Researchers find gut-brain connection for social development

According to recent University of Oregon zebrafish research, gut microbes encourage specialized cells to remove extra connections from brain circuits that regulate social behaviour. Normal social behaviour cannot be developed without pruning.

Additionally, the researchers discovered that mice and zebrafish have similar "social" neurons. This suggests that the results might apply to other species and may also point to potential treatments for a variety of neurodevelopmental conditions.

"This is a big step forward," said UO neuroscientist Judith Eisen, who co-led the work with neuroscientist Philip Washbourne. "It also sheds light on things that are going on in larger, furrier animals."

The team reports their findings in two new papers, published in PLOS Biology and BMC Genomics.

Washbourne's lab has previously discovered a group of neurons in the zebrafish brain that is necessary for a specific type of social interaction, despite the fact that social behaviour is a complex phenomenon involving many different parts of the brain. Two zebrafish will typically approach and swim side by side if they can see each other through a glass wall. However, zebrafish lacking these neurons don't exhibit any interest.

Here, the team discovered a pathway connecting gut microbes to these brain neurons. Gut microbes encouraged microglia, a type of cell, to cut back on extra connections between neurons in healthy fish.

Pruning is a normal component of the development of a healthy brain. Extraneous neural connections, like clutter on a counter, can obstruct important ones, resulting in jumbled messages.

"We've known for a while that the microbiome influences a lot of things during development," Washbourne said. "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 paper, the team identified two defining features of this set of social neurons that may be shared by mice and zebrafish. One is that these cells could be identified by having similar genes turned on--a clue that they might serve similar roles in the brains of both species. Such signature signs could be used to identify neurons that serve this role in different brains. The other is that "neurons with the same gene signature in mice are in approximately the same brain locations as the zebrafish social neurons," Eisen said.

That finding strengthens the researchers' belief that their work in zebrafish could translate to mice or humans. It's easier to study the nuts and bolts of brain development in zebrafish, where scientists can watch neural circuits form through the young fish's transparent bodies. Researchers could then take the insights from zebrafish and use them as a starting place for understanding other species.

Both gut microbiome disruption and poor neural synapse pruning have been linked to a range of neuropsychiatric conditions like autism spectrum disorder.

"If we can tie these together, it might facilitate better therapeutics for a wide range of disorders," said Joseph Bruckner, a postdoc in the Eisen and Washbourne labs and the first author of the PLOS Biology paper. His next step is figuring out what molecules are linking the bacteria to the microglia, mapping the pathway between microbes and behaviour in even more detail. (ANI)