Stilling, RM;Moloney, GM;Ryan, FJ;Hoban, AE;Bastiaanssen, TFS;Shanahan, F;Clarke, G;Claesson, MJ;Dinan, TG;Cryan, JF

2018

May

Elife

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

Validated

WOS: 54 ()

AUTISM SPECTRUM DISORDERS ANXIETY-LIKE BEHAVIOR GUT-BRAIN AXIS POSTMYOCARDIAL INFARCTION DEPRESSION SET ENRICHMENT ANALYSIS CENTRAL-NERVOUS-SYSTEM LARGE GENE LISTS GERM-FREE MICE INTESTINAL MICROBIOTA NEURAL CIRCUITS

7

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).

CAMBRIDGE

2050-084X

10.7554/eLife.33070