So far in this first lecture, you've heard about rhythms of various lengths from very short ones to very long ones. You've learned what is a circadian rhythm and you've heard how it shapes the ecology of a simple organism. In this case the marine unicell <i>Gonyaulax</i> now I'm going to tell you about many examples of circadian or daily rhythms from different branches of the tree of life. From animals, plants, fungi and cyanobacteria. We'll start with the animals, and the first example that I want to tell you about is circadian rhythm in humans. This makes it all so real. Take a minute to think about how you would set up such an experiment. How can you measure circadian rhythms in humans? Remember that this is all about rhythms in constant conditions and our environment is filled with zeitgebers In fact some very brave pioneers in our field of chronobiology went in to find constant conditions in caves. In caves, both light and temperature are relatively constant, although very unpleasant. In the modern era we use so-called temporal isolation facilities. These are rooms or apartments that are isolated from the outside world. There's no clock on the wall, there are no windows to the outside, and no noises come in to indicate time of day or night. The first of these facilities was actually built very near here outside of Munich by Jürgen Aschoff as part of his Max Planck Institute. In his bunkers, Aschoff had 100s of subjects live for a month at a time following various protocols. This graph shows you one such experiment. First a word about how this graph is set up. Day one is at the top, and day 30 is at the bottom with one day graphed across on each line. At the bottom you see local time graphed as three days, so that we can follow the free running rhythm as it either runs shorter or longer. In this graph we'll show you the onset of sleep for the duration of the whole experiment. In this protocol, the subject was allowed to leave the door open for the first week of the experiment. You see, he sleeps at about the same time each night, about midnight. On the eighth day the door is closed. Temporal isolation. After some reorientation the daily onset of sleep occurs about 25 hours later each day. He has a free running period that's longer than 24 hours. This was typical for the subjects in these bunker experiments. After two weeks of isolation, the door of the bunkers opened, in this particular protocol, and the subject tries to entrain to sleep at about midnight again. I like this experiment, because it clearly shows the important circadian clock properties of both entrainment, or synchronisation, to the environmental cycles. And also the free running rhythm that you see in <i>Gonyaulax</i>, Apparently we're just like other clock model systems, what else does the human clock regulate? You'll find extremely diverse items here from cognitive function all the way to constituents of urine. Some of these were measured in the presence zeitgebers and in a daily cycle where subjects slept. In these experiments subjects come into the lab and are kept quiet mostly lying down. Here you can see some examples of circadian rhythms measured in this way. The first graph shows core body temperature. It's almost a degree higher during the day relative to what it is at night. Second the concentration of the hormone melatonin is elevated at night and low during the day. Melatonin is used by some researchers as an indication of where the internal clock is at a given moment. A phase marker. The third graph shows the change in heart rate during the day, from higher in the subjective day, to lower in the subjective night. Obviously humans are not great for actively dissecting the circadian clock mechanism. This is where model organisms come in, and the most important model for the mammalian clock is mice. As a model system we appreciate that mice are small. They're relatively cheap to maintain. They have a long history of genetic studies and thus a lot of defined genetics associated with them. Their genome is sequenced. And there have been several large-scale mutagenesis studies that routinely deliver us a set of mutant mice. We'll hear more about these in the lecture on molecular mechanisms of the circadian clock. So what do mice do that's regulated by their circadian clock? Like humans, sleep and activity. I'm going to show you this with the help of a very long experiment that followed a mouse through different conditions. The first part of the graph shows a standard light dark cycle with 12 hours spent in each condition. Then moving down into the graph each line across represents one day. And the activity of the mouse is marked with vertical black lines, so a lot of activity looks like dark blocks on the graph. The first thing to note is that the mouse is nocturnal, in contrast to humans. You might also note the sharp onset of activity each day. The next block of the graph shows release of the mouse into constant darkness. Here the activity starts earlier each day meaning that the circadian rhythm in constant darkness or DD is less than 24 hours. The next part of the experiment calls for about ten days of re-entrainment in a light dark cycle, after which the animal is released into a different constant condition, namely, constant light. Moving from low light to high light you see that the mouse shows a free running rhythm longer than 24 hours in this case. And that this increases further with increasing light. At high light levels the animal becomes arrhythmic. This is typical for possibly all animals, but they eventually become non-rhythmic in high levels of constant light. What else is rhythmic besides activity in mice? In this experiment, temperature was measured, and you see that it mostly follows the activity levels faithfully. You also recall that in humans, there are many and diverse functions that oscillate according to time of day. This is also true in mice. And here, you can see a graph that indicates that olfactory discrimination, the sense of smell, it's higher at night than in the day. To be more accurate, because this experiment is done in constant conditions, we call this, subjective night and subjective day. [SOUND]
