A Purkinje cell to parabrachial nucleus pathway enables broad cerebellar influence over the forebrain

Abstract

Abstract In addition to its well-known contributions to motor function, the cerebellum is involved in emotional regulation, anxiety, and affect 1-4 . We found that suppressing the firing of cerebellar Purkinje cells (PCs) rapidly excites forebrain areas that could contribute to such functions (including the amygdala, basal forebrain, and septum), but that the classic cerebellar outputs, the deep cerebellar nuclei (DCN), do not project to these forebrain regions. Here we show that PCs directly inhibit parabrachial nuclei (PBN) neurons that project to and influence numerous forebrain regions in a manner distinct from the DCN pathway. We also found that the PBN and DCN output pathways differentially influence behavior: suppressing the PC to PBN pathway is aversive and does not affect the speed of movement, whereas suppressing the PC to DCN pathway is not aversive and reduces speed. Molecular profiling shows that PCs inhibit numerous types of PBN neurons that control diverse nonmotor behaviors 5-9 . Therefore, the PBN pathway allows the cerebellum to regulate activity in many forebrain regions and may be an important substrate for nonmotor disorders related to cerebellar dysfunction.