Deletion of alpha-synuclein decreases impulsivity in mice

Peña-Oliver, Y, Buchman, V L, Dalley, J W, Robbins, T W, Schumann, G, Ripley, Tamzin, King, S L and Stephens, D N (2012) Deletion of alpha-synuclein decreases impulsivity in mice. Genes, Brain and Behavior, 11 (2). pp. 137-146. ISSN 1601-1848

[img] PDF
Restricted to SRO admin only

Download (732kB)

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.

Item Type: Article
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology > BF0608 Will. Volition. Choice. Control
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
Depositing User: Library Cataloguing
Date Deposited: 28 May 2012 08:01
Last Modified: 01 Apr 2017 08:57
URI: http://sro.sussex.ac.uk/id/eprint/39439

View download statistics for this item

📧 Request an update