Behavioral Characterization of Quinolinate-Induced Lesions of the Medial Striatum: Relevance for Huntington's Disease

Abstract

Huntington’s disease (HD) is an inherited neurodegenerative disorder in which the striatum undergoes marked atrophic changes. Patients with HD typically have impaired cognitive function, including deficient visuospatial skills, lack of cognitive flexibility and poor recall of memories. The relationship between these cognitive abnormalities and the striatal degeneration of HD is incompletely understood. In order to explore this issue, we studied the behavior of rats with histologically confirmed bilateral quinolinate (QUIN)-induced lesions of the medial striatum. In a series of Morris Water Maze (MWM) experiments and Delayed Alternation (DA) tests, QUIN-lesioned animals exhibited: (i) impaired acquisition of visuospatial skills; (ii) impaired “transfer of learning”; (iii) perseverative behavior; (iv) deficient retrieval or retention of stored memories. The lesioned rats were unimpaired when swimming to a visible platform, while moving spontaneously in behavior boxes, and when performing various specialized tests of motor function. These results indicate that QUIN-induced lesions of the medial striatum can produce impairments of visuospatial skills, cognitive flexibility, and recall. These are the categories of cognitive function that are disturbed in HD. This suggests that the striatal degeneration of HD could be a sufficient explanation for the cognitive abnormalities associated with the illness.