Project Summary/Abstract The cerebellum is a brain structure found in all vertebrates, and it has been studied for decades primarily for its role in coordinating motor activity. More recently, an abundance of evidence has surfaced linking the cerebellum to cognitive functions, such as working memory and reward prediction. It is known that the cerebellum is anatomically connected to the cerebral cortex, and specifically to multiple regions known to be important for supporting memory and reward-learning functions. However, it remains unknown how the cerebellum contributes to these cognitive functions, and more generally, what cellular and circuit mechanisms it employs to process information. To advance our understanding of this region and its role in disease, we will use a mouse behavioral paradigm that will allow us to investigate the cellular activity of the cerebellum, and to characterize how it computes information to make these contributions to behavior. We have developed a behavioral task that is well suited to quantitatively address these questions. We will employ modern technologies to image and manipulate the activity of cerebellar neurons in awake, behaving mice performing the task. With two-photon microscopy and genetically encoded calcium indicators, we will visualize the live activity of hundreds of neurons simultaneously while mice behave. With optogenetics, we will inactivate the cerebellum during temporally precise phases of the behavior. This will allow us to determine which aspects of behavior are dependent upon cerebellum. These experiments will enable us to characterize the relationship between the activity of cerebellar neuronal networks and behavior. By studying cerebellar activity at the level of neural circuits during behavior, we will characterize how the cerebellum contributes to normal and abnormal cognitive function. With improved characterization of the circuits that are commonly dysfunctional in prevalent neuropsychiatric diseases like autism and schizophrenia, we will come closer to understanding the underlying causes of these disorders and of normal brain function.