PUBLICATION

The microbiota promotes social behavior by modulating microglial remodeling of forebrain neurons

Authors
Bruckner, J.J., Stednitz, S.J., Grice, M.Z., Zaidan, D., Massaquoi, M.S., Larsch, J., Tallafuss, A., Guillemin, K., Washbourne, P., Eisen, J.S.
ID
ZDB-PUB-221102-7
Date
2022
Source
PLoS Biology   20: e3001838 (Journal)
Registered Authors
Eisen, Judith S., Guillemin, Karen, Larsch, Johannes, Tallafuss, Alexandra, Washbourne, Philip
Keywords
none
MeSH Terms
  • Animals
  • Autism Spectrum Disorder*/metabolism
  • Microbiota*
  • Microglia/metabolism
  • Neurons/physiology
  • Prosencephalon
  • Social Behavior
  • Zebrafish
PubMed
36318534 Full text @ PLoS Biol.
Abstract
Host-associated microbiotas guide the trajectory of developmental programs, and altered microbiota composition is linked to neurodevelopmental conditions such as autism spectrum disorder. Recent work suggests that microbiotas modulate behavioral phenotypes associated with these disorders. We discovered that the zebrafish microbiota is required for normal social behavior and reveal a molecular pathway linking the microbiota, microglial remodeling of neural circuits, and social behavior in this experimentally tractable model vertebrate. Examining neuronal correlates of behavior, we found that the microbiota restrains neurite complexity and targeting of forebrain neurons required for normal social behavior and is necessary for localization of forebrain microglia, brain-resident phagocytes that remodel neuronal arbors. The microbiota also influences microglial molecular functions, including promoting expression of the complement signaling pathway and the 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 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 pathways for new interventions in multiple neurodevelopmental disorders.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping