Differential gene expression in the mesocorticolimbic system of innately high- and low-impulsive rats

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dc.contributor.author Moloney, Gerard M.
dc.contributor.author van Oeffelen, Wesley E. P. A.
dc.contributor.author Ryan, Feargal J.
dc.contributor.author van de Wouw, Marcel
dc.contributor.author Cowan, Caitlin S. M.
dc.contributor.author Claesson, Marcus J.
dc.contributor.author Schellekens, Harriët
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Cryan, John F.
dc.date.accessioned 2019-04-15T12:43:51Z
dc.date.available 2019-04-15T12:43:51Z
dc.date.issued 2019-02-06
dc.identifier.citation Moloney, G. M., van Oeffelen, W. E. P. A., Ryan, F. J., van de Wouw, M., Cowan, C., Claesson, M. J., Schellekens, H., Dinan, T. G. and Cryan, J. F. (2019) 'Differential gene expression in the mesocorticolimbic system of innately high- and low-impulsive rats', Behavioural Brain Research, 364, pp. 193-204. doi: 10.1016/j.bbr.2019.01.022 en
dc.identifier.volume 364 en
dc.identifier.startpage 193 en
dc.identifier.endpage 204 en
dc.identifier.issn 0166-4328
dc.identifier.uri http://hdl.handle.net/10468/7764
dc.identifier.doi 10.1016/j.bbr.2019.01.022 en
dc.description.abstract Impulsivity is an important component of many psychiatric illnesses and has been associated with a number of psychiatric disorders such as bipolar disorder and attention deficit / hyperactivity disorder (ADHD). Exploring the different aspects of impulsive behaviour and assigning these to specific neurobiological pathways would advance our interpretation of disorders for which impulsivity is key. Pharmacological studies have implicated a number of neurotransmitters in impulsivity, which in turn have been shown to be affected by several genes in both rodent and human studies of impulsivity. Here, we examine impulsivity-related differences in gene expression in finer detail, using the 2-choice serial reaction time task (2-CSRTT) to assess the molecular signature of impulsivity in brain regions previously linked to impulsive behaviour. Wistar rats were rated as high, (n = 6), intermediate, (n = 12) or low impulsive (n = 6), based on premature responses in the 2-CSRTT, after which RNA was extracted from the nucleus accumbens core (NAcc) and ventral prefrontal cortex (vPFC). RNA from the NAcc and vPFC of high and low impulsivity rats (n = 6 per group) was analysed for differential gene expression patterns and exon usage using RNA poly-A tail sequencing. Pnisr, Mal, and Tspan2 were significantly increased in the NAcc of highly impulsive rats, whereas Ube3a was significantly decreased. No differences were seen in the vPFC. In addition to changes in gene expression, Tspan2 displayed differential exon usage in impulsive rats, while functionally, gene expression changes were related to membrane depolarisation and changes in exon usage were linked to sphingolipid breakdown. The changes in gene expression and exon usage observed in this study represent an important step towards defining the molecular architecture of impulsivity. This study therefore represents an important starting point for analysis of the biological role of impulsivity in addiction and other neurological conditions associated with impulsive phenotypes. en
dc.description.sponsorship Higher Education Authority (Molecular Medicine Ireland (as part of the Clinical & Translational Research Scholars Programme under the Programme for Research in Third Level Institutions (PRTLI) Cycle 5 and co-funded under the European Regional Development Fund (ERDF)); Enterprise Ireland (Grant Numbers CC2008-001 and TC2013-000); en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S0166432818308714
dc.rights © 2019 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Impulsivity en
dc.subject Nucleus accumbens core en
dc.subject RNA-sequencing en
dc.subject Genomics en
dc.subject Ventral Prefrontal cortex en
dc.title Differential gene expression in the mesocorticolimbic system of innately high- and low-impulsive rats en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John F Cryan, Department Of Anatomy & Neuroscience, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.cryan@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 18 months after publication by request of the publisher. en
dc.check.date 2020-08-06
dc.date.updated 2019-04-15T12:30:39Z
dc.description.version Accepted Version en
dc.internal.rssid 481638252
dc.contributor.funder European Regional Development Fund en
dc.contributor.funder Enterprise Ireland en
dc.contributor.funder Higher Education Authority en
dc.contributor.funder Seventh Framework Programme en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Horizon 2020 en
dc.contributor.funder H2020 Marie Skłodowska-Curie Actions en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Behavioural Brain Research en
dc.internal.copyrightchecked No !!CORA!!
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.internal.IRISemailaddress caitlin.cowan@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/278948/EU/Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes/TACTICS en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/ en
dc.relation.project info:eu-repo/grantAgreement/EC/H2020::MSCA-IF-EF-ST/797592/EU/Gut microbiota-Microglia Interactions in NeuroDevelopment/GutMIND en
dc.identifier.eissn 1872-7549


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© 2019 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license Except where otherwise noted, this item's license is described as © 2019 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
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