Grant: Project Grant

The cerebellum coordinates sensory, motor, and cognitive functions, and in cerebellum-linked disorders, incoordination has been observed widely, such as ataxias, ADHD, and autism. However, it is unclear how the cerebellum coordinates various information during goal-directed behaviors. Given the abundance of cerebellar neurons and the highly repetitive feedforward structure, we hypothesize an orthogonal encoding strategy, which means encoding and separating various signals by presenting them with different neuronal populations. To test this hypothesis, we will combine whole-brain 2-photon calcium imaging of zebrafish, an array of behavioral tasks, optogenetics, and computational tools to study cerebellar neural dynamics. First, to probe how the cerebellum handles distractions, we will introduce task-irrelevant cues as distractions in ROAST and identify the associated cerebellar neural dynamics. Second, to dissect various cerebellar signals, we will investigate motor planning and reward-related activity by dissociating different cell types and adapting ROAST. Finally, to create the discrepancy between the movements and the sensory feedback, we will develop a virtual reality platform compatible with 2-photon recording, manipulate the visual feedback of the motor output, and identify the cerebellar encoding scheme for sensory-motor mismatch during continuous sensory-motor flow. Taken together, this proposal will tackle how the cerebellum coordinates diverse information, handles distracting stimuli, and processes mismatched sensory feedback. Our research will solve fundamental questions in brain science, including the central role of the cerebellum and how it handles distraction and prediction error. Additionally, this will provide more precise targets and patterns for deep brain stimulation, facilitating therapeutic strategies for cerebellar-related disorders.