title: Deletion of alpha-synuclein decreases impulsivity in mice.
abstract: The presynaptic protein alpha-synuclein, associated with Parkinson's Disease (PD), plays a role in dopaminergic neurotransmission and is implicated in impulse control disorders (ICDs) such as drug addiction. In this study we investigated a potential causal relationship between alpha-synuclein and impulsivity, by evaluating differences in motor impulsivity in the 5-choice serial reaction time task (5-CSRTT) in strains of mice that differ in the expression of the alpha-synuclein gene. C57BL/6JOlaHsd mice differ from their C57BL/6J ancestors in possessing a chromosomal deletion resulting in the loss of two genes, snca, encoding alpha-synuclein, and mmrn1, encoding multimerin-1. C57BL/6J mice displayed higher impulsivity (more premature responding) than C57BL/6JOlaHsd mice when the pre-stimulus waiting interval was increased in the 5-CSRTT. In order to ensure that the reduced impulsivity was indeed related to snca, and not adjacent gene deletion, wild type (WT) and mice with targeted deletion of alpha-synuclein (KO) were tested in the 5-CSRTT. Similarly, WT mice were more impulsive than mice with targeted deletion of alpha-synuclein. Interrogation of our ongoing analysis of impulsivity in BXD recombinant inbred mouse lines revealed an association of impulsive responding with levels of alpha-synuclein expression in hippocampus. Expression of beta- and gamma-synuclein, members of the synuclein family that may substitute for alpha-synuclein following its deletion, revealed no differential compensations among the mouse strains. These findings suggest that alpha-synuclein may contribute to impulsivity and potentially, to ICDs which arise in some PD patients treated with dopaminergic medication.
authors.affiliation: School of Psychology, University of Sussex, Falmer, Brighton, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Peña-Oliver
authors.forename: V L
authors.initials: VL
authors.lastname: Buchman
authors.forename: J W
authors.initials: JW
authors.lastname: Dalley
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
authors.forename: G
authors.initials: G
authors.lastname: Schumann
authors.forename: T L
authors.initials: TL
authors.lastname: Ripley
authors.forename: S L
authors.initials: SL
authors.lastname: King
authors.forename: D N
authors.initials: DN
authors.lastname: Stephens
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003657:Decision Making / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D007175:Impulsive Behavior / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011930:Reaction Time / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism; D051845:gamma-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D051845:gamma-Synuclein