Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum
- Duke University School of Medicine, United States
Abstract
Classical models of cerebellar learning posit that climbing fibers operate according to a supervised learning rule to instruct changes in motor output by signaling the occurrence of movement errors. However, cerebellar output is also associated with non-motor behaviors, and recently with modulating reward association pathways in the VTA. To test how the cerebellum processes reward related signals in the same type of classical conditioning behavior typically studied to evaluate reward processing in the VTA and striatum, we have used calcium imaging to visualize instructional signals carried by climbing fibers across the lateral cerebellum in mice before and after learning. We find distinct climbing fiber responses in three lateral cerebellar regions that can each signal reward prediction. These instructional signals are well suited to guide cerebellar learning based on reward expectation and enable a cerebellar contribution to reward driven behaviors, suggesting a broad role for the lateral cerebellum in reward-based learning.
Data availability
Datasets supporting the findings of this study are ~50 GB per experiment, and are therefore available through a request to the corresponding author. Processed data have been provided for each figure, and analysis code has been place in GitHub (https://github.com/Glickfeld-And-Hull-Laboratories/Heffley_Hull_2019_eLife).
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (5R01NS096289)
- Court Hull
National Institute of Neurological Disorders and Stroke (F31NS103425)
- William Heffley
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures using animals were carried out with the approval of the Duke University Animal Care and Use Committee (protocol #A010-19-01).
Copyright
© 2019, Heffley & Hull
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum
eLife 8:e46764.
https://doi.org/10.7554/eLife.46764
Further reading
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- Neuroscience
New studies examine how the different sub-structures in the cerebellum are organized to receive information during complex behavioral tasks
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- Neuroscience
Each sensory modality has its own primary and secondary thalamic nuclei. While the primary thalamic nuclei are well understood to relay sensory information from the periphery to the cortex, the role of secondary sensory nuclei is elusive. We trained head-fixed mice to attend to one sensory modality while ignoring a second modality, namely to attend to touch and ignore vision, or vice versa. Arrays were used to record simultaneously from the secondary somatosensory thalamus (POm) and secondary visual thalamus (LP). In mice trained to respond to tactile stimuli and ignore visual stimuli, POm was robustly activated by touch and largely unresponsive to visual stimuli. A different pattern was observed when mice were trained to respond to visual stimuli and ignore touch, with POm now more robustly activated during visual trials. This POm activity was not explained by differences in movements (i.e. whisking, licking, pupil dilation) resulting from the two tasks. Post hoc histological reconstruction of array tracks through POm revealed that subregions varied in their degree of plasticity. LP exhibited similar phenomena. We conclude that behavioral training reshapes activity in secondary thalamic nuclei. Secondary nuclei respond to the same behaviorally relevant, reward-predicting stimuli regardless of stimulus modality.
