Saturday 28 May 2016

Memory Tests for Mouse Lemurs

The ability to learn and remember things is a vital ability for just about any animal, albeit the sort of things that (say) monkeys are able to learn can be a good deal more complex than those flatworms can manage. There are, however, multiple different types of memory, rather than it being a single process that takes place in our brains and works the same way every time. There is the difference between short-term and long-term memory, for one thing (and there's actually more than two of those), but also between what are termed procedural and declarative memory.

Procedural memory is the ability to remember how to do something. Once you've learned whatever the task is, you don't need to think about it, it just comes automatically, like riding a bicycle. Exactly like riding a bicycle, in fact. Declarative memory, on the other hand, is the sort of thing you have to think about, such as remembering what happened to you the last time you were in a specific situation. If you're a human, this includes the ability to remember things like Vespertilio being a genus of bat (well, it is if you're me), but it also encompasses a much wider range of knowledge about the world and your own experiences in it.

If you want to test how well an animal learns and remembers things, it's generally a good idea to teach it the sort of thing that it would learn in the wild. For instance, the reason we keep putting mice in mazes to study their learning abilities is that running around through potentially complex series of tunnels and natural passages is exactly the sort of thing that mice do all the time anyway. Sometimes, however, scientists haven't quite got the hang of this.

Take this experimental method from 1930, for instance. The experimenter here wasn't so much interested in how well his rats could remember which of a pair of symbols was the "good" one, as to whether or not they could tell them apart in the first place, but the principle is the same. Here's how it works: you place your rat on a raised platform, and in front of it there are two windows with dinner behind them, marked with different symbols. To get to the windows, the rat has to jump over a gap, hurling itself at its target.

The rat, being a rat, and therefore not very keen on long jumps, doesn't particularly want to do this. So we send an electric shock through the platform, forcing it to leap at one or other of the windows, since it can't stay where it is. If it picks the correct window, it swings open and the rat finds itself on the other side, with the dinner. Hooray! If it picks the wrong one, it discovers that the window is locked, whacks itself hard on the immovable surface, and plummets down into the chasm beneath, where it is caught in a net.

You can't really argue that the rat isn't motivated to learn which window is the one that will open, but it's not the sort of experiment we'd be terribly keen on doing today. However, a modern version of the same experiment has recently been devised, and used to test learning and memory in grey mouse lemurs (Microcebus murinus).

Mouse lemurs are the world's smallest primates; at just 60 g (2 oz.) they are even smaller than pygmy marmosets, which are the smallest monkeys. This makes them a good deal cheaper to keep and feed than, say, rhesus macaques, let alone chimpanzees, but they're still primates, and do (as we'll see) have some useful things to tell us about our own species.

Until 1998, we thought that there were two species of them, but we now know there's about two dozen - which is the sort of thing that happens when you have very small animals that all look pretty much the same, live in the depths of the jungle, and only come out at night. Many of them are endangered, but the grey mouse lemur is actually quite common, making it a more suitable experimental animal than most of the others.

The basic set up of the new experiment is similar to the old one: you place your mouse lemur on a platform, across a wide gap from two other platforms that lead to a cosy nest that they can sleep in and not be disturbed. The first advantage, though, is that mouse lemurs, since they live up trees, are animals that really like to jump, so you don't need to electrocute them to get them to do so. Nonetheless, in case they're not in the mood, should they just sit there, the platform they are on slowly starts to tilt, and eventually they will have to leap if they don't want to fall off.

The two platforms on the other side of the gap are marked with different symbols - since, in this case, we want to test their learning ability, not how well they can tell symbols apart, we make them as different in colour, shape, and material, as we possibly can. One of the two platforms, however, is unstable, and if they land on that one, they will drop onto a nice soft pillow, where an experimenter picks them up for another go - but they don't get their uninterrupted kip in a cosy nest.

Which is a significant improvement over the original, from the animal's point of view, and has some resemblance to what mouse lemurs do in the wild anyway. (It's hard to imagine, for instance, that they don't occasionally land on a branch that isn't as stable as they thought). It's perhaps because of this that the mouse lemurs did very well on the "learning" part of the test. All twenty of the animals got the hang of the test quickly, and certainly quicker than mouse lemurs have learned how to do memory tests that required them to use touchscreens, or tell different smells apart.

But it's with the second part of the test that we get to why the researchers wanted to use mouse lemurs in the first place. After training the animals which platform to jump onto, they then left them for a month, before putting them back into the apparatus and testing them again. Would they remember what to do, or would they have to learn it all over again?

Yes, they could remember, some of them getting it right almost immediately on the second attempt. Testing them again using a different pair of symbols had a similar effect - they learned which symbol was the right one in about half the time that they had before, apparently able to remember how the test worked and only having to re-learn which symbol was which.

But they didn't all do equally well. Although it didn't take them any longer to learn how to pass the test in the first place, one group of animals struggled a little trying to remember things a month later. They still got it right in the end, and more quickly than they had on the first attempt, but they made three times as many mistakes before doing so than the other group did.

What was the difference between these two groups? Simply put, the ones that had a hard time remembering what they'd done last time... were older. In fact, they were over twice as old as those mouse lemurs in the "young" group - seven and a half years on average, compared with just three and a half years. Which, since mouse lemurs don't live more ten years at the most, is actually quite a difference.

If you're a mouse lemur, it seems, the older you get, the harder you find it to remember new things. Now doesn't that sound familiar?

Learning itself isn't a problem, their minds seem just as agile as ever; it's just trying to remember the exact details of what happened a month after the fact. There have been numerous previous studies showing this sort of thing in mouse lemurs, and it's precisely why the researchers had wanted to use these animals rather than monkeys. Few other primates live as long as humans do, but a maximum ten-year lifespan is particularly short - chimpanzees, for instance, can live for up to 59 years.

It's not just that; mouse lemurs' brains change in a similar way to ours as they age - just far more quickly. Elderly mouse lemurs develop brain lesions very similar to those seen in humans suffering from Alzheimer's, and parts of their brain atrophy in similar ways to ours, leading to clearly identified cognitive decline. It's entirely probable that we'd see something similar if we looked at other primate species in the same detail, but, so far, they're the only ones we have, and their short lifespan makes it easier to do.

So an experiment with jumping mouse lemurs might be a tool that, in the longer term, could help us with our own ageing population.

[Photo by Arjan Haverkamp, from Wikimedia Commons.]

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