Brain basis of bad food memories

Memories of previous bad food experiences that make us ill tend to form fast, and they’re enduring. Going back decades, scientists had shown that two regions of the brain - one concerned with tastes and the other concerned with fear and emotion - are tightly connected and forming these avoidance memories depends upon both, although the exact wiring arrangement wasn’t known. Now Arianna Maffei has found the surprising result that when something makes us sick, the strength of the connections between the two key brain regions loosens. The findings are far-reaching, from helping patients undergoing chemotherapy in hospital to conserving endangered species, as she told Chris Smith…

Arianna - The circuit we looked at is the connection between the gustatory cortex, which is the area of the brain that processes taste - taste is intrinsically good or bad in addition to having its own identity, whether it's sugar or salt, and the amygdala, which is a centre of the brain that is known to process positive and negative emotions. So we know from previous work that these two areas are involved in assigning a positive or negative value to a taste stimulus. And we wanted to know how that assignment happens.

Chris - So in other words, if I had something like an ice cream and I had the ice cream and I concluded I liked it versus if I have something that I definitely didn't like, the assignment of niceness or nastiness is bound up in this part of the brain, the gustatory cortex and its connections to the adjacent amygdala?

奥利安娜——是的。That's exactly how it would work. So the amygdala would assign a pleasant or unpleasant flag to the taste, to the ice cream.

Chris - But what happens if I overdo the ice cream and I end up being sick, and then afterwards I tend to avoid ice cream because I'm thinking I don't like it anymore because it made me sick. Is that circuit bit the one that's being changed here.

Arianna - So this is exactly what we sought out to find. And our hypothesis was that yes, there is a modification in the connection between the amygdala and the gustatory cortex. So when somebody eats something that makes them sick and this very strong memory known as conditioned taste aversion learning is formed, so we really wanted to know how neurons formed this memory and how this memory gets stuck in this circuit.

Chris - So where did you begin?

Arianna - So we began by inducing this form of learning in laboratory animals. We used rats. So what we did is we offered our rats sugared water that they really, really enjoy to drink. And then we associated this sugared water with an injection of a substance - lithium chloride, that make them have a bellyache. And then the next day we offer them a choice between the sugar water and just plain water. And we wanted to see if their preference for sugar has changed. And in fact, they drank a lot more water than sugared water on testing day when the association had been formed.

Chris - And your conclusion from that part of the experiment would be, right, we've got this connection in the gustatory, the taste area of the brain, which originally was assigned an "I like this" message. And after you make the animals feel unwell for a short while, that "I like this" has been turned into an "I don't like this" signal. And you're presuming it's some kind of connection between the amygdala and the taste centre, the gustatory cortex, has changed.

奥利安娜——是的。我们知道记忆已经形成,一个d from previous work where people were making small lesions, we started out with the hypothesis that the amygdala and the gustatory cortex are necessary. And we wanted to see what happens in the connection between them.

Chris - And if you go in and sample those two areas of the brain, can you see either electrically or chemically, any kind of difference in the behaviour of those sites after you've changed the way the animals regard the sugar water so that once the animals start to avoid it because they don't like it anymore, does the wiring change?

奥利安娜——是的。We went to look into whether the connection had changed and we did find a change. What we did find was a surprising change because the hypothesis typically is that when a memory is formed, the connection between two areas or two neurons strengthens. What we did find instead is that the connection between the amygdala and the gustatory cortex had become weaker. So it was exactly the opposite of what we had predicted.

Chris - Now, if that's the case, is it possible to simulate this adversive response by inhibiting or turning off the connections from the amygdala without any kind of making the animals feel ill? So if you just go in and artificially switch off those connections, can you get the same aversive response?

Arianna - We tried that by using a tool that is called optogenetics. It allows us to activate very selectively only a specific connection in the brain. And we implanted an optic fiber in the gustatory cortex. And we tried to make the association between the sugared water and activity that would decrease the strength of the connection between these two areas directly in the gustatory cortex. And indeed what we found is that we could completely substitute to the bellyache with this stimulation directly in the brain. And the next day, the animals would have learned not to drink the sugar water.

Chris - And why does this matter, the fact that you found this, because going back to the 1950s or so, people had made discreet lesions in brains in these areas, and they demonstrated that there is a loosening of this association if you do that - you can prevent this effect happening. So we had an inkling that this was going on, you've confirmed it and proved that that's what's going on independently and via a different way of doing it. But beyond that, are there other implications?

阿里安娜——是的,是非常重要的知道this form of memories are formed from the intellectual perspective, just to know what is the signature of learning in the brain. But from the more practical perspective, for example, we have patients that are undergoing chemotherapy that, as chemotherapy gives them a bellyache in many cases, it can actually form an association between the food that they have eaten before and give them a really hard time in being able to self-sustain and eat the food that they previously like because of the therapy. So understanding how this form of memory works, also tells us strategies to avoid these negative associations in patients for example. Another reason for why this interesting is that this form of learning is conserved across many, many species and in conservation biology ideas that are related to conditioned taste aversion have been applied to try to protect endangered species from predators, for example, by including the medication like the lithium chloride in the eggs of the species that they want to preserve so that the predator, will be conditioned not to go eat them sugar or salt, and the amygdala, which is a centre of the brain that is known to process positive and negative emotions. So we know from previous work that these two areas are involved in assigning a positive or negative value to a taste stimulus. And we wanted to know how that assignment happens.

Chris - So in other words, if I had something like an ice cream and I had the ice cream and I concluded I liked it versus if I have something that I definitely didn't like, the assignment of niceness or nastiness is bound up in this part of the brain, the gustatory cortex and its connections to the adjacent amygdala?

奥利安娜——是的。That's exactly how it would work. So the amygdala would assign a pleasant or unpleasant flag to the taste, to the ice cream.

Chris - But what happens if I overdo the ice cream and I end up being sick, and then afterwards I tend to avoid ice cream because I'm thinking I don't like it anymore because it made me sick. Is that circuit bit the one that's being changed here.

Arianna - So this is exactly what we sought out to find. And our hypothesis was that yes, there is a modification in the connection between the amygdala and the gustatory cortex. So when somebody eats something that makes them sick and this very strong memory known as conditioned taste aversion learning is formed, so we really wanted to know how neurons formed this memory and how this memory gets stuck in this circuit.

Chris - So where did you begin?

Arianna - So we began by inducing this form of learning in laboratory animals. We used rats. So what we did is we offered our rats sugared water that they really, really enjoy to drink. And then we associated this sugared water with an injection of a substance - lithium chloride, that make them have a bellyache. And then the next day we offer them a choice between the sugar water and just plain water. And we wanted to see if their preference for sugar has changed. And in fact, they drank a lot more water than sugared water on testing day when the association had been formed.

Chris - And your conclusion from that part of the experiment would be, right, we've got this connection in the gustatory, the taste area of the brain, which originally was assigned an "I like this" message. And after you make the animals feel unwell for a short while, that "I like this" has been turned into an "I don't like this" signal. And you're presuming it's some kind of connection between the amygdala and the taste centre, the gustatory cortex, has changed.

奥利安娜——是的。我们知道记忆已经形成,一个d from previous work where people were making small lesions, we started out with the hypothesis that the amygdala and the gustatory cortex are necessary. And we wanted to see what happens in the connection between them.

Chris - And if you go in and sample those two areas of the brain, can you see either electrically or chemically, any kind of difference in the behaviour of those sites after you've changed the way the animals regard the sugar water so that once the animals start to avoid it because they don't like it anymore, does the wiring change?

奥利安娜——是的。We went to look into whether the connection had changed and we did find a change. What we did find was a surprising change because the hypothesis typically is that when a memory is formed, the connection between two areas or two neurons strengthens. What we did find instead is that the connection between the amygdala and the gustatory cortex had become weaker. So it was exactly the opposite of what we had predicted.

Chris - Now, if that's the case, is it possible to simulate this adversive response by inhibiting or turning off the connections from the amygdala without any kind of making the animals feel ill? So if you just go in and artificially switch off those connections, can you get the same aversive response?

Arianna - We tried that by using a tool that is called optogenetics. It allows us to activate very selectively only a specific connection in the brain. And we implanted an optic fiber in the gustatory cortex. And we tried to make the association between the sugared water and activity that would decrease the strength of the connection between these two areas directly in the gustatory cortex. And indeed what we found is that we could completely substitute to the bellyache with this stimulation directly in the brain. And the next day, the animals would have learned not to drink the sugar water.

Chris - And why does this matter, the fact that you found this, because going back to the 1950s or so, people had made discreet lesions in brains in these areas, and they demonstrated that there is a loosening of this association if you do that - you can prevent this effect happening. So we had an inkling that this was going on, you've confirmed it and proved that that's what's going on independently and via a different way of doing it. But beyond that, are there other implications?

阿里安娜——是的,是非常重要的知道this form of memories are formed from the intellectual perspective, just to know what is the signature of learning in the brain. But from the more practical perspective, for example, we have patients that are undergoing chemotherapy that, as chemotherapy gives them a bellyache in many cases, it can actually form an association between the food that they have eaten before and give them a really hard time in being able to self-sustain and eat the food that they previously like because of the therapy. So understanding how this form of memory works, also tells us strategies to avoid these negative associations in patients for example. Another reason for why this interesting is that this form of learning is conserved across many, many species and in conservation biology ideas that are related to conditioned taste aversion have been applied to try to protect endangered species from predators, for example, by including the medication like the lithium chloride in the eggs of the species that they want to preserve so that the predator, will be conditioned not to go eat them.