Mechanisms of Sleep

Question 1

Write an introduction to sleep

Answer 1

• Sleep accounts for a considerable part of daily activity, greatly vary in duration and quality between individuals.
• Human sleep deprivation studies (Horne, 1978) demonstrate its importance in mental performance and wellbeing, whilst animals show weakness, incoordination and eventual death following prolonged deprivation (Rechtshaffen et al., 1989).
• Contrary to popular belief, sleep is not a loss of consciousness following a strenuous day.
• It is actually a period of intense activity existing along a continuum of consciousness (Garrett, 2015), requiring activity inhibition of arousal systems.
• This essay will discuss the various systems involved in sleep and the mechanisms of inhibition upon the arousal systems.

Question 2

What is the role of the circadian rhythm in regards to sleep?

Answer 2

• Despite our incomplete knowledge of sleep’s role, it continues to every ~24 hour interval.
• This cycle is known as the circadian rhythm. It determines many bodily functions including hormone release, nervous system activity, and temperature control.
• Every organism possesses its own internal body block, known as the free-running cycle, which is entrained/synchronised with external cues to follow a day/night cycle (Carlson, 2010).
• The circadian rhythm is maintained by pacemake cells of the suprachiasmatic nucleus (SCN) (Garrett, 2015), which is highly metabolically active during the day.
• Animal models with SCN lesions lose their free-running cycle and display erratic sleeping patterns (Carlson, 2010), implicating an important role of the SCN in sleep.

Question 3

Discuss the sleep-promoting system in the brain

Answer 3

• Central to sleep are the existence of sleep-promoting and arousal systems in tandem.
• The former exists with the ventrolateral preoptic area (vlPOA), that is damaged in human and animal models of insomnia (Carlson, 2010).
• Preoptic neurones project form the vlPOA to various nuclei of the arousal systems.
• These neurones exert GABA-mediated inhibition to induce drowsiness (Saper, Scammell & Lu, 2005).

Question 4

What is the role of adenosine in sleep?

Answer 4

• Research implicates adenosine as a sleep-promoting substance (Carlson, 2010).
• Prolonged wakefulness requires continuous energy conversion of glycogen by astrocytes.
• Depletion of these glycogen stores results in accumulation of adenosine and stimulation of the vlPOA (Kong et al., 2002).
• Slow-wave sleep has been found to replenish astrocyte glycogen (Wigren et al., 2007) and reduce adenosine levels (Porkka-Heiskanen et al., 2010).

Question 5

Provide an overview of the arousal systems in the brain

Answer 5

• Wakefulness involves activation of most neurones in the brain to carryout various tasks thoughout the day (Carlson, 2010).
• This involves several neurotransmitter systems responsible for arousal, spread across multiple areas of the brain.
• Acetylcholine, noradrenaline, serotonin, and histamine, all play a direct role in arousal (Carlson, 2010).

Question 6

What is the flip-flop mechanism within sleep?

Answer 6

• These two opposing systems are said to exist in flip-flop (Carlson, 2010).
• This is characterised by mutual inhibition, mediated by GABA, where only one system is active at a time with no intermediate states.

Question 7

Discuss the role of the orexin system in sleep

Answer 7

• The orexin system mediated which of the sleep-promoting and arousal systems is currently active.
• It projects excitatory neurones towards the arousal system, promoting wakefulness and inhibiting sleep (Saper et al., 2001).
• Inputs into the orexin system include excitation from SCN activity (Saper, Scammell & Lu, 2005) and hunger signales, and inhibition from satiety signals (Carlson, 2010).
• Additionally, the vlPOA inhibits the orexin system (Carlson, 2010), meaning adenosine accumlation during prolonged waking can inhibit the orexin system and remove its excitatory effect on arousal systems.
• This is supported by findings that orexin antagonists promote sleep in both human and animal models (Brisbare-Roch et al., 2007).

Question 8

What is the melatonin? Describe its role in sleep

Answer 8

• Melatonin is an endogenous hormone, also licenced as insomnia treatment (NICE, 2019), that in diurnal species reduced alterness and prepares the body for sleep (Society of Endocrinology, 2018), by attenuating the arousal signaled emitted by the SCN (Liu et al., 1997).
• The pineal gland secretes melatonin when light levels decrease with night-time (National Sleep Foundation, n.d.).
• Ultimately the control of melatonin is determined by inhibtion from the SCN in the day.
• Additionally, bright light can inhibit melatonin secretion, reducings its release by 90 minutes each night (Gooley et al., 2010).

Question 9

Write a conclusion

Answer 9

• In conclusion, sleep is not a loss of consciouness following a strenuous day.
• Its initiation involves complex biological mechanisms including the accumulation of adenosin, in response to proloned wakefulness, and the secretion of melatonin during night time.
• Individuals seek dark and quiet areas that typicall signify night-time.
• A flip-flop mechanism exists between sleep-promoting systems in the vlPOA and arousal systems across multiple brain areas.
• This is mediated by the orexin system, which stimulats arousal systems.
• Adenosine stimulates the vlPOA to both directly promote sleep, and indirectly through inhibition of orexin.
• Melatonin in humans indirectly promotes sleep by attenuating SCN influence on arousal systems.
• Ultimately, the initiation of sleep is via inhibtion of brain activity of the arousal systems active during waking.