Sleep 8.2 The Suprachiasmatic Nucleus: The Body’s Master Clock

Name: Sleep 8.2 The Suprachiasmatic Nucleus: The Body’s Master Clock
Uploaded: 2025-11-25T08:41:49.561Z
Duration: 10:54
Description: Explore the structure and function of the SCN, its critical role in synchronizing body functions, and the impact of light on these processes.

Explore the structure and function of the SCN, its critical role in synchronizing body functions, and the impact of light on these processes.

Video Breakdown:

00:00 Introduction to the Suprachiasmatic Nucleus (SCN)

00:43 Functions and Importance of the SCN

01:36 SCN Synchronization Mechanisms

02:38 Intrinsic Circadian Rhythms

03:55 Role of Light in Circadian Rhythms

05:04 Impact of Modern Lighting on Circadian Rhythms

06:02 Melatonin Suppression by Light

07:50 Molecular Mechanisms of Circadian Rhythms

09:11 Phase Response Curve and Clinical Relevance

So the next topic I'll talk about is the central clock or the suprachiasmatic nucleus. Now the suprachiasmatic nucleus or the master clock is located right here, right below the third ventricle, and you'll see that the optic chiasm is located here. And then there's two nuclei each above the the optic chiasm.
Each nuclei has about 10,000 neurons and as we know, this is the principal circadian pacemaker for the entire organism. And its primary role is to interpret environmental light cues and transmit timing information to the rest of the body. And from there, the SCN coordinates a wide array of outputs.
It provides outputs to the local brain clocks that shape, cognition, mood, and brain homeostasis. It also sends autonomic and endocrine signals that regulate blood pressure, glucose, and also provides systemic cues like, body temperatures and feeding cycles. This makes the SCN not just a timekeeper, but the central hub that ensures the entire body stays synchronized with the external environment.
Now, the SCN is part of the anterior hypothalamus and it's considered necessary. So if you damage the SCN, either by ablation or tumors, this disrupts the circadian rhythm for the whole body. And it is also considered sufficient for the circadian rhythm because if you transplant an SCN from one organism to the one that had the ablated SCN this restores the rhythms, to that animal as well.
And so what makes the SCN special is how these cells synchronize with each other. On the left, you see isolated SCN neurons for each one has its own rhythm, but they're noisy and imprecise, with the cycle variability of over an hour. And on the right when neurons are connected in a tissue slice or within the whole or animal variability drops just dramatically.
And that's because the SCN neurons use multiple layers of coupling: electrical connections through gap junctions, chemical signaling via neurotransmitters like VIP and GABA, and also supports from astrocytes which release glutamate. So when all of this scales up to the whole animal, the system becomes incredibly precise with the cycle standard deviation of only a minute, only minutes.
And so this collective synchrony is what allows the SCN to reliably orchestrate the rhythms across the whole organism. And so, even without external cues, the SCN generates an intrinsic circadian rhythm. And this study, which is a pivotal study done by Chuck Czeisler in 1999, was done under forced desynchrony, where light exposures was tightly controlled.
And this measured circadianperiod using melatonin, cortisol, and body temperature. And so the average intrinsic period was about 24.18 hours, just slightly longer than 24 hours day. And I think that's why the daily environmental time cues, especially light, are necessary to reset the clock and to keep us aligned.
And interestingly, you could see that there is some variability between individuals and even slight differences between younger and older adults. This individual variation intrinsic period partly explains why some people are naturally tends to be morning larks or night owls. And this study actually corrected the original thinking, at that time, which was the belief that the circadian rhythm ran about 24 hours.
And this was the bunker studies done by Aschoff in the 1960s and 1980s. But that was contaminated by light. So, clearly I think the intrinsic rhythms we know at least in humans is about 24 hours. So now light activates signals originally, so this is an image of the retina and a zoom up picture of the retina.
You could see various components of the retina here. You could see the cones, which detect color, and rod, which detectsthe details of lightvision. And then you have, these RGCs, the retinal ganglionic cells, which synchronize the data that you get from these rods and cones. About one to 3% of these RGCs are what's called ipRGCs, intrinsically photosensitive RGCs.
And they're only about 5,000 ipRGCs per retina. Now these ipRGCs were found to be critical for the regulation and detection of light for the circadian rhythm. And, within the ipRGCs are something called melanopsin. And Melanopsin has the peak sensitivity or the absorption of light at about 480 nanometers, which is the scion blue. Interestingly, this is, of some significance, in our modern lifestyles, because what we've seen is that in the past when we've had incandescent light, there's been a predilection or favoring for mostly red or orange part of the spectrum. Fluorescent lights, had, you know, sort of bands that went all over the place.

But, it certainly didn't affect that much on the blue side. However, when we have the LED lights, particularly the cool white lights or the daylight LEDs, you see a peak of the intensity of the light, particularly in this blue region, which matches the absorption that you see at the Melanopsin.
And so we see that some of the modern development, particularly with the LED lights, which is aimed to save electricity, can affect our circadian rhythm as a result. Our retinas are extremely sensitive to light. And so this is a study, published by Phillips Andrew Phillips in 2019.
And the top panel shows the average melatonin suppression across all participants at different light intensities for the overall data and for each first three hours after DLMO, which is the dim light melatonin onset, which is about two hours before the onset of sleep. And so this curve indicates that melatonin suppression increases with light intensity with the ED50, which is the effective dose for 50% suppression values marked for each condition.
So overall, ED50 is about 24.6 lux, indicating a pretty high sensitivity light. And, just to give you some context, a full moon on a clear night provides a lux of about 0.1 to 0.3 lux, exposure to smartphones in the dark settings, that medium brightness is about five to 30 lux. So you could already see just watching the smartphone, or taking a look at the smartphone at night, leads to suppression of about 50% of the melatonin.
Then if you have street lights or even bright lights, it's much larger here. You can see that there is greater sensitivity in the first hour after DLMO, and then a little less so afterwards. This middle panel also displays the significantvariability between individuals. Each curve represents one participant with colors ranging from blue for the most sensitive or, in other words, lowest ED50, to red with the least sensitive.
And so this wide range of individual responses demonstrates that some people are highly sensitive to dim light, while others require much brighter light for similar melatonin suppression. Now at the molecular level, circadian rhythms are driven by what's called the transcription translation feedback loop, or TTFL.
This is a fundamental mechanism inside the SCN neurons that generates the 24 hour cycles. And here's how it works. So the proteins like CLOCK and BMAL1 activate the transcriptions of target genes such as Per and Cry. And these Per and Cry accumulate in the cytoplasm. They get phosphorylated and they get brought back into the nucleus, which then subsequently leads to the inhibition of its own transcription. This whole cycle, so there's a delay, so this happens about 24 hours to complete. You also have additional regulators like REV-ERB, RORs to fine tune this process while network inputs like light through the retina or neurotransmitter signaling help reset and stabilize the cycle.
And so this result in a self-sustaining molecular clock at each SCN neuron with tightly orchestrated rhythms in iron conductance, calcium signaling, and gene expression across the day and night cycle. And you can see here just to see how this enables activity, based on the phase of the day.
This is the phase response curve and this describes how the timing of light exposure affects the direction and magnitude of your circadian phase shift. The horizontal X axis is the biological time relative to the habitual sleep period. Negative values here, hours before natural sleep, basically shows the time before you go to bed, the positive means afterwards.
And the y axis here, this signifies the phase shift magnitude and direction. So a negative value is phase delay, in other words, the circadian clock moves later. And the positive values indicate phase advance or circadian clock moves earlier. And the key findings here is that from minus three hours into five hours into sleep, light exposure shifts the circadian rhythm later. This results in harder time waking up in the morning. And this larger phase delay is about two hours before natural sleep onset. So this is clinically relevant. It coincides with a typical evening electric sort of electronic device use. There's also a phase advance region, which occurs in the last three hours of sleep and the early waking hours.
And so that may be why it's advantageous to expose yourself to the light, and makes it easier to wake up in the morning in the following days. And then there's the crossover point, which is about two to three hours before natural wake time. This aligns with a core body temperature minimum as well.

Course episodes

Sleep 8.1 Introduction to Circadian Physiology

Sleep 8.2 The Suprachiasmatic Nucleus: The Body’s Master Clock

Sleep 8.3 Peripheral Clocks: Synchronizing the Body Beyond the Brain

Sleep 8.4 Systemic Zeitgebers: How the SCN Coordinates the Body

Sleep 8.5 Non-Photic Zeitgebers: Meal Timing, Exercise, and Metabolism

Sleep 8.6 Understanding Process C and S in Sleep Regulation