The operant serial implicit learning task reveals early onset motor learning deficits in the Hdh knock-in mouse model of Huntington's disease.

Full Abstract

A range of genetic mouse models of Huntington's disease have been created. However, as knock-in models typically have milder phenotypes, they have frequently been overlooked as therapeutic tools in favour of the transgenic models that display severe behavioural symptoms. More sensitive tests are therefore required to reveal abnormalities and release the potential of knock-in lines. An implicit learning task for mice has been developed in the nine-hole operant box test apparatus, in which mice must respond to a sequence of lights in order to earn a reward. A light stimulus was presented randomly in one of five holes, to which a nose poke response resulted in the light being extinguished and a second light illuminated in a different hole. Response to the second light resulted in a liquid reward. To probe implicit learning, a predictable stimulus sequence was embedded among many unpredictable sequences. In the current study, the Hdh(Q92) mouse model of Huntington's disease was examined. At 4 months of age, Hdh(Q92/Q92) mice demonstrated clear and significant deficits in both accuracy and reaction time on all trials of the implicit learning task, with improved performance on predictable trials. We believe this to be the earliest reported behavioural deficit in the Hdh(Q92) knock-in mouse line. The results of this study validate the serial implicit learning task as a sensitive tool for the examination of implicit and motor learning deficits in mutant mice, and may provide a powerful test for probing potential treatments for Huntington's disease.

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Author information

Author/s: Trueman, Rebecca C (RC); Brooks, Simon P (SP); Jones, Lesley (L); Dunnett, Stephen B (SB);

Affiliation: School of Biosciences, Cardiff University, Museum Avenue, Cardiff, Wales, UK. truemanrc(-atsign-)cardiff.ac.uk

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The European journal of neuroscience (Eur J Neurosci), published in France. (Language: eng)

Reference: 2007-Jan; vol 25 (issue 2) : pp 551-8

Dates: Created 2007/02/07; Completed 2007/04/05;

PMID: 17284197, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Analysis of Variance
Animals
Behavior, Animal
Behavioral Symptoms - etiology; genetics
Conditioning, Operant - physiology
Disease Models, Animal
Female
Huntington Disease - complications; genetics; metabolism
Learning Disorders - etiology; genetics

Male
Mice
Mice, Transgenic
Nerve Tissue Proteins - genetics; metabolism
Neuropsychological Tests
Nuclear Proteins - genetics; metabolism
Reaction Time - genetics
Rotarod Performance Test - methods
Task Performance and Analysis

Associated Chemicals: Hdh protein, mouse (0) ; Huntington protein, mouse (0) ; Nerve Tissue Proteins (0) ; Nuclear Proteins (0)

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