Tyrosine hydroxylase- and dopamine transporter-immunoreactive axons in the primate cerebellum. Evidence for a lobular- and laminar-specific dopamine innervation

Abstract

The cerebellum seems to play a critical role in many motor and cognitive functions, including those that are disturbed in schizophrenia. Although dopamine is known to influence the motor or cognitive functions mediated by other brain regions and to play a role in the pathophysiology of schizophrenia, the cerebellum has not been thought to be a target of dopamine-containing axons. However, given recent reports of dopamine receptors in the cerebellum, we sought to determine whether axons immunoreactive for the proteins involved in dopamine synthesis and reuptake are present in the cerebellum of macaque monkeys. We found that axons immunoreactive for the dopamine membrane transporter, a specific marker of dopamine axons, were present in high density, but only in certain lobules of the cerebellar vermis. In addition, these axons were found principally in the granule cell layer, where they densely arborized immediately subjacent to the Purkinje cells. Similarly, axons labeled for tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, were also present in high density in the granule cell layer of the same lobules of the vermis. In contrast, axons immunoreactive for dopamine beta-hydroxylase, a marker of noradrenergic axons, exhibited a different and more widespread pattern of innervation. These findings are consistent with a dopamine innervation of the primate cerebellum that is both lobular- and laminar-specific, and they suggest that dopamine may play a role in certain cerebellar functions.