Neuroscientists Hack the Brain's Circuitry for Winning and Losing

Nature's already figured out if you're going to win that fight or not, at least if you're a zebrafish.

We may be programmed in such ways as to predispose us toward "winning" or "losing," according to research published this week in Science by neuroscientists at the RIKEN Brain Science Institute in Japan. This is the case, at least, for zebrafish, which were found to have separate neural circuits whose relative activity could be used to predict the outcome of fights. Generally, what they've found is a biological mechanism for conflict resolution and social aggression.

The neural subregions in question are both part of the dorsal habenula (dHb), a wad of neurons right in the brain's central nut responsible for such things as stress and pain responses, reproductive behavior, and learning.

"Losing" zebrafish were found to have increased neural activity in the lateral regions of the dHb—particularly a pathway linking it to another brain region called the interpeduncular nucleus (IPN)—while "winning" fish were found to have increased activity in the medial regions of the dHb.

Moreover, by selectively silencing these regions, the researchers were able to essentially hard-wire different fish for winning and losing. Which is a bit weird.

"Aggression is an evolutionarily conserved behavior critical for animal survival," the authors explain. "When conflict is unavoidable, animals use aggression to establish a social hierarchy that determines how to share limited resources. Most animal conflicts aim at establishing a social hierarchy rather than causing lethal damage to opponents, which achieves the best cost-benefit for the group. However, the biological mechanisms governing the resolution of social conflict remain largely unknown."

And how better then to shed some light on this mystery than staging some actual zebrafish fights. This common model organism also happens to feature a chip on its shoulder, and, indeed, recent years have seen intense research interest in zebrafish brawling behaviors.

The zebrafish fights staged by the RIKEN neuroscientists went something like this. First, pairs of male fish were separated for 24 hour periods. Then, they were, well, dropped into the same tank. There's not a whole lot to the actually getting them to fight part, as it turns out.

"Dyadic male zebrafish fights proceed in a stereotypic manner, starting with each animal exhibiting display behaviors, followed by circling and biting attacks, and ending when one fish shows fleeing behavior indicating surrender," the paper explains.

What's interesting about zebrafish brawling is that it doesn't just keep happening every time a couple of males are in proximity to one another. This is a feature of the fish community's social hierarchy. Once some initial fights go down, it becomes established who the tough-guy fish are in the group—which are the ones that will go on to have the best reproductive opportunities—and all of the other fish respect that and something like harmony is achieved. Makes sense.

The RIKEN group got their fish-fight neural close-ups in two different ways. First, researchers looked at brain slices of zebrafish post-fight and produced records of neural activity using calcium imaging. Next, they used implanted electrodes to monitor this activity in real-time as the zebrafish actually did their thing. This is how the varying levels of activity in the fish's dHbs were observed.

The final task was to actually manipulate these neural regions to see if the zebrafish could be made to be more or less aggressive, which was accomplished using transgenic fish, e.g. genetically modified fish. This worked about as expected, adding further evidence to the idea that the dHb-IPN pathway acts as a sort of neural switch for fight-winning.

There is still much work to be done. For one thing, the current study looks at these brain regions in relative isolation, while it may well be the case that the "winning" predisposition involves many interacting circuits. As an accompanying Science Perspective explains, "The next step will be to combine wholebrain imaging, optogenetic manipulations, and CRISPR-mediated genome editing to unravel the complete circuits underlying social behaviors in vertebrates."