Our Internal Clock. The Role of the Suprachiasmatic Nucleus in Our Adaptation to Day and Night

During the millions of years that life has developed on Earth, all living things have been exposed to the light-dark cycle generated by the planet’s rotation and the presence of the Sun. Since the Sun provides light and abundant energy, animals use the day-night cycle to organize their activity-rest pattern.

Probably, to facilitate this behavior, a biological clock has developed during evolution in all microorganisms, plants, and animals, including humans, that synchronizes its activity with the daily light-dark cycle. The main property of this clock is that it maintains a 24-hour rhythm of activity even in constant darkness, and synchronizes each time with sunrise.

In mammals and humans, this clock is located in the brain and is called the suprachiasmatic nucleus (SCN) because of its location above the optic nerve chiasm. Through these optic nerves, the SCN receives the light signal from the eyes to indicate the start of the day. The neurons in the SCN are mainly active during the day, even without light. The clock function of the SCN ensures that, even without a change in light and dark, it modifies its neural pattern of activity (day) and inactivity (night).

Neurons in the SCN transmit this day-night signal through nerve fibers within the hypothalamus, an area the size of a walnut at the base of the brain, where most essential bodily functions are organized, such as reproduction, temperature, blood pressure, and water balance.

The SCN influences functions that are primarily related to our activity-inactivity pattern. It stimulates us to be active every morning, so it prepares our body’s physiology for this vital behavioral change even before the alarm goes off. It also promotes the estrous cycle in females or calving at the right time in the day-night cycle—babies are usually born early in the morning.

An example of what is essential for us to be active in the morning gives an idea of the different tasks that the SCN must perform. Just before the alarm clock rings, the SCN is already influencing brain structures to increase body temperature and heart rate, raise blood’s cortisol levels, increase blood sugar, and influence muscles to absorb circulating glucose faster. The opposite happens with all these parameters just before going to sleep.

All of these changes are essential for our health: if our blood sugar level at night is as high as in the morning, we could have diabetes. The same goes for heart rate, blood pressure, or cortisol. Morning temperatures (e.g. high levels) before sleep are dangerous in the long run.

Consequently, all these parameters are monitored with great precision by various sensory areas, both inside and outside the brain. Most interact with the SCN and therefore receive direct feedback on the correct values for that time of day. For example, by eating chocolate or other sweets while watching TV at night, blood glucose raises to levels too high for that time of day. In interaction with the SCN, glucose-regulating brain areas affect our organs, normalizing glucose levels.

Our cortisol levels in the blood illustrate the apparent need for precise rhythms. In the morning they can be at least ten times higher than the minimum values at night, although the variation at a specific time is minimal. In this way, cortisol levels indicate whether the body needs to be activated. At night, when cortisol levels are low, stress induces much higher cortisol levels than in the morning and is consequently much more detrimental to our physiology. These examples indicate the need for a complex feedback system that informs the SCN and other participating brain nuclei about the actual levels of glucose, cortisol, and other hormones, promoting their normalization at that time of day.

OUR INTERNAL CLOCK ADJUSTS PHYSIOLOGICAL PARAMETERS ACCORDING TO THE TIME OF DAY AND IN RESPONSE TO THE CHALLENGES FACED BY THE BODY

Importantly, infections and food shortages or excess alter daytime and nighttime baseline physiological parameters. When fasting, the reference parameters of body temperature and blood glucose are lower at the beginning of the sleep phase to allow energy savings. Therefore, the SCN also plays an important role in interacting with the brain structures that sense our metabolic state. It is worth noting that even during fasting, the SCN prepares us for the onset of the active phase by increasing glucose and temperature, demonstrating that our internal clock adjusts physiological parameters according to the time of day and in response to the challenges faced by the body. The SCN can accomplish this by receiving information about the state of the body. Consequently, frequent breaches of the SCN message, such as working shifts or eating late at night, can lead to the development of cardiovascular or metabolic diseases.

Observations of decreased human biological clock activity in postmortem brains of hypertensive or diabetic patients, compared to same-age control patients, indicate that in these patients the SCN has lost the ability to adjust the body to appropriate physiological levels. Figure 2 provides an example of such a study, comparing the activity of SCN neurons with that of neurons involved in cortisol release. This hormone is usually elevated during hypertension. In hypertension, the number of active neurons in the SCN is reduced. Conversely, the number of neurons involved in cortisol secretion increases, indicating a decreased ability of the SCN to reduce it.

In humans, SCN develops primarily after birth and begins to lose activity after the age of 60, which is coherent with the difficulties of very young and much older people to properly synchronize their physiology. Therefore, maintaining a stable rhythm of activity and sleep is one of the main solutions for a healthy lifestyle.

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