Insights into cerebellar development and connectivity

The cerebellum has a well-established role in controlling motor functions such coordination, balance, posture, and skilled learning. There is mounting evidence that it might also play a critical role in non-motor functions such as cognition and emotion. It is therefore not surprising that cerebellar defects are associated with a wide array of diseases including ataxia, dystonia, tremor, schizophrenia, dyslexia, and autism spectrum disorder. What is intriguing is that a seemingly uniform circuit that is often described as being simple should carry out all of these behaviors. Analyses of how cerebellar circuits develop have revealed that such descriptions massively underestimate the complexity of the cerebellum. The cerebellum is in fact highly patterned and organized around a series of parasagittal stripes and transverse zones. This topographic architecture partitions all cerebellar circuits into functional modules that are thought to enhance processing power during cerebellar dependent behaviors. What are arguably the most remarkable features of cerebellar topography are the developmental processes that produce them. This review is concerned with the genetic and cellular mechanisms that orchestrate cerebellar patterning. We place a major focus on how Purkinje cells control multiple aspects of cerebellar circuit assembly. Using this model, we discuss evidence for how zebra-like patterns in Purkinje cells sculpt the cerebellum, how specific genetic cues mediate the process, and how activity refines the patterns into an adult map that is capable of executing various functions. We also discuss how defective Purkinje cell patterning might impact the pathogenesis of neurological conditions.