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N. PATERSON, B. ALOSIO, S. RAMBOZ, L.C. PARK, D. HOWLAND, D. BURNNER

Background: Huntington’s Disease (HD) is a neurodegenerative illness that is characterized not only by severe motor deficits but also by early cognitive deficits that significantly increase the burden of the disease for patients and caregivers. Considerable efforts have been made, therefore, toward the assessment of putative cognitive impairments in HD mouse models.

Objectives: The present studies aimed to profile the zQ175 mouse model of HD in acquisition, reversal and intradimensional shift in a simple visual discrimination task. Methods: Two independent cohorts of zQ175 mice at approximately 6 and 12 months old were assessed in an operant touchscreen assay. Following an initial period of instrumental training, WT and zQ175 HD mice were tested for their ability to discriminate two complex visual stimuli (Discrimination phase). Following this discrimination phase, the reinforcement contingencies were reversed (Reversal phase) and the previously incorrect stimulus became the correct stimulus. In a final third phase of testing (Novel Stimuli phase), two novel stimuli were introduced, and mice were required to undergo a second round of discrimination testing with these stimuli. In all cases, mice were required to reach a criterion of 70% correct choices during at least two sessions prior to entering the next phase of touchscreen testing. Results: Learning during the Discrimination phase was similar between the 12-month old WT and zQ175 HD groups, but the zQ175 at 6-months old showed decreased accuracy over the last 10 days of Discrimination compared with the corresponding WT controls. During the Reversal and Novel Stimuli phases, zQ175 mice exhibited significant deficits compared to their WT control; reversal learning appeared to exhibit a greater deficit.

Conclusions: The zQ175 HD mouse model exhibited deficits consistent with cognitive inflexibility and psychomotor retardation, a phenotype analogous to cognitive symptoms described in HD patients.