The cerebellum and spatial ability: dissection of motor and cognitive components with a mouse model system

The cerebellum has recently been linked to spatial navigation, as indicated by the inferior performance of cerebellar mutant or cerebellar lesioned animals in the water maze. The inability to dissociate motor from cognitive deficits in the impaired water maze performance has been a confounding variable in previous studies, however. In this study, we sought to define clearly the role of the cerebellar system in spatial navigation outside of motor control by creating a mouse model of Purkinje cell loss with intact motor ability, and testing these mice in the water maze. To this end, we made aggregation chimeras between Lc/+ mice, which lose all Purkinje cells postnatally, and +/+ control mice. Lc/+ mice are ataxic and show impaired rotor-rod performance. By contrast, we show that Lc/+ <----> +/+ chimeras above a threshold of Purkinje cell loss show no outward signs of motor impairment and demonstrated normal rotor-rod ability. In the water maze, we found that Lc/+ mice showed impaired performance in the place, cue and platform removal tasks, whereas Lc/+<---->+/+ chimeras performed similarly to controls in all tasks. We found that the impaired performance in the water maze of Lc/+ mice resulted from both motor as well as cognitive impairment that could be separated from one another by statistical means. In addition, through the analysis of individual chimeric mice, the relationships between these deficits and the total number of Purkinje cells were determined and a specific role for Purkinje cells in search strategy was identified.