Most zebrafish demonstrate pro-social behaviour, but approximately 10% are 'loner' fish who are averse to social cues and demonstrate different brain activity than their pro-social siblings. However, even typically social zebrafish avoid social interaction after a period of isolation. PhD students Hande Tunbak and Mireya Vazquez-Prada, Postdoctoral Research Fellow Thomas Ryan, Dr Adam Kampff and Sir Henry Dale Wellcome Fellow Elena Dreosti set out to test whether the brain activity of isolated zebrafish mimics that of loner fish or whether other forces were at play.

To investigate the effects of isolation, the researchers isolated typically social zebrafish from other fish for a period of two days and then compared their brain activity to zebrafish who demonstrated aversion to social interaction without having been isolated. The isolated fish demonstrated sensitivity to stimuli and had increased activity in brain regions related to stress and anxiety. These effects of isolation were quickly overcome when the fish received a drug that reduces anxiety.

The differences between loner fish and their siblings were found mostly in the hypothalamus, the region of the brain responsible for social rewards. The loner fish hypothalamus did not demonstrate the same pattern of activation during social exposure as its typical counterparts, indicating that loner fish do not experience rewards in the same way as typical fish during social interactions.

By contrast, 'lonely' fish -- those that demonstrated typical social behaviour and were isolated -- demonstrated hypersensitivity to stimuli and activation of brain regions associated with stress and anxiety. Lonely fish experienced actively negative outcomes from social interaction whereas loner fish simply did not experience reward.

"A detailed view of the zebrafish brain can provide important clues for all of us currently experiencing the effects of social isolation," says Dr Elena Dreosti. Our understanding of the neural mechanisms of social behaviour are limited, but we do know that zebrafish and humans share a fundamental drive for social interaction that is controlled by similar brain structures. Although human behaviour is much more complex, understanding how this basic social drive arises -- and how it is affected by isolation -- is a necessary step towards understanding the impact of the social environment on human brains and behaviour. The zebrafish, which is completely transparent throughout early development, offers neuroscientists a detailed view of its brain circuitry.

We won't all be loners after lockdown, but we will be anxious upon returning to our normal social lives. As we emerge from lockdown, we should be aware of this new sensitivity and anxiety, but recognise that overcoming it is necessary for returning to a normal, healthy, social existence.

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Materials provided by Sainsbury Wellcome Centre. Note: Content may be edited for style and length.

Journal Reference:

1. Hande Tunbak, Mireya Vazquez-Prada, Thomas Michael Ryan, Adam Raymond Kampff, Elena Dreosti. Whole-brain mapping of socially isolated zebrafish reveals that lonely fish are not loners. eLife, 2020; 9 DOI: 10.7554/eLife.55863