Involvement of cerebellar Purkinje cells in adaptive locomotion of larval zebrafish

Animals need to adapt their behavior to survive and be successful in a constantly changing environment. Behavioral adaptations can be evoked by two mechanisms: feedback control and internal models. A feedback controller compares current sensory state with desired state and generates a motor output that minimizes their difference; such simple controllers can produce adaptive behavior without changing their own intrinsic parameters. In the central nervous system, however, feedback control is limited by long temporal delays associated with sensory processing required to estimate current sensory state. To overcome this limitation, internal models learn previous sensory-motor history to update parameters of motor control in a predictive manner. In the present study, I use multiple perturbations in visual feedback to show that larval zebrafish acutely adapt their swimming behavior to these perturbations. These acute behavioral changes do not affect an initial stereotyped ballistic portion of the swimming bouts that lasts ~ 220 ms and are unaffected by a pharmaco-genetic ablation of Purkinje cells – the major locus of internal models, suggesting that acute adaptation results from a feedback control mechanism. I support this hypothesis by modelling a simple feedback controller that is based on temporal integration of sensory evidence. The controller is able to closely reproduce all observed aspects of acute adaptation. The main assumption of the model: existence of temporal sensory integration in the larval zebrafish brain is supported by whole-brain functional imaging. On the other hand, during long-term adaptation, larval zebrafish gradually change their behavior, including their swimming kinematics during the ballistic period. In contrast with the acute short-term changes, these behavioral alterations are cerebellum-dependent. In conclusion, adaptive locomotion in larval zebrafish should be understood as a feedback control system whose intrinsic parameters can be modified by cerebellar output.