Cerebellar Neurodynamics Predict Decision Timing and Outcome on the Single-Trial Level

• Published in: Cell 2020-02, Vol.180 (3), p.536-551.e17
• Main Authors: Lin, Qian, Manley, Jason, Helmreich, Magdalena, Schlumm, Friederike, Li, Jennifer M., Robson, Drew N., Engert, Florian, Schier, Alexander, Nöbauer, Tobias, Vaziri, Alipasha
• Format: Article
• Language: English
• Subjects: action selection; Animals; Behavior, Animal - physiology; Brain Mapping - methods; Cerebellum; Cerebellum - physiology; Cerebrum - physiology; Cognition - physiology; Conditioning, Operant - physiology; decision making; Decision Making - physiology; demixed principal component analysis; Goals; Habenula - physiology; Hot Temperature; Larva - physiology; Light field microscopy; Motor Activity - physiology; motor planning; Movement; Neurons - physiology; operant learning; population ramping activity; Psychomotor Performance - physiology; Reaction Time - physiology; Rhombencephalon - physiology; whole-brain calcium imaging; zebrafish; Zebrafish - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2019.12.018

Goal-directed behavior requires the interaction of multiple brain regions. How these regions and their interactions with brain-wide activity drive action selection is less understood. We have investigated this question by combining whole-brain volumetric calcium imaging using light-field microscopy and an operant-conditioning task in larval zebrafish. We find global, recurring dynamics of brain states to exhibit pre-motor bifurcations toward mutually exclusive decision outcomes. These dynamics arise from a distributed network displaying trial-by-trial functional connectivity changes, especially between cerebellum and habenula, which correlate with decision outcome. Within this network the cerebellum shows particularly strong and predictive pre-motor activity (>10 s before movement initiation), mainly within the granule cells. Turn directions are determined by the difference neuroactivity between the ipsilateral and contralateral hemispheres, while the rate of bi-hemispheric population ramping quantitatively predicts decision time on the trial-by-trial level. Our results highlight a cognitive role of the cerebellum and its importance in motor planning. [Display omitted] •Whole-brain Ca2+ imaging and decision making in larval zebrafish on the single-trial level•Pre-motor bifurcation and trial-by-trial changes of functional connectivity•Cerebellar activity predicts decision outcome and decision time >10 s before movement•Hemisphere difference encodes decision; joint hemisphere activity encodes timing A specific motor decision and its timing can be predicted using information from the cerebellum >10 s before movement, during a cognitive task in larval zebrafish. Decision outcomes and timing can be predicted at the single-trial level, using neuroactivity information from whole-brain Ca2+ imaging, at single-cell resolution.