title: Impulsive choices in mice lacking imprinted Nesp55.
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.
authors: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute.
authors: C L
authors: CL
authors: Dent
authors: Behavioural Genetics Group, School of Psychology, Cardiff University, Cardiff, UK.
authors: T
authors: T
authors: Humby
authors: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute.
authors: K
authors: K
authors: Lewis
authors: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: A
authors: A
authors: Plagge
authors: Department of Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: R
authors: R
authors: Fischer-Colbrie
authors: Ronin Institute, Montclair, NJ, USA.
authors: J F
authors: JF
authors: Wilkins
authors: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute.|Behavioural Genetics Group, School of Psychology, Cardiff University, Cardiff, UK.
authors: L S
authors: LS
authors: Wilkinson
authors: Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute.
authors: A R
authors: AR
authors: Isles
mesh_terms: D000483:Alleles; D000818:Animals; D002755:Choice Behavior / Q000502:physiology; D002864:Chromogranins / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004298:Dopamine / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D018392:Genomic Imprinting; D007175:Impulsive Behavior / Q000502:physiology*; D008297:Male; D000072741:Maternal Inheritance; D051379:Mice; D008810:Mice, Inbred C57BL; D012054:Reinforcement, Psychology; D012701:Serotonin / Q000235:genetics / Q000378:metabolism
chemical_list: D002864:Chromogranins; D012701:Serotonin; C498642:Gnas protein, mouse; D019205:GTP-Binding Protein alpha Subunits, Gs; D004298:Dopamine
keywords: Action impulsivity; Nesp55; choice impulsivity; delayed reinforcement; epigenetics; genomic imprinting; imprinted genes; mouse; serotonin; stop-signal reaction; time