The gut-brain connection for social development
Summary: Healthy gut microbes promote 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 treatments for disorders associated with deficits in social behavior.
Source: University of Oregon
In order to learn to socialize, zebras must trust their gut.
Gut microbes prompt specialized cells to make extra connections in brain circuits that control social behavior, new UO research in zebrafish shows. Pruning is necessary 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 may be transferable between species – and may point 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 things that happen in larger, furry animals.”
The team reports their 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 required for one particular type of social interaction.
Normally, 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 show no interest.
Here, the team found a pathway that connects microbes in the gut to these neurons in the brain. In healthy fish, gut microbes prompted cells called microglia to sever extra connections between neurons.
Pruning is a normal part of healthy brain development. Like clutter on a counter, extra neural connections can get in the way of the ones that really matter, resulting in garbled messages.
In zebrafish without these gut microbes, pruning did not occur, and the fish showed a social deficit.
“We’ve known for some time that the microbiome affects many things during development,” Washbourne 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 that limit.”
In another paper, the team identified two defining characteristics of this set of social neurons that can be shared by mice and zebrafish. One is that these cells can be identified by the inclusion of similar genes – an indication that they may have similar roles in the brains of both species.
Such signatures can be used to identify neurons that serve this role in different brains. Another is that “neurons with the same gene signature in mice are in roughly the same brain locations as zebrafish social neurons,” Eisen said.
The finding strengthens the researchers’ belief that their zebrafish work could be translated to mice or humans. It’s easier to study the details of zebrafish brain development, 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 point for understanding other species.
Both gut microbiome disruption and poor pruning of neural synapses have been linked to a range of neuropsychiatric conditions such as autism spectrum disorder.
“If we can connect them, it could facilitate better therapy for a wide range of disorders,” said Joseph Bruckner, a postdoctoral fellow in the Eisen and Washbourne labs and first author on PLOS Biology paper. His next step is to discover which molecules link bacteria to microglia, mapping the pathway between microbes and behavior in even greater detail.
About this microbiome and social development research
Original Research: Open access.
“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 has been linked to neurodevelopmental conditions such as autism spectrum disorder. Recent work suggests that the microbiota modulates the behavioral phenotypes associated with these disorders.
We found that the zebrafish microbiota is required for normal social behavior and discovered a molecular pathway linking the microbiota, microglial remodeling of neuronal circuits, and social behavior in this experimentally tractable vertebrate model.
Examining the neural correlates of behavior, we found that the microbiota limits the neurite complexity and targeting of forebrain neurons required for normal social behavior and is essential for the localization of forebrain microglia, brain-based phagocytes that remodel neuronal arches.
The microbiota also influences microglial molecular functions, including promoting the expression of the complement signaling pathway and synaptic remodeling factors c1q. Several different bacterial taxa are individually sufficient for normal microglial and neuronal phenotypes, suggesting that host neuroimmune development is sensitive to a feature common among many bacteria.
Our results demonstrate that the microbiota influences zebrafish social behavior by stimulating microglial remodeling of forebrain circuits during early neurodevelopment and suggest avenues for novel interventions in multiple neurodevelopmental disorders.
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