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 a nimal experiments suggests a potential cerebellar involvement in spatial pr ocessing, place learning, and other types of 'higher-order' cognition. In o rder 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 inject ions of 2 mu g OX7-saporin (4 mu g total) in adult male rats produced subst antial loss of Purkinje cells (56%) throughout the cerebellum without affec ting hippocampal morphology or biochemical indices of cholinergic, serotone rgic, or catecholaminergic function in the hippocampus, frontal cortex, or striatum. ICV OX7-saporin significantly impaired acquisition and performanc e of the standard Morris water maze task (though the impairment was less se vere 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 signi ficantly less time in the target quadrant on probe trial days 4 and 7 and t he average distance to target scores (ADT) were significantly greater than controls on those days. Swim speed was not affected. Based on the specifici ty of the behavioral and neurobiological alterations, these data support th e hypothesis that the cerebellum is involved in spatial processing and plac e learning. (C) 2000 Elsevier Science B.V. All rights reserved.