Plastic Changes in Striatal Fast-Spiking Interneurons Following Hemicerebellectomy and Environmental Enrichment

Abstract

Recent findings suggest marked interconnections between the cerebellum and striatum, thus challenging the classical view of their segregated operation in motor control. Therefore, this study was aimed at further investigating this issue by analyzing the effects of hemicerebellectomy (HCb) on density and dendritic length of striatal fast-spiking interneurons (FSi). First, we analyzed the plastic rearrangements of striatal FSi morphology in hemicerebellectomized animals reared in standard conditions. Then, since environmental enrichment (EE) induces structural changes in experimental models of brain disease, we evaluated FSi morphology in lesioned animals exposed to an enriched environment after HCb. Although HCb did not affect FSi density, it progressively shrank dendritic branching of striatal FSi of both sides. These plastic changes, already evident 15days after the cerebellar ablation, became very marked 30days after the lesion. Such a relevant effect was completely abolished by postoperative enrichment. EE not only counteracted shrinkage of FSi dendritic arborization but also provoked a progressive increase in dendritic length which surpassed that of the controls as the enrichment period lengthened. These data confirm that the cerebellum and striatum are more interconnected than previously retained. Furthermore, cerebellar damage likely evokes a striatal response through cortical mediation. The EE probably modifies HCb-induced plastic changes in the striatum by increasing the efficiency of the cortical circuitry. This is the first study describing the morphological rearrangement of striatal FSi following a cerebellar lesion; it provides the basis for further studies aimed at investigating the mechanisms underlying cerebello-striatal "talking."