A gut-brain connection for social development

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

Source: University of Oregon

To learn to socialize, zebrafish must trust their instincts.

Gut microbes encourage specialized cells to prune extra connections in brain circuitry that control social behavior, according to new UO research in zebrafish. Pruning is essential for the development of normal social behavior.

The researchers also found that these “social” neurons are similar in zebrafish and mice. This suggests that the findings could translate across species and could potentially pave the way to treatments for a range 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 what is happening in larger furry animals.”

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

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

Normally, if two zebrafish see each other through a glass partition, they will approach and swim side by side. But the zebrafish without these neurons shows no interest.

Here, the team discovered a pathway linking gut microbes to these brain neurons. In healthy fish, gut microbes prompted cells called microglia to carve out extra connections between neurons.

Pruning is a normal part of healthy brain development. Like the clutter on a counter, extra neural connections can get in the way of the ones that really matter, resulting in confusing messages.

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

“We’ve known for some time that the microbiome influences a lot of things during development,” Washbourne said. “But there hasn’t been a lot of hard data on how the microbiome influences the brain. We did a lot to push the boundaries 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. The first is that these cells could be identified by turning on similar genes, a clue that they might play similar roles in the brains of both species.

It shows a brain
Here, the team discovered a pathway linking gut microbes to these brain neurons. Image is in public domain

Such signature signs could be used to identify neurons that play this role in different brains. The other is that “neurons with the same genetic signature in mice are found in roughly the same brain locations as social neurons in zebrafish,” Eisen said.

This finding reinforces the researchers’ belief that their work on zebrafish could translate to mice or humans. It’s easier to study the workings of brain development in zebrafish, where scientists can observe the formation of neural circuits through the transparent bodies of young fish. Researchers could then take the knowledge of the zebrafish and use it as a starting point for understanding other species.

Disruption of the gut microbiome and improperly sized neural synapses have been linked to a range of neuropsychiatric disorders like autism spectrum disorders.

“If we can link them together, it could facilitate better therapies for a wide range of disorders,” said Joseph Bruckner, postdoctoral fellow at Eisen and Washbourne Laboratories and first author on the PLOS Biology paper. His next step is to determine which molecules link bacteria to microglia, mapping the pathway between microbes and behavior in even greater detail.

See also

This shows 5 zebra finches in a cage

About this microbiome and social development research news

Author: Press office
Source: University of Oregon
Contact: Press Office – University of Oregon
Image: Image is in public domain

Original research: Free access.
“The microbiota promotes social behavior by modulating microglial remodeling of forebrain neurons” by Judith Eisen et al. PLOS Biology


Microbiota promotes social behavior by modulating microglial remodeling of forebrain neurons

Host-associated microbiota guide the trajectory of developmental programs, and altered microbiota composition is linked to neurodevelopmental conditions such as autism spectrum disorders. Recent work suggests that microbiota modulate the behavioral phenotypes associated with these disorders.

We discovered that the zebrafish microbiota is necessary for normal social behavior and revealed a molecular pathway linking the microbiota, microglial remodeling of neural circuits and social behavior in this experimental model vertebrate.

By examining the neural correlates of behavior, we found that the microbiota limits neurite complexity and targeting of forebrain neurons necessary for normal social behavior and is required for localization of forebrain microglia, brain resident phagocytes that reshape neural arbours.

The microbiota also influences microglial molecular functions, in particular by promoting the expression of the complement signaling pathway and synaptic remodeling factor. c1q. Several distinct bacterial taxa are individually sufficient for normal microglial and neuronal phenotypes, suggesting that host neuroimmune development is sensitive to a feature common to many bacteria.

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

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