Impulsive choices in mice lacking imprinted Nesp55

Dent, Claire, Humby, Trevor ORCID: https://orcid.org/0000-0002-1840-1799, Swaden Lewis, Katie J., Plagge, A, Fischer-Colbrie, R, Wilkins, J. F., Wilkinson, Lawrence ORCID: https://orcid.org/0000-0002-9337-6124 and Isles, Anthony Roger ORCID: https://orcid.org/0000-0002-7587-5712 2016. Impulsive choices in mice lacking imprinted Nesp55. Genes, Brain and Behavior 15 (8) , pp. 693-701. 10.1111/gbb.12316

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Abstract

Genomic imprinting is the process whereby germline epigenetic events lead to parent-of-origin specific monallelic expression of a number of key mammalian genes. The imprinted gene Nesp is expressed from the maternal allele only and encodes for Nesp55 protein. In the brain, Nesp55 is found predominately in discrete areas of the hypothalamus and midbrain. Previously, we have shown that loss of Nesp55 gives rise to alterations in novelty-related behaviour. Here, we extend these findings and demonstrate, using the Nespm/+ mouse model, that loss of Nesp55 leads to impulsive choices as measured by a delayed-reinforcement task, whereby Nespm/+ mice were less willing to wait for a delayed, larger reward, preferring instead to choose an immediate, smaller reward. These effects were highly specific as performance in another component of impulsive behaviour, the ability to stop a response once started as assayed in the stop-signal reaction time task, was equivalent to controls. We also showed changes in the serotonin system, a key neurotransmitter pathway mediating impulsive behaviour. First, we demonstrated that Nesp55 is co-localized with serotonin and then went on to show that in midbrain regions there were reductions in mRNA expression of the serotonin-specific genes Tph2 and Slc6a4, but not the dopamine-specific gene Th in Nespm/+ mice; suggesting an altered serotonergic system could contribute, in part, to the changes in impulsive behaviour. These data provide a novel mode of action for genomic imprinting in the brain and may have implications for pathological conditions characterized by maladaptive response control

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI) Psychology
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Action impulsivity; choice impulsivity; delayed reinforcement; epigenetics; genomic imprinting; imprinted genes; mouse; Nesp55; serotonin; stop-signal reaction; time
Additional Information:	PDF uploaded in accordance with publisher's policies at http://www.sherpa.ac.uk/romeo/issn/1601-1848/ (accessed 26.8.16).
Publisher:	Wiley-Blackwell
ISSN:	1601-1848
Date of First Compliant Deposit:	24 August 2016
Date of Acceptance:	6 August 2016
Last Modified:	08 Nov 2023 09:52
URI:	https://orca.cardiff.ac.uk/id/eprint/94008

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