How the brain keeps track of the seasons

你是这些人中的一员,害怕出现of winter with it’s short, dreary, grey days that make you miserable and in the mood to hibernate? If so, you might have the appropriately-named SAD syndrome - seasonal affective disorder. Characteristically with SADS, symptoms of depression kick in as the days shorten, and relief only comes with the return of the sunshine in spring. But why does this happen, and what can we do about it? Speaking with Chris Smith, Jennie Evans, at Marquette University, has made the intriguing discovery that the nerve cells in the brain’s body clock - known as the suprachiasmatic nucleus - split into two separate timing devices in summer, producing much more prolonged timing signals. Locking them in this state might help to ward off SADS…

Jennie - The take home of our work is that if the brain becomes stuck in a summer mode, it may be a way to avoid catching the winter blues. There's a small part of the brain that basically acts as a calendar. It keeps time and orchestrates what our bodies do over the 24 hour day, making sure that we wake up at the right time and our hormones get turned on at the right time and we eat at the right time. And it receives light information from the environment like the sunrise, so that it's kind of set to local time and also the season.

克里斯- How does it keep track of seasons? I can understand how it could track a day, because it's got the sun rising and the sun setting and that's a fairly potent regular stimulus, but how does it know when in the year we're at?

Jennie - It knows what time of day it is because the cells of this part of the brain make certain proteins and so the proteins get turned on and then they turn themselves off. So you can tell what time it is just by knowing how much of this protein is made at any given time. The way it tracks seasons is slightly different: it's the whole group of cells that act together and kind of coordinate with one another. So in the winter they're doing the same thing, at the same time. And so it's kind of the short brief signal to the rest of the body and that matches the, you know, short days of winter. But in the summer when the days get longer, these cells kind of "spread out" and they're doing things at slightly different times. So, as a group, their signals to the rest of the body, when the signal is short, it's winter. And when it's long and spread out in duration than it's summertime.

克里斯- You don't mean the cells physically change position? You mean as in the stimulus, the signal that they are emitting to the rest of the brain and the rest of the body is, is spread out over a longer period of time in the summertime. But in the winter time it's a narrow focus signal on signal off.

Jennie - Yes, exactly. So it's the duration of this signal and winter it would be short and in summer it would be long.

克里斯- Are all the cells in the body clock the same except they behave differently; or actually are there different populations of subtly different nerve cells in there? So it's natural for them to divide into subpopulations and have this more smeared-out function when the days get longer?

Jennie - No they're not all clones of one another. And we can recognise and kind of classify them into different groups based on the chemicals that they produce. So every single cell in the brain's clock can tell what time of day it is, but they express specialised chemicals and proteins that we use to kind of classify them into different groups. And they tend to form two main clusters that we can distinguish chemically.

克里斯- And what are those clusters and how does that affect the behaviour of the whole population in summer compared with winter?

Jennie - The two clusters, we tend to kind of distinguish them chemically and spatially. There's a core cluster that's kind of in the centre of this structure, and this is the part of the clock that actually receives the light input from the eye directly. But then it transmits and communicates this information to kind of the surrounding cells. And so it's these two main clusters, the light receiving group versus the downstream group that separate and reorganise their relationships in summertime.

克里斯- How did you make this discovery then? How did you identify that you've got this going on?

珍妮,我们使用遗传de技巧veloped by Joe Takahashi. They used a firefly enzyme and they attached it to a protein that's made every day. And so we can tell what time of day it is in a cell. All we have to do is take pictures of how much light it is producing. More importantly, we can take pictures in the hundreds of cells all at the same time. So we can see kind of how they're coordinated in space and time as a population. And so we expose this special transgenic mouse to either a standard laboratory condition, or these long summer days. And so under the standard condition, the cells were nicely coordinated and synchronised, basically doing the same thing at roughly the same time. But, in the summer, these two spatially-distinct clusters of cells do very different things. And so what happens is they're basically working opposite shifts. So one group will turn on, and they'll glow, and then they'll diminish; and then eight to 12 hours later the other group will turn on. And so it's kind of, they're normally unified, but in the summer they break into these two very different groups that are representing these specialised cells.

克里斯- It's like having a watch on each arm, on the watch, on the right arm goes forwards, the watch on the left arm goes backwards there. There's sort of the mirror image of each other...

Jennie - That's a really nice analogy. So what I would say is it would be like, yes, having a watch on both arms and one might be set to Hong Kong time and the other would be set to 12 hours later.

克里斯- But why would the brain want to do that? What's the benefit of that?

Jennie - We don't yet know enough about what these two groups are doing and how they're communicating. So it may be the case that one group of cells kind of starts - and so it's kind of like "turn on". So maybe it communicates with the structure downstream that controls your sleep and it says, "Hey, wake up!" And then the other group of cells, 12 hours later says, "Go to bed!" So they may be very distinct in terms of the types of signals that they're providing, and if they're spread out in time, then you would have sleep grow longer or shorter. Um, so that's, that's kind of speculation. We don't exactly know why it would adopt it this way. And I think really the heart of it is we need to know more about what these cells are doing and how they're communicating with the other parts of our brain and body.

克里斯- Is it that when the days become very, very long, actually it's quite easy for the clock to get dysregulated because actually when you should be going to bed, you might not feel the urge to go to bed because it's still quite light. Whereas if you've got a double push, a clock to wake you up in the morning, but one to put you to bed at night, it can overcome some of the difficulty of having a very long bright day?

Jennie - That's a possibility.