Disorders of the basal ganglia such as Parkinson's disease (PD) and Huntington's disease are commonly thought of primarily as motor disorders; however, the cognitive symptoms of these diseases such as executive dysfunction, learning, memory and attention deficits are prominent and often more disabling than the hallmark motor symptoms. Cognitive features of PD are often neglected in preclinical studies of PD, likely due to the lack of available animal models to study them. ak mice, which are deficient in the transcription factor Pitx3, model the selective nigrostriatal DA loss in PD. Here we report that ak mice are impaired in striatum-dependent cognitive tasks including rotarod learning, t-maze and inhibitory avoidance tasks, but not the striatum-independent social transmission of food preference task. These results suggest that some neuropsychiatric symptoms in PD are related to the pathophysiology of the disease rather than stress associated with disease burden, or medications used to treat PD. Furthermore aphakia mice may be used as a novel model of non-motor symptoms in PD. Keywords cognition; Parkinson's disease; pitx3; dopamine; striatum Parkinson's disease is often characterized as a movement disorder, however, studies show that frequently a major complaints of patients with PD are the non-motor and neuropsychiatric symptoms such as cognitive impairment, depression, anxiety and sleep disturbances. Interestingly, these cognitive symptoms can have a greater impact on quality of life measures than the hallmark motor symptoms of PD (Lauterbach 2005). Up to 80% of patients with PD show symptoms of cognitive impairment ranging from frank dementia and executive dysfunction to more subtle memory loss (Agid, Ruberg et al. 1986;Bosboom, Stoffers et al.
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