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Elife. 2018 May 29;7. pii: e33070. doi: 10.7554/eLife.33070.

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

Author information

1
APC Microbiome Institute, University College Cork, Cork, Ireland.
2
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
3
School of Microbiology, University College Cork, Cork, Ireland.
4
Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.

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).

KEYWORDS:

Social behaviour; activity-dependent transcription; amygdala; autism; microbiome; mouse; neurodevelopment; neuroscience

Conflict of interest statement

RS, GM, FR, AH, TB No competing interests declared, FS principal investigator in the APC Microbiome Institute, University College Cork, GC faculty member or funded investigator of the APC Microbiome Institute. The APC Microbiome Institute has conducted research funded by Pfizer, GlaxoSmithKline, Proctor & Gamble, Mead Johnson, Suntory Wellness, and Cremo, MC Marcus J Claesson: faculty member or funded investigator of the APC Microbiome Institute. The APC Microbiome Institute has conducted research funded by Pfizer, GlaxoSmithKline, Proctor & Gamble, Mead Johnson, Suntory Wellness, and Cremo, TD principal investigator in the APC Microbiome Institute, University College Cork. Has been an invited speaker at meetings organized by Servier, Lundbeck, Janssen, and AstraZeneca. JC principal investigator in the APC Microbiome Institute, University College Cork. Has been an invited speaker at meetings organized by Mead Johnson, Yakult, Alkermes, and Janssen.

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