How social isolation changes the brain

During the coronavirus pandemic, we've mostly had to isolate ourselves as much as possible. But what effect could this be having on our brains? Researchers at University College London have been trying to answer questions like this using teenage zebrafish. The advantage of zebrafish is that they're transparent, so you can see what is changing in the brain, as Eva Higginbotham heard from Elena Dreosti...

Elena - So zebrafish are the fish that we use in the lab, and they're very tiny fish. And I'm sure that everyone has seen them because they are usually bought as pets and they are kept in aquariums. Like many fish they're very social. So they all swim together and they like to stay together. And they establish a lot of different hierarchies within their own groups. So what we are interested in our lab is basically to understand what happens when we're deprived of other humans, and in fish clearly deprived of other fish. As you know, in a normal population, we have people that are very shy and people that are very easygoing and bold. And that's exactly what we found in a normal zebrafish or fish population. And usually what we have is that 10% of the fish are very shy and very aversive to the other fish.

Eva - How do you know if a fish is aversive or social?

Elena - Yeah, what we do is very simple. So we have a simple arena where a fish, they can choose between two different sides of this arena. They can either stay near other fish and they see this fish through a glass slide, or they can decide to be on the opposite side of this arena, where there are no other social cues. And depending on how much time they spent on one side or the other, we divide them into very social fish or a fish that are aversive. And what we did is basically we isolate the fish for 24-48 hours, so a very short period of time, but also for a much longer period of time. And then what we did, we took the brain of this fish, and then we put it under a microscope and we imaged the whole brain and we could see at the level of single cells. And so we have a proper, very high resolution. And at that point we could perfectly understand what are the areas that were different between a fish there were either social or non-social, and then the differences between the fish that were isolated.

Eva - And what did you find?

Elena - So what we found is that when we isolate the fish, what happens is that this behaviour of being aversive increases and there is a much larger population of fish that become aversive to other fish. So the beauty of using zebrafish is that they are transparent, fully transparent, and we can see through their brain. And then we can actually record the activity of each single cell, each single neuron, of the brain with a very, very high resolution. What we saw is that some areas that are either very specific and involved in social interaction were very different compared to aversive fish and social fish. And then there were also areas that were involved in the reward. For instance, one of them was the hypothalamus and these areas were also very different compared to isolated fish versus normal fish.

Eva - In what ways were they different?

Elena - In the case of the normal population, the hypothalamic area is either very activated in case of prosocial fish, whereas the loner fish are not, they don't have this increase of activity. And this is probably because these fish, they do not have this experience of reward from the presence of other fish. But what we did see in the isolated fish in this case is that the areas that were mostly activated were areas associated with stress and anxiety, and this was not the case in a normally raised loner fish that are normally aversive.

Eva - I see. So the naturally shy ones don't have the decrease in activity in the hypothalamus, but the isolated fish that have been sort of made to become shy, they did see the change.

Elena - Exactly. So what happened is basically that if you isolate the fish, you have an increase in activity in areas that are activated with anxiety and fear. And this is not the case in fish that are normally aversive to the presence of other fish.

Eva - Did you find that they could recover from being isolated?

Elena - Yes. What we saw is basically that if we treat the fish with a drug that reduces anxiety, then the fish, they do recover almost fully their social behaviour. The drug that was used is called buspirone and it's a drug that is used in humans to reduce anxiety. What it does it basically increases the level of serotonin and that's the way that in humans it acts to reduce the anxiety.

Eva - This study seems very appropriate considering the coronavirus lockdown times that we've all been living through for the last few months. Do you think that there's anything we can learn from this study as to how humans react to social situations after they've been sort of deprived of social contact for awhile?

Elena - Yes. I think definitely. Because what we saw is something that we thought it was at the beginning counter intuitive. In fact, if we put fish in isolation, we would expect that they were more likely to be willing to be near other fish. But instead what we see is that there is an increase of anxiety and fear in response to social cues. And what I think could be the take home message is that, especially right now that we all are experiencing this lockdown, is probably we're going to be a bit more anxious when starting to return to our normal social lives. But I think what we should do, and what we learned from zebrafish, is that we should just start to go out and start to meet other people and trying to get over this anxiety, this first level of very stressful response to the presence of others.