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 F.S. Bastiaanssen, Fergus Shanahan, Gerard Clarke, Marcus J. Claesson, Timothy G. Dinan, John F. Cryan

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

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).

Original languageEnglish
Article numbere33070
Number of pages21
JournaleLife
Volume7
DOIs
Publication statusPublished - 29 May 2018
Externally publishedYes

Keywords

  • RNA splicing
  • amygdala
  • microbiome-deficient mice
  • social behaviour
  • microbiota
  • Germ-free

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