The microbiome regulates amygdala-dependent fear recall

Hoban, Alan E.; Stilling, Roman M.; Moloney, Gerard M.; Shanahan, Fergus; Dinan, Timothy G.; Clarke, Gerard; Cryan, John F.

The microbiome regulates amygdala-dependent fear recall

dc.contributor.author	Hoban, Alan E.
dc.contributor.author	Stilling, Roman M.
dc.contributor.author	Moloney, Gerard M.
dc.contributor.author	Shanahan, Fergus
dc.contributor.author	Dinan, Timothy G.
dc.contributor.author	Clarke, Gerard
dc.contributor.author	Cryan, John F.
dc.contributor.funder	Science Foundation Ireland
dc.contributor.funder	Irish Research Council
dc.contributor.funder	Brain and Behavior Research Foundation
dc.contributor.funder	Health Research Board
dc.contributor.funder	Department of Agriculture, Food and the Marine
dc.contributor.funder	Enterprise Ireland
dc.date.accessioned	2018-06-15T11:47:17Z
dc.date.available	2018-06-15T11:47:17Z
dc.date.issued	2018
dc.description.abstract	The amygdala is a key brain region that is critically involved in the processing and expression of anxiety and fear-related signals. In parallel, a growing number of preclinical and human studies have implicated the microbiome-gut-brain in regulating anxiety and stress-related responses. However, the role of the microbiome in fear-related behaviours is unclear. To this end we investigated the importance of the host microbiome on amygdala-dependent behavioural readouts using the cued fear conditioning paradigm. We also assessed changes in neuronal transcription and post-transcriptional regulation in the amygdala of naive and stimulated germfree (GF) mice, using a genome-wide transcriptome profiling approach. Our results reveal that GF mice display reduced freezing during the cued memory retention test. Moreover, we demonstrate that under baseline conditions, GF mice display altered transcriptional profile with a marked increase in immediate-early genes (for example, Fos, Egr2, Fosb, Arc) as well as genes implicated in neural activity, synaptic transmission and nervous system development. We also found a predicted interaction between mRNA and specific microRNAs that are differentially regulated in GF mice. Interestingly, colonized GF mice (ex-GF) were behaviourally comparable to conventionally raised (CON) mice. Together, our data demonstrates a unique transcriptional response in GF animals, likely because of already elevated levels of immediate-early gene expression and the potentially underlying neuronal hyperactivity that in turn primes the amygdala for a different transcriptional response. Thus, we demonstrate for what is to our knowledge the first time that the presence of the host microbiome is crucial for the appropriate behavioural response during amygdala-dependent memory retention.	en
dc.description.sponsorship	Irish Research Council (Government of Ireland Postdoctoral Fellowship (GOIPD/2014/355); Brain and Behavior Research Foundation (20771)	en
dc.description.status	Peer reviewed
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Hoban, A. E., Stilling, R. M., Moloney, G., Shanahan, F., Dinan, T. G., Clarke, G. and Cryan, J. F. (2017) 'The microbiome regulates amygdala-dependent fear recall', Molecular Psychiatry, 23, pp. 1134–1144. doi: 10.1038/mp.2017.100	en
dc.identifier.doi	10.1038/mp.2017.100
dc.identifier.endpage	1144
dc.identifier.issn	1359-4184
dc.identifier.issued	5
dc.identifier.journaltitle	Molecular Psychiatry	en
dc.identifier.startpage	1134
dc.identifier.uri	https://hdl.handle.net/10468/6347
dc.identifier.volume	23
dc.language.iso	en	en
dc.publisher	Nature Publishing Group	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/
dc.relation.uri	https://www.nature.com/articles/mp2017100
dc.rights	© 2018, the Authors. This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the licenseholder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject	Neuronal circuits	en
dc.subject	Stress-response	en
dc.subject	Brain	en
dc.subject	Anxiety	en
dc.subject	Memory	en
dc.subject	Microrna	en
dc.subject	Mice	en
dc.subject	Expression	en
dc.subject	Disorders	en
dc.subject	Behavior	en
dc.title	The microbiome regulates amygdala-dependent fear recall	en
dc.type	Article (peer-reviewed)	en