“Rise and shine!” Or, better said, “shine and rise!” The sun provides a central cue for waking hours because the light it emits serves as a regular signal that enforces the daily cycles of the human brain. Likewise, the absence of light serves as a signal for sleeping and rest for diurnal creatures. Without light perception, how can these cues be followed, and how can the body’s rhythms, including sleep, be regulated?
Naptime Networks: The Mechanisms of the Circadian Rhythm and Sleep
Sleep is regulated by the circadian rhythm, a set of physiological processes that roughly follow a 24-hour cycle. This rhythm is vital for several mechanisms in the body, including core body temperature, hormone release, and the sleep-wake cycle. Without external cues, a normal human’s circadian rhythm will run slightly longer than a solar day, at around 24.2 hours, only setting into a 24-hour daily cycle through entrainment .
Entrainment, the process of aligning the body’s internal clock to the solar day, uses light to determine when the day begins and ends. It proceeds as follows: light is sensed by specific receptors in the eye, sending signals to an area of the brain called the suprachiasmatic nucleus of the hypothalamus. Hypothalamic action suppresses melatonin, the hormone that signals when light is not present—indicating ‘nighttime’ when it courses through the body.
The first part of entrainment comes in the reception of light in the eyes. Light is sensed through photoreceptors in the retina, a cell layer in the back of the eye . Photoreception (the sensation of light) occurs when light-sensitive pigments undergo a shape change after light stimulation. This shape change sends signals to retinal ganglion cells, special cells that relay the signal to the brain, where the signals are processed and perceived as light. Sight is enabled by the signals from these retinal ganglion cells, which receive signals from photoreceptive ‘rods’ and ‘cones.’ The cells that entrain the circadian rhythm are similar yet distinct from these rod and cone cells . These cells are intrinsically photosensitive retinal ganglion cells (ipRGCs), and contain a photopigment called melanopsin, which responds to blue light frequencies. Unlike rods and cones, ipRGCs have a slow, sustained response to light, which increases with continued stimulation .
ipRGC’s unique features play a vital role in their function, as they signal to non-image-forming visual functions that benefit from having more time to integrate the information . After light stimulation, the ipRGCs signal through the retinohypothalamic tract (RHT) to the suprachiasmatic nucleus (SCN) . The SCN uses these signals to synchronize the circadian rhythm by controlling melatonin release. This hormone then adjusts the circadian rhythm accordingly .
Melatonin essentially serves as a ‘darkness hormone,’ as light suppresses its secretion . Melatonin courses through the body and is received by a variety of receptors, most of which are within the SCN itself. Two known melatonin receptors, MT1 and MT2, receive and relay information depending on the timing of melatonin release. The MT2 receptors appear to be responsible for the shifting and re-aligning of the circadian rhythm with the solar day, whereas the MT1 receptor promotes drowsiness and sleep. Throughout the day, melatonin will follow a regular cycle in the body, appearing prior to sleep, peaking between two and four in the morning, and dropping off near the morning [5,6].
For easier visualization, imagine melatonin as a night-shift messenger, and the SCN as the messenger headquarters. In the dark, melatonin walks around the body, going up to each receptor and adjusting their clocks. When light enters the eye, it flips a switch that sends a telegram to the SCN. Seeing the telegram, the SCN announces the end of melatonin’s shift, so no more melatonin leaves HQ to set receptor clocks. The arrival and departure of melatonin thus signal the beginning and end of the day, as controlled by the SCN ‘headquarters.’
Through the melatonin pathway, light entrains the circadian rhythm, which sets and regulates the biological sleep/wake cycle . Suppression of melatonin earlier in the day ‘advances’ the circadian rhythm, promoting earlier wakefulness. Likewise, light exposure later in the day, like the prolonged solar day in the summer, will extend the biological day. In this way, the body optimizes when certain processes occur and can prepare for resting hours ahead of time as well as prime the body for waking by raising internal body temperature [7,8] .
Going to Bed Without a Night-Light: Effects of Blindness on the Circadian Rhythm
Without entrainment, even light-perceiving individuals may develop “free-running” cycles that deviate from the 24-hour cycle. Light-perceiving individuals include all people who can detect light, including the legally blind who may have useless but present vision. Concerning circadian entrainment, any individual with functional ipRGCs are ‘light perceiving,’ while those without ipRGC signaling are ‘non-light perceiving.’ In non-light perceiving people, the circadian rhythm may become very out of sync with the regular pattern of their social and work lives, creating problems like circadian rhythm sleep disorders. These include delayed sleep phase syndrome (DSPS) and advanced sleep phase syndrome (ASDS). DSPS and ASDS both feature regular 24-hour cycles that are either set later in the day (delayed) or earlier in the day (advanced). For example, an individual affected by ASDS may wake up very early and become sleepy in the afternoon. More common is the “free-running” cycle, in which the circadian cycle runs longer or shorter than the solar day, and so becomes increasingly out of sync. This type of cycle would be kept in check by the regulating mechanisms of melatonin and light, but may drift free in a non-light-perceiving individual .
Several studies conducted on the blind report that at least half of non-light perceiving individuals suffer from circadian rhythm sleep disorders . These non-light perceiving individuals report difficulty going to sleep, waking, and staying awake throughout the day, as the rhythm of their biological system doesn’t correspond with the environment . Digestion and metabolism may be disrupted if meals are consumed during the biological night, leading to increased levels of glucose, insulin, and fat after meals. This may cause an increased risk of diabetes and heart disease . Irregular sleeping patterns can also interfere with normal life. Some choose to sacrifice their social lives and work in order to follow their own internal clocks. This choice enables them to function at full capacity, but prevents them from matching their schedule with those of their family, friends, and co-workers . Others choose to find medication and treatment to fix their circadian rhythm so they can better integrate with society.
While stimulants and depressants can force a patient to sleep at certain times, they only address the symptoms and not the misaligned circadian rhythm . Strategies for treating the root of the problem suggest administering melatonin, which has been shown to correct free-running circadian rhythms disorders as well as delayed and advanced sleep onset disorders . Patients are told to take the hormone a few hours prior to the desired bedtime, mimicking the normal cycle of melatonin. This has worked for numerous patients, although those with extremely deviant cycles may not respond to treatment. Recent developments have provided similar strategies using drugs such as Ramelteon, which mimics melatonin but is designed to target MT1 melatonin receptor with greater affinity than melatonin to induce sleep onset. Alternative strategies without medication include non-photic entrainment, in which a rigid daily routine is maintained to try to keep the circadian rhythm in sync .
Circadian entrainment provides a great many benefits, and occurs naturally with the rise and fall of the sun. Yet, many people in the modern age do not take advantage of their circadian rhythm, disrupting the natural cycle by staying up far past dusk with electronic devices . Through continual exposure to light, people desynchronize their circadian rhythm voluntarily; instead of operating under constant darkness, they work under continual light. Take advantage of the system provided through nature, but don’t turn a blind eye to the clock.
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