Memory improves with magnesium
Now most of us would probably welcome a better memory if we were offered one. And believe it or not, a dose of magnesium might well be all that’s needed to make that happen, in flies at least! Scott Waddell, at the University of Oxford, is finding that magnesium supplements can boost long term memory. And he’s also uncovered a gene for a magnesium transporter protein that seems to be essential to the process, as he told Chris Smith...
Scott - We teach flies by exposing them to an odour with a sugar reward, and you're effectively training them to expect to find food when they smell that odour. So when you give them a choice between the two odours, they preferentially run towards the one that they expect to find the food with
Chris - And how long does it take a fly to learn? I know how long it takes to train my dog - it depends if there's food involved! How long does it take to train a fly?
Scott - Well, actually only 1 2 minute session is sufficient to form memories that last for days.
Chris - And then you can come back literally days later and they will have remembered what you taught them?
Scott - Yes.
Chris - Goodness, and then how did you bring the magnesium into play then?
Scott - All we did was we fed the flies with food that contained a high magnesium concentration for a few days before we trained them and tested their memory.
Chris - How do you know that it isn't just the flavour? Cause if you're feeding them with something that makes them feel more motivated because they like it, they're in a good mood now, how do you disentangle that from it being actually a physiological effect on the brain biochemistry of the magnesium?
Scott - Magnesium is of course salty. So I guess one of the controls for that is that we fed other salts that were similar, like calcium strontium and they don't have the same effect.
Chris - So you give the flies, or some flies, supplementation with magnesium versus no magnesium. How does it affect their learning and memory then?
Scott - So funnily enough, their learning or their immediate memory seems to be completely the same, but in the flies that were supplemented with high magnesium levels, their long-term memory is better.
Chris - You've therefore got the observation that supplementing with magnesium has some kind of effect on recall or at least establishment of these memories, so then how did you explore that to find out what is underpinning that observation?
Scott - In parallel, we had been looking for genes that were involved in memory persistence in the fly and Yanying Wu, the person that did most of the work in my lab, had actually found a mutation in a magnesium transporter. And so we simply put these two things together - magnesium enhancement of memory, and a potential molecule that was involved in this. And we found out that it actually was involved
Chris - Where is that magnesium transporter expressed? Which bit of the fly brain is involved?
Scott - It's broadly expressed throughout the brain, but it's particularly abundant in a part of the brain that's called the mushroom body, which is a centre that has been previously implicated in memory formation.
Chris - Talk us through then what you think is actually happening with and without magnesium for the flies to have their ability to recall memories affected in this way.
Scott - To be honest, we don't really know why. All we know is that the level of magnesium in the cells, for example of the mushroom body, seems to be higher when we feed the flies magnesium. And that this transporter seems to be involved in allowing this memory enhancement to occur.
Chris - And if you knock out that transporter or temporarily deactivate it, do the flies lose their sensitivity to this magnesium effect?
Scott - Yes. So we can specifically take this molecule out of the mushroom body neurons and then the flies lose their normal extended memory, in addition to the magnesium enhanced memory.
Chris - And does that transporter pump magnesium in or does it pump magnesium out of the cell?
Scott - So this was a bit of a controversy in the field and our data suggests that actually it's involved in magnesium coming out of the cell.
Chris - Well, that sounds a bit strange then doesn't it? So giving more magnesium, nevertheless results in better memory recall - how do you square that circle?
Scott - Yeah, it seems very counterintuitive and this puzzled us a great deal. So when we started to look at using genetically encoded reporters, we were able to see that the magnesium levels seem to fluctuate over time. And that this transporter that we identified seems to be involved in the efflux phase of that transport. So we assume that there's a maintenance of a higher level that occurs that's dependent on this molecule.
Chris - Do you therefore think that high levels of magnesium facilitate learning in the first place, and that then you need it low in order to keep the memory there? Or do you think that in recalling a memory, you need a spike of magnesium, but then the level has to rapidly plummet in order for that message to be correctly expressed? I mean, how do you actually think it works?
Scott - I don't think we have that level of resolution to really give us an idea of specifically what's happening. That's actually one of the things that's somewhat dissatisfying with the study is that there's an awful lot left to do. And that's one of those things. We know clearly that this molecule is involved in maintaining the levels, but as you say, the higher levels giving rise to enhanced memory and the molecule being involved in actually kicking it out of the cells, doesn't really make intuitive sense.
Chris - And I have to ask you, do you take extra magnesium? Have you got a pot of Epsom salts on your desk, do you spoon feed yourself Epsom salts and stay near a toilet in order to gain the benefit of extra memory?
Scott - So it's funny you say that, I've been considering it, I haven't started yet. I knew you were going to ask me that!
Chris - Well, off the back of this interview, I'm now considering it. But as I say, I will remain proximal to the toilet because it has quite a strong osmotic laxative effect, doesn't it?
Scott - Yeah. Well, what my former colleague that actually did some of the initial studies in rodents does take daily magnesium. He's a smart person. It might work.