The role of cerebellar circuits in motor adaptation in zebrafish

• Applicant: Professor Dr. Ruben Portugues
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 399259032

A hindbrain structure known as the cerebellum has long been considered an important center in the brain for coordinating incoming sensory information with the control of motor movements. There is strong experimental evidence from human clinical studies as well as animal models for the necessity of an intact cerebellum for proper motor control and learning. However, it has been a great challenge to understand how motor-related information is encoded in neurons of the cerebellum due to the overwhelming complexity of these circuits in the mammalian brain and the difficulty of recording neural activity in behaving animals. We propose to study how motor information is encoded in the cerebellum of a simple vertebrate, the larval zebrafish, and how these cerebellar circuits control and modify behavior. The larval zebrafish cerebellum is evolutionarily conserved but much simpler than its mammalian counterpart, with fewer neurons and synaptic connections, and offers several experimental advantages. First, we will investigate how natural sensory and motor information are encoded in vivo in the activity of principal cerebellar neurons, the Purkinje cells, in the awake zebrafish as visual stimuli are delivered in a virtual reality environment. Next, we will correlate in vivo neural activity patterns with the animal’s performance in a behavioral task that requires ongoing motor adjustments in response to changing visual feedback. We will then precisely manipulate neural activity with genetically-encoded optical tools to evaluate a causal role of Purkinje cell activity in driving adaptive motor behavior. Finally, we will use our experimental results to develop a computational framework of how sensorimotor information is integrated and transformed by cerebellar Purkinje cells into adaptive motor behaviors. This project will be of broad interest to both researchers in the field of sensory coding and motor control as well as clinicians because it will address the significant question of how motor activity is encoded and transformed in a behaving animal as it interacts with its environment and thus will help elucidate the origin of motor dysfunction seen in cerebellar disorders.

• DFG Programme: Research Grants