SAD and the brain's calendar

The body doesn’t just keep time with clocks, it also uses calendars. And the changing seasons can mean that the amount of light available is in short supply in the winter months. Estimates are that around 6% of the UK suffer severely from seasonal affective disorder. It’s a type of depression that comes and goes with the seasons, and up to 80% of sufferers are female. But exactly what’s going on in the brain of people suffering isn’t well understood. Now, scientists at Marquette University in the US have found that, when the brain’s internal calendar gets stuck in a summer mode, perhaps this can prevent SAD, and this might be what’s happening to everyone not affected by the condition. Chris spoke to study author Jennifer Evans to find out more...

Jennifer - 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 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 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, they're signals the rest of the body. When the signal is short, it's winter. And when it's long and spread out in duration, then it's summertime.

Chris - 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 spread out over a longer period of time in the summertime? But in the wintertime it's a narrow focus, signal on signal off?

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

Chris - 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?

Jennifer - No, they're not all clones of one another. And we can recognize 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 specialized 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.

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

Jennifer - 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 light input from the eye directly, but then it transmits and communicates this information to 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.

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

Jennifer - Well, we used a genetic trick that was developed 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 produces. More importantly, we can take pictures of hundreds of cells all at the same time. So we can see kind of how they're co-ordinated in space and time as a population. And so we exposed 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 co-ordinated 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 8 to 12 hours later the other group will turn on. And so they're normally unified, but in the summer they break into these two very different groups that are representing these specialised cells.

Chris - It's like having a watch on each arm, and the watch on the right arm goes forwards, and the watch on the left arm goes backwards. They are sort of the mirror image of each other.

Jennifer - 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.

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

Jennifer - 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 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. 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.

Chris - Is it that when the days become very, very long, actually it's quite easy for the clock to get dis-regulated 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?

Jennifer -That's a possibility.