eLife (May 2018)

Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice

  • Roman M Stilling,
  • Gerard M Moloney,
  • Feargal J Ryan,
  • Alan E Hoban,
  • Thomaz FS Bastiaanssen,
  • Fergus Shanahan,
  • Gerard Clarke,
  • Marcus J Claesson,
  • Timothy G Dinan,
  • John F Cryan

DOI
https://doi.org/10.7554/eLife.33070
Journal volume & issue
Vol. 7

Abstract

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Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction. In GF mice the dynamic response seen in controls was attenuated and replaced by a marked increase in expression of splicing factors and alternative exon usage in GF mice upon stimulation, which was even more pronounced in exGF mice. In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions. Our findings may help toward understanding neurodevelopmental events leading to social behaviour dysregulation, such as those found in autism spectrum disorders (ASDs).

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