Impaired acquisition of a Morris water maze task following selective destruction of cerebellar purkinje cells with OX7-saporin

Spatial learning in the Morris water maze task is believed to be dependent on an intact hippocampal system. However, evidence from human studies and animal experiments suggests a potential cerebellar involvement in spatial processing, place learning, and other types of 'higher-order' cognition. In order to investigate this possibility, intraventricular injections (ICV) of the anti-neuronal immunotoxin OX7-saporin were used to selectively destroy cerebellar Purkinje cells, without affecting other brain areas believed to be critically involved in spatial learning and memory. Bilateral ICV injections of 2 mu g OX7-saporin (4 mu g total) in adult male rats produced substantial loss of Purkinje cells (56%) throughout the cerebellum without affecting hippocampal morphology or biochemical indices of cholinergic, serotonergic, or catecholaminergic function in the hippocampus, frontal cortex, or striatum. ICV OX7-saporin significantly impaired acquisition and performance of the standard Morris water maze task (though the impairment was less severe than reported in earlier studies that used alternate lesion methods or mutant mice species), but did not alter performance on the cued version of the task, or locomotor activity. In addition, lesioned animals spent significantly less time in the target quadrant on probe trial days 4 and 7 and the average distance to target scores (ADT) were significantly greater than controls on those days. Swim speed was not affected. Based on the specificity of the behavioral and neurobiological alterations, these data support the hypothesis that the cerebellum is involved in spatial processing and place learning. (C) 2000 Elsevier Science B.V. All rights reserved.