New zebrafish research from the University of Oregon demonstrates that gut bacteria urge specialized cells to prune out excess connections in brain circuits that drive social behavior. Pruning is an important part of learning how to act normally in social situations.

These ‘social’ neurons were also shown to be similar between zebrafish and mice. This means that the results might apply to other species and may also hint at potential treatments for a variety of neurodevelopmental problems.

“This is a big step forward,” says co-lead author and UO neuroscientist Judith Eisen. “It also sheds light on things that are going on in larger, furrier animals.”  

The team’s findings are reported in two new articles in PLOS Biology and BMC Genomics.

Even though social behavior is complicated and involves many parts of the brain, Washbourne’s lab has already found a group of neurons in the zebrafish brain that are needed for one type of social interaction. When two zebrafish view one other through a glass barrier, they usually swim alongside one another. However, zebrafish lacking these neurons don’t exhibit any interest.

Here, the team discovered a connection between these brain cells and microorganisms in the digestive tract. Microbes in the digestive tract of healthy fish prompted a kind of cell called microglia to eliminate unnecessary connections between neurons.

Pruning is a typical process in the growth of a healthy brain. Like clutter on a counter, excess brain connections can obstruct the ones that are most important, causing information to get jumbled.

When these gut microbes were taken away from zebrafish, the pruning didn’t happen, and the fish had trouble getting along with other fish.

“We’ve known for a while that the microbiome influences a lot of things during development,” Washbourne adds. “But there hasn’t been a lot of concrete data about how the microbiome is influencing the brain. We’ve done quite a bit to push the boundary there.”

In a second piece of work, the team found two characteristics of this group of social neurons that mice and zebrafish may share. One is that these cells could be recognized because they have similar genes turned on, which is a sign that they might have functions that are similar in both species’ brains. Neurons that perform this function may have unique signatures that can be utilized to locate them across brains. The second is that, according to Eisen, “neurons with the same gene signature in mice are in approximately the same brain locations as the zebrafish social neurons.”

The researchers are now more confident that their findings in zebrafish could apply to mice or humans. Zebrafish are an excellent model for studying the specifics of brain development because their transparent bodies allow researchers to observe the formation of neuronal connections. The knowledge gained from studying zebrafish could subsequently be applied to understanding other species.

Disruption of the gut microbiome, as well as improper pruning of neuronal synapses, have been associated with several neuropsychiatric disorders, including autism spectrum disorder.

“If we can tie these together, it might facilitate better therapeutics for a wide range of disorders,” adds first author Joseph Bruckner.  His next step is to figure out what molecules connect the bacteria to the microglia. This will help him make a more detailed map of the path between microbes and behavior.

Image Credit: Sebastian Gollnow/picture alliance via Getty Images

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