Cerebellar nuclei output pathways regulate motor and non-motor behaviors through forebrain circuits

The adult cerebellum is involved in modulating most, if not all, behaviors via its direct or indirect projections throughout the central nervous system. Its involvement in higher order behaviors is most prominent in human, where the lateral cerebellum (hemispheres) has expanded along with areas in the cerebral cortex that regulate language, emotions and cognition. An important aspect of wiring of the brain, is how the circuitry is established during normal development and activity, compared to how it is established when a developmental defect occurs, such as an injury that kills cells or a genetic mutation that alters the activity of specific neurons or changes the transcriptional output. One way to assess the impact of these two modes of circuit formation is to compare the robustness of specific behaviors in rodents in the two conditions, and thereby infer what behaviors are normally controlled by specific cerebellar cells/regions and which behavior modules or neural circuits they participate in. Inhibition of groups of neurons in the adult brain has been used to define what behaviors the cells control. While such an approach can define neural circuit function under normal developmental conditions, it does not reveal the underlying ability of the neural circuits to rewire, or wire in a different way when faced with a developmental perturbation. In the latter, cells that normally would be involved in a behavior might no longer control the behavior and instead a new set of neurons might control the behavior. In this chapter, we address these issues by describing what is considered the normal functions of subgroups of the cerebellar nuclei output neurons based on inhibiting/lesioning neurons in the adult and compare this to how the circuits appear to function following disruption of neurons by inhibiting their activity, removing them or introducing gene mutations during development.