Cerebellar associative learning underlies skilled reach adaptation

The cerebellum is hypothesized to refine movement through online adjustments. We examined how such predictive control may be generated using a mouse reach paradigm, testing whether the cerebellum uses within-reach information as a predictor to adjust reach kinematics. We first identified a populatio...

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Bibliographic Details
Published in:Nature neuroscience 2023-06, Vol.26 (6), p.1068-1079
Main Authors: Calame, Dylan J., Becker, Matthew I., Person, Abigail L.
Format: Article
Language:English
Subjects:
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Adaptation
Animal Genetics and Genomics
Associative learning
Behavioral Sciences
Biological Techniques
Biomedical and Life Sciences
Biomedicine
Cerebellum
Cerebellum - physiology
Closed loops
Conditioning, Classical
Kinematics
Learning
Motor skill
Movement - physiology
Neurobiology
Neurosciences
Perturbation
Predictive control
Purkinje Cells
Stimulation
Variables
Velocity
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Summary:The cerebellum is hypothesized to refine movement through online adjustments. We examined how such predictive control may be generated using a mouse reach paradigm, testing whether the cerebellum uses within-reach information as a predictor to adjust reach kinematics. We first identified a population-level response in Purkinje cells that scales inversely with reach velocity, pointing to the cerebellar cortex as a potential site linking kinematic predictors and anticipatory control. Next, we showed that mice can learn to compensate for a predictable reach perturbation caused by repeated, closed-loop optogenetic stimulation of pontocerebellar mossy fiber inputs. Both neural and behavioral readouts showed adaptation to position-locked mossy fiber perturbations and exhibited aftereffects when stimulation was removed. Surprisingly, position-randomized stimulation schedules drove partial adaptation but no opposing aftereffects. A model that recapitulated these findings suggests that the cerebellum may decipher cause-and-effect relationships through time-dependent generalization mechanisms. This study tests a key hypothesis of cerebellar motor correction, showing that inputs to the cerebellum that drive errors during skilled movements are rapidly adjusted over trials to enhance motor accuracy.
ISSN:1097-6256
1546-1726
DOI:10.1038/s41593-023-01347-y