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The aim of the present study was to investigate whether the cerebellar structures are involved in functions requiring cognitive flexibility abilities. The flexibility of the hemicerebellectomized and control animals in learning a four-choice learning task, adapting to ever-changing response rules was investigated. While in the initial phase of the task both experimental groups exhibited similar performances, only the control animals significantly improved their performance as the sessions went by. The lack of improvement in lesioned animals' performance rendered their responses particularly defective in the final phases of the task, when conversely intact animals performed best, exploiting their "learning to learn" ability. The findings demonstrate the defective influence of the cerebellar lesion on the acquisition, not the execution, of new responses. The results underline the crucial role of the cerebellum in mediating cognitive flexibility behaviors.

To experimentally verify the reserve hypothesis, the influence of rearing conditions on the cognitive performances and on dendritic spines following basal forebrain lesions was analyzed. Adult rats reared in enriched or standard conditions were depleted of the cholinergic projection to the neocortex by 192 IgG-saporin injection into Ch4 region of basal forebrain. Their performance in spatial tasks was compared with that of intact animals reared in analogous conditions. Furthermore, number and density of dendritic spines of the layer-III parietal pyramidal neurons were analyzed. Cholinergic depletion of forebrain cortex resulted in impaired performances in most behavioral tasks in animals reared in standard conditions. Conversely, the enriched lesioned animals did not exhibit most deficits evoked by cholinergic lesion, even if some deficits, such as perseverative behaviors, were still present. The pyramidal neurons exhibited an increased spine number and density in the lesioned animals reared in standard conditions. In the enriched lesioned animals, the enhancement of spine number and density elicited by the rearing condition was fully maintained but not further increased in the presence of the lesion. Thus, rearing in an enriched environment results in the development of brain and cognitive reserves that reduce the cognitive impairment following forebrain lesions.