eLife episode 25: Sleep and Reward Boost Recall

Thanks to decades of effort, Richard Doll and his colleagues proved that smoking is bad for your chest. In fact, the lungs of very heavy smokers become stained black or brown with carbon deposits. But no one knew whether this was a cause, or just a consequence of various smoking-related conditions like emphysema or chronic obstructive pulmonary disease where sufferers find it progressively more difficult to breathe. Now Farrah Kheradmand, at Baylor College in Texas, has discovered what that brown pigment is. By exposing mice to a pure form of it, she can trigger lung disease identical in many ways to that suffered by smokers and coal miners. And it looks like a major culprit in chest disease is just carbon...

Farrah - The story began when a graduate student in my lab isolates a particular cell type from the lungs of humans who've smoked.  That particular cell just appears to be dark in colour and repeatedly he came to my office and showed me these cells, and repeatedly I very much explained that this is what's been explained in pathology text books, that smokers collect dark material within their lung.  So his next question for me "what was the origin of this dark material" and I referred him to pathology text books that describe this as anthracotic particles, the nature of which was rather elusive and so he went on to disintegrate the cells, the result of which ended up being a very fine material that really wasn't visible by naked eye.  That's when we contacted our colleagues over at Rice University, they decided to give the composition a try. Try to understand what the chemical nature of this dark material was.

Chris -   So what was that dark material?  When you look in those cells, the stuff that's staining them black, what is it?

Farrah - When I got a phone call back from our colleagues at Rice University, their first question was "where did you get these fine particles of 15 nanometre?" which is 15 billionth of a metre.  Very small particles that are pure elemental carbon black.

Chris - So how did you then tie the presence of these particles in the lung to the disease process because they could just be there as an innocent bystander?  The fact that they are in the smoke that the person breathes in doesn't mean necessarily they are connected to the disease process, does it?

Farrah - The connection with the disease process was the particular cell types that these nano-carbon black particles collect in.  In fact, if you take the same cells isolated from the lungs of mice that have been exposed to cigarette smoke, and transfer these cells to naive mice, meaning mice that have never seen cigarette smoke in their lives.  A similar pathology starts happening in their lungs, meaning that there's quite a bit of inflammation and changes that are consistent with a smoker's lung is now shown in the mice that have never seen cigarettes.  Therefore, for the first time, it connected a particular cell to disease formation

Chris - How do you think those - literally just little particles of carbon - are causing the disease then?  What are they doing to the cells that they end up in that leads to that disease both perpetuating in one animal, but also the ability to transmit that disease to another?

Farrah - When nano elemental carbon black accumulates in these cells, these cells become activated to try to undo the damage, meaning they are now encountering a danger signal that they are trying to alleviate, and therefore they turn on a whole programme of genes that we have identified, some of which are important in DNA repair damage for instance. When they turn these genes on the result of which results in an activated cell that then can direct the cells of your immune cells, cells that are normally there to protect you against foreign invasion or dangers, that can result in inflammation in the lung.

Chris - How do you know that it's the carbon particles that are doing that per se and not, for instance, something stuck to the carbon particle, because when they come into the body they are going to be laden with other hydrocarbons and other materials from the burning cigarette or whatever other forms of pollution you have been encountering, aren't they?

Farrah -   This is an experimental model where we had access to highly purified elemental carbon black that was devoid of any material that could have possibly been attached to it, and were all experimentals that were performed in my laboratory used particularly a form of the elemental carbon black that is 99.99 percent pure

Chris - It seems very surprising that given the ubiquity of fine particles of carbon in the environment that the lung hasn't evolved a way not to respond like this to clean itself out.  Why do you think that's the case?

Farrah - Well, in fact the lung does clean itself out, for the most part, and this is perhaps the reason why we find these heavy stained dark material only in the lungs of heavy smokers.  It's a matter of the amount of material the lung can handle.

If you want to learn something really well, the advice has always been to "sleep on it". But, according to University of Geneva  scientist Kinga Igloi, it looks like you also need to really value what you want to learn to get the most out of the effect, as he explained to Chris Smith...

Kinga - We knew sleep had an effect on memory consolidation but we did not know how reward and sleep interact, whether there is a selective effect of reward.  We might have thought of it because we generally remember rewarding things better, like for example, the great party you had when you were a child, but it had never been tested how this works in the brain.

Chris -   I suppose the evolutionary purpose of this is to prioritise the retention of information that in some way is likely to benefit an individual in the future?

Kinga - Yes, it is.  In evolution, we will try to remember things that are important, that we will need for our survival, or for a successful life.  So that is why we thought that rewards may help memory consolidation.

Chris - Tell us about the study design.  What did you actually do in order to probe that?

Kinga - So we make people come in early afternoon and learn pairs of pictures, preceded by a dollar coin or a cent coin, and we tell them that the dollar coin items will yield higher reward at the end of the study, so that they will be paid more if they remember the highly rewarded items better.

Chris - And where does the sleep come into it?

Kinga - So after they have learnt it, half of the participants take a nap and the other half stay awake.  During sleep, we monitor their sleep using EEG, which is electroencephalography.

Chris - And then having established that the person slept and what their brain activity is when they sleep or when they remain awake.  You then present them with those cards again and see how good they are at remembering the pairings you asked them to learn earlier.

Kinga - Yes, we show them the same pairs and so we test their memory.

Chris -   Right, well let's look at the sleep first.  Did the sleep improve retention of those memories?

Kinga - Yes, it did.  We had an overall affect of sleep, so sleep improved retention.

Chris - And then if you look at the value attached, was there a difference there too?

Kinga - There is a difference between subjects who slept and subjects who stayed awake straight after, and there is also a difference between highly rewarded items and lowly rewarded items. Subjects, remember highly rewarded items better.

Chris - And even better again if they sleep?

Kinga - Yes.  Then here we have to be clear, at the test point, so straight after sleep we do not have an interaction effect. So, at test there is only straight effect of sleep, so the subject who slept remember items better, and highly rewarded items are remembered better than lowly rewarded items.

Chris - Is this just a short term effect?  Is this something which is manifest only on that day you test them in the laboratory or if you pull people back days, weeks, months later, do you still see a preserved benefit through having had that sleep plus the high reward versus low reward situation?

Kinga - Yes, it is important to stress that we made people come back three months later, so a long time later, and we retested them on their memories and there was still an important effect of reward, and selectively for the group who slept

Chris -   Putting this together then, how do you think this is working and what did you see when you look at the brain activity?  Does that give you any clues as to what the sleep is doing to make this effect manifest?

Kinga - Yes.  What we find is that there is an effect of sleep and of reward, so that you remember highly rewarded items better and we have linked that in the brain to an activation of the hippocampus.  So we find higher activation in the hippocampus for highly rewarded items compared to lowly rewarded items for the subjects who slept versus compared to the subject who stayed awake.

Chris - So, if you want to learn something really well, you need to convince yourself that knowing it is extremely valuable to you and then sleep on it.