The microbiome regulates amygdala-dependent fear recall

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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.date.accessioned 2018-06-15T11:47:17Z
dc.date.available 2018-06-15T11:47:17Z
dc.date.issued 2018
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.volume 23
dc.identifier.issued 5
dc.identifier.startpage 1134
dc.identifier.endpage 1144
dc.identifier.issn 1359-4184
dc.identifier.uri http://hdl.handle.net/10468/6347
dc.identifier.doi 10.1038/mp.2017.100
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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Nature Publishing Group en
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
dc.internal.authorcontactother Gerard Clarke, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. +353-21-490-3000 E-mail: g.clarke@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
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.description.status Peer reviewed
dc.identifier.journaltitle Molecular Psychiatry en
dc.internal.IRISemailaddress g.clarke@ucc.ie; j.cryan@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/


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© 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/ Except where otherwise noted, this item's license is described as © 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/
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