin thereby causing levels to decline.
- The food eaten before sleep has been digested and the stomach is empty which releases ghrelin, this causes hunger by inducing the release of the hormone orexin and thereby pushing one to eat.
- ATP from the food is metabolized into adenosine which begins to accumulate around the adenosine receptors.
- The decreasing of the light levels which were activating melanopsin cells begins to shut off the signal to the suprachiasmatic nucleus, stopping GABA from being sent to the pineal gland allowing melatonin to be released.
- In the presence of insulin melatonin causes upregulation of leptin, thereby inhibiting the hunger hormone orexin allowing one to fast while they sleep. (If one has been fasting before sleep insulin levels will be low causing melatonin to downregulate leptin instead of upregulating it, thus encouraging one to eat before they sleep)
- High levels of adenosine activating the adenosine receptor A1 inhibit cholinergic neurons in the basal forebrain thus gradually causing cognitive decline.
- In addition activation of adenosine receptor (A(2A)R) causes the release of GABA in the tuberomammillary nucleus to inhibit histamine, thus gradually inducing sleepiness.
- Food is Digested throughout the night, sustaining insulin levels which in combination with melatonin cause the upregulation of leptin. This inhibits orexin allowing one to sleep without being distracted by hunger.
- The falling levels of adenosine enable the cholinergic neurons in the basal forebrain to become uninhibited to activation.
- As adenosine is metabolized and it's levels decrease it no longer leads to the GABAergic inhibition of histamine, allowing vigilance to increase.
- As these elements of wakefulness begin to return REM cycles and brief awakenings occur with increasing density, eventually resulting in a full awakening.
- Kripke, D. F., Garfinkel, L., Wingard, D. L., Klauber, M. R., Marler, M. R. (1 February 2002). "Mortality Associated With Sleep Duration and Insomnia". Archives of General Psychiatry. 59 (2): 131. doi:10.1001/archpsyc.59.2.131. ISSN 0003-990X.
- Zhdanova, I. V., Wurtman, R. J., Lynch, H. J., Ives, J. R., Dollins, A. B., Morabito, C., Matheson, J. K., Schomer, D. L. (May 1995). "Sleep-inducing effects of low doses of melatonin ingested in the evening". Clinical Pharmacology and Therapeutics. 57 (5): 552–558. doi:10.1016/0009-9236(95)90040-3. ISSN 0009-9236.
- Hong, Z.-Y., Huang, Z.-L., Qu, W.-M., Eguchi, N., Urade, Y., Hayaishi, O. (March 2005). "An adenosine A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats". Journal of Neurochemistry. 92 (6): 1542–1549. doi:10.1111/j.1471-4159.2004.02991.x. ISSN 0022-3042.
- Thakkar, M. M. (February 2011). "HISTAMINE IN THE REGULATION OF WAKEFULNESS". Sleep medicine reviews. 15 (1): 65–74. doi:10.1016/j.smrv.2010.06.004. ISSN 1087-0792.
- Brainard, G. C., Hanifin, J. P., Greeson, J. M., Byrne, B., Glickman, G., Gerner, E., Rollag, M. D. (15 August 2001). "Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor". The Journal of Neuroscience: The Official Journal of the Society for Neuroscience. 21 (16): 6405–6412. ISSN 1529-2401.
- Colwell, C. S. (October 2011). "Linking neural activity and molecular oscillations in the SCN". Nature Reviews Neuroscience. 12 (10): 553–569. doi:10.1038/nrn3086. ISSN 1471-0048.
- Kalsbeek, A., Cutrera, R. A., Heerikhuize, J. J. van, Vliet, J. van der, Buijs, R. M. (June 1999). "GABA release from suprachiasmatic nucleus terminals is necessary for the light-induced inhibition of nocturnal melatonin release in the rat". Neuroscience. 91 (2): 453–461. doi:10.1016/S0306-4522(98)00635-6. ISSN 0306-4522.
- GHRL ghrelin and obestatin prepropeptide [Homo sapiens (human)] - Gene - NCBI
- MOLECULES THAT BUILD UP AND MAKE YOU SLEEP
- Alonso-Vale, M. I. C., Andreotti, S., Peres, S. B., Anhê, G. F., Neves Borges-Silva, C. das, Neto, J. C., Lima, F. B. (April 2005). "Melatonin enhances leptin expression by rat adipocytes in the presence of insulin". American Journal of Physiology. Endocrinology and Metabolism. 288 (4): E805–812. doi:10.1152/ajpendo.00478.2004. ISSN 0193-1849.
- Hawryluk, J. M., Ferrari, L. L., Keating, S. A., Arrigoni, E. (15 May 2012). "Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons". Journal of Neurophysiology. 107 (10): 2769–2781. doi:10.1152/jn.00528.2011. ISSN 0022-3077.
- Hasselmo, M. E. (December 2006). "The Role of Acetylcholine in Learning and Memory". Current opinion in neurobiology. 16 (6): 710–715. doi:10.1016/j.conb.2006.09.002. ISSN 0959-4388.
- Huang, Z.-L., Urade, Y., Hayaishi, O. (2011). "The role of adenosine in the regulation of sleep". Current Topics in Medicinal Chemistry. 11 (8): 1047–1057. doi:10.2174/156802611795347654. ISSN 1873-4294.
- https://en.wikipedia.org/wiki/Rapid_eye_movement_sleep#/media/File:Sleep_Hypnogram.svg | Hypnogram of sleep between midnight and 6.30 am