Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum

Abstract

The most noticeable morphological feature of the cerebellum is its folded appearance, whereby fissures separate its anterior-posterior extent into lobules. Each lobule is molecularly coded along the medial-lateral axis by parasagittal stripes of gene expression in one cell type, the Purkinje cells (PCs). Additionally, within each lobule distinct combinations of afferents terminate and supply the cerebellum with synchronized sensory and motor information. Strikingly, afferent terminal fields are organized into parasagittal domains, and this pattern bears a close relationship to PC molecular coding. Thus, cerebellum three-dimensional complexity obeys a basic coordinate system that can be broken down into morphology and molecular coding. In this review, we summarize the sequential stages of cerebellum development that produce its laminar structure, foliation, and molecular organization. We also introduce genes that regulate morphology and molecular coding, and discuss the establishment of topographical circuits within the context of the two coordinate systems. Finally, we discuss how abnormal cerebellar organization may result in neurological disorders like autism.