Cerebellar Outputs Through an Unconventional Nucleus

The cerebellum is no longer just a motor structure. Human imaging studies have pointed to links between the cerebellum and cognition, language, and affect. Preclinical work has also indicated that the cerebellum has many nonmotor functions ranging from aggression to sleep. Expression of autism related proteins within cerebellar principle neurons (Purkinje cells) is sufficient to recapitulate many hallmarks of the condition in mice. These Purkinje cells send their projections to the deep cerebellar nuclei (DCN) and vestibular nuclei (VN), often considered the only cerebellar output nuclei. However, the known output pathways that connect the cerebellum with the forebrain seem insufficient to explain the diversity of behaviors now associated with it. We found that there is an additional, underappreciated output pathway through the parabrachial nucleus that receives direct Purkinje cell input and projects to the forebrain. Unlike the conventional cerebellar outputs, this pathway has significant projections to the amygdala, basal forebrain, prefrontal cortex and others. The aim of this project is to characterize cerebellar inputs to the parabrachial and identify these novel cerebellar output targets. We will focus on the projection to the amygdala. There is a rich behavioral literature describing the cerebellum as a core component in fear extinction, though there is no known neural substrate underlying this. In humans, trauma to the cerebellum is a strong predictor of post- traumatic stress disorder. We will test whether this unconventional cerebellar output can potentially mediate this nonmotor behavior.