Although there is no evidence of neurodegeneration in DYT1 dystonia, the cascade of events which are triggered by the mutant TA and lead to dystonic movements is still unknown. Recent evidence from both clinical studies and animal models point to a concomitant involvement of two sensorimotor regions, basal ganglia and cerebellar pathways, thus supporting the hypothesis that dystonia may represent a neurodevelopmental circuit disorder. TA is typically localized in the endoplasmic reticulum and in the inner nuclear membrane and thought to be retained there by association with membrane spanning proteins. In neuronal cell culture, TA was found also throughout the cytoplasm, neurite processes, and growth cones. By interacting with the cytoskeletal network it can play important roles for neuronal maturation such as cell adhesion, neurite extension, and cytoskeletal dynamics. Recent evidence highlights a new function for TA in endoplasmic reticulumassociated degradation in response to stress. Interestingly, it plays also a regulatory role in the secretory pathway, in the synaptic vesicle Salvianolic-acid-B transport, turnover, and transmitter release. Accordingly, TA has been found enriched in synaptosomal membrane fractions at ultrastructural level within axons and presynaptic terminals. Despite such evidence, a detailed analysis of the cellular and synaptic distribution of TA is still lacking. Immunolocalization of TA in adult human, rat and mouse cerebellum showed an abundant expression of the protein in PC soma and proximal dendrite. Of note, the protein reaches the peak of expression in rodent cerebellum around postnatal day 14, virtually corresponding to childhood in humans, a period when cerebellar neurons undergo extensive axonal outgrowth, dendritic branching, and synaptic remodelling. To better clarify the potential role of TA in the cerebellar neurodevelopment, we characterized its expression profile in the cerebellum of normal juvenile mice. In addition, since scarce information is available on TA localization at synaptic terminals, we performed by a quantitative confocal analysis a detailed study of its expression within the main GABA-ergic and glutamatergic inputs of the cerebellar circuitry. In the present study we examined the expression of TA in different cell populations 
of the juvenile mouse cerebellum, pointing to its localization in the main GABA-ergic and glutamatergic synaptic terminals. First, we observed that TA was broadly distributed in the cerebellar Dexrazoxane hydrochloride cortex and DCN without a preferential expression in specific neuronal subtypes. In addition three relevant, novel observations emerged: TA was localized in the spines of PCs; TA was expressed in the main GABA-ergic and glutamatergic synaptic terminals of the cerebellar cortex; TA was clearly expressed also in glial cells. A novel finding of this work, is represented by the characterization of TA expression in the synaptic terminals during postnatal development, at P14, when TA reaches the peak of its expression and cerebellar synaptogenesis occurs. Of note, we conducted a rigorous quantitative analysis by using two different colocalization methods: the first provided the overlap coefficient r for each set of synaptic structures accompanied by the relative negative controls; the second provided the ICQ value for single contacts in the z-dimension. In addition, we supported TA localization in cerebellar synaptic structures by means of western blot analysis of synaptosomal preparations. By means of immunofluorescence experiments we observed a staining pattern of TA protein similar to that described previously by immunohistochemistry in adult human and rodent cerebellum.