Dopamine transporters in the cerebellum of mutant mice

Abstract

In the central nervous system, dopamine is known to play a critical role in motor and cognitive functions. Although the cerebellum plays a role in the control of movement and posture and in cognitive functions, it has not been considered to be a dopaminergic region and the dopamine present was thought to represent a precursor of noradrenaline. However, recent evidence suggests that in the cerebellum there is a small dopaminergic element, whose properties are similar to the well characterized system of striatum. In order to better understand the functional role of this system and to delineate its specific interactions within the cerebellum, the distribution and properties of dopamine transporter (DAT) in the cerebellum of reeler and Purkinje cell degeneration (Nna1pcd) mutant mice, which are characterized by severe loss of different cell populations and abnormalities in synapse formation, have been studied. Kinetic studies revealed that [3H]dopamine is transported into cerebellar synaptosomes prepared from normal mice with affinities similar to that into striatal synaptosomes but with much lower maximal velocities. In reeler cerebellar synaptosomes the number of transport sites is significantly reduced. In Nna1pcd cerebellar synaptosomes the kinetic properties of transport of [3H]dopamine are similar to the normal. However, in vitro quantitative DAT autoradiography revealed a significantly increased binding in cerebellar nuclei, a decreased binding in molecular layer and an unaltered binding in the granule cell layer. These observations confirm a dopaminergic innervation of the cerebellum and contribute to our understanding of the intracerebellar distribution of the dopaminergic system.