Five choice serial reaction time performance in the HdhQ92 mouse model of Huntington's disease

Abstract

Huntington's disease is an autosomal dominant genetic disorder, with motor, cognitive and psychiatric symptoms. To date there is no cure. In order to understand better this disease and to develop novel treatments, many genetically modified animal models of Huntington's disease have been created. However, to utilize these models fully, appropriate functional assays need to be developed for behavioural assessments of the mice. Various facets of attention have been reported to be affected in Huntington's disease patients, and the Hdh(Q92/Q92) mice have been shown to have deficits on operant tasks which have attentional components. In the present study, the Hdh(Q92/Q92) mouse model is assessed on a well established test of attentional function, the operant 5-choice serial reaction time task (5-CSRT), in which the mice must respond with a nose poke to light stimuli presented randomly across a 5 hole light array to receive a reward. In the present paper, the Hdh(Q92/Q92) mice exhibited deficits on the 5-CSRT when pseudorandomly presented with stimuli of different durations. However, alterations in the pacing of the task, therefore requiring an increase in sustained attention, did not affect the Hdh(Q92/Q92) mice more than their wildtype littermates. This study indicates that the Hdh(Q92/Q92) mice may have deficits in aspects of attentional function, in particular disruption in the ability to maintain attention in the visuospatial domain, suggesting that this knock-in mouse model of Huntington's disease may be a relevant model of the disease for the testing of novel therapeutic interventions.