Summary: Healthy gut microbes encourage synaptic pruning in brain circuits associated with social behavior. Previous research has linked both poor synaptic pruning and gut health to neurodevelopmental disorders including ASD. The new findings could pave the way for the treatment of disorders associated with social behavioral deficits.

source: University of Oregon

To learn to socialize, zebrafish need to trust their gut.

A new study in zebrafish shows that gut microbes encourage specialized cells to prune extra connections in brain circuits that control social behavior. Pruning is necessary for the development of normal social behaviour.

The researchers also found that these “social” neurons are similar in zebrafish and mice. This suggests that the findings may translate between species — and could point the way to treatments for a range of neurodevelopmental conditions.

“This is a huge step forward,” said neuroscientist Judith Eisen, who led the work with neuroscientist Philip Washburn. “It also sheds light on the things that happen in larger, furry animals.”

The team is publishing their findings in two new papers published in Biology Plus And the BMC genomics.

While social behavior is a complex phenomenon involving many parts of the brain, Washburn’s lab previously identified a set of neurons in the zebrafish brain that are required for a specific type of social interaction.

Usually, if two zebrafish see each other through a glass partition, they will approach each other and swim side by side. But zebrafish without these neurons doesn’t show any interest.

Here, the team found a pathway that connects gut microbes to these neurons in the brain. In healthy fish, gut microbes stimulated cells called microglia to prune extra connections between neurons.

Pruning is a normal part of healthy brain development. Like clutter on the counter, additional neural connections can get in the way of that really important task, resulting in garbled messages.

In zebrafish without gut microbes, pruning did not occur, and the fish showed social deficits.

“We’ve known for a while that the microbiome affects a lot of things during evolution,” Washburn said. But there hasn’t been a lot of concrete data on how the microbiome affects the brain. We’ve done a lot to push the boundaries there.”

In a second paper, the team identified two specific features of this group of social neurons that mice and zebrafish can share. One is that these cells can be recognized by turning on similar genes – evidence that they may play similar roles in the brains of both species.

This indicates a brain
Here, the team found a pathway that connects gut microbes to these neurons in the brain. The image is in the public domain

These signature tags can be used to identify which neurons perform this role in different brains. The other is that “neurons with the same genetic signature in mice are located in roughly the same brain sites as the social neurons of zebrafish,” Eisen said.

This finding reinforces the researchers’ belief that their work in zebrafish can translate to mice or humans. It is easier to study the nuts and bolts of brain development in zebrafish, as scientists can watch neural circuits form through the transparent bodies of young fish. The researchers can then take the insights from the zebrafish and use them as a starting point for understanding other species.

Disruption of the gut microbiome and impaired synapse pruning have both been linked to a range of neuropsychiatric conditions such as autism spectrum disorder.

Joseph Bruckner, a postdoctoral researcher at Eisen and Washburn Laboratories and first author on Biology Plus paper. His next step is to discover the molecules that bind bacteria to microglia, and to map the pathway between microbes and behavior in more detail.

see also

This shows 5 zebra birds in a cage

About this microbiome and social development research news

author: press office
source: University of Oregon
Contact: Press Office – University of Oregon
picture: The image is in the public domain

original search: open access.
“Probiotics enhance social behavior by modulating microglia remodeling of forebrain neurons” by Judith Eisen et al. Biology Plus


Microorganisms enhance social behavior by modulating microglia remodeling of forebrain neurons

Host-associated microbes direct the course of developmental programs, and altered microbiota composition is associated with neurodevelopmental conditions such as autism spectrum disorder. Recent work indicates that microbiota modulate behavioral phenotypes associated with these disorders.

We discovered that zebrafish microbiota is required for normal social behavior and reveals a molecular pathway that links the microbiota and the microcellular remodeling of neural circuits and social behavior in this experimental vertebrate model.

Examining the neural correlates of behavior, we found that the microorganisms restrict neurite complexity and target forebrain neurons that are required for normal social behavior and are essential for the localization of forebrain microglia, brain-resident macrophages that remodel neural thrones.

Microorganisms also influence microglia molecular functions, including enhancing expression of the complement signaling pathway and synaptic remodeling factor. c1q. Several distinct bacterial taxa are individually sufficient for the phenotypes of microglia and neurons, suggesting that host neuronal development is sensitive to a feature common to many bacteria.

Our results demonstrate that the microbiota influences social behavior of zebrafish by stimulating microglial remodeling of forebrain circuits during early neurodevelopment and suggest pathways for novel interventions in multiple neurodevelopmental disorders.

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