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).
Reviewing Editor
- Jennifer L Raymond, Stanford School of Medicine, United States
Version history
- Received: March 12, 2019
- Accepted: July 30, 2019
- Accepted Manuscript published: September 11, 2019 (version 1)
- Version of Record published: November 11, 2019 (version 2)
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.
Metrics
-
- 4,560
- Page views
-
- 744
- Downloads
-
- 63
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
-
- Neuroscience
New studies examine how the different sub-structures in the cerebellum are organized to receive information during complex behavioral tasks
-
- Neuroscience
Even though human experience unfolds continuously in time, it is not strictly linear; instead, it entails cascading processes building hierarchical cognitive structures. For instance, during speech perception, humans transform a continuously varying acoustic signal into phonemes, words, and meaning, and these levels all have distinct but interdependent temporal structures. Time-lagged regression using temporal response functions (TRFs) has recently emerged as a promising tool for disentangling electrophysiological brain responses related to such complex models of perception. Here we introduce the Eelbrain Python toolkit, which makes this kind of analysis easy and accessible. We demonstrate its use, using continuous speech as a sample paradigm, with a freely available EEG dataset of audiobook listening. A companion GitHub repository provides the complete source code for the analysis, from raw data to group level statistics. More generally, we advocate a hypothesis-driven approach in which the experimenter specifies a hierarchy of time-continuous representations that are hypothesized to have contributed to brain responses, and uses those as predictor variables for the electrophysiological signal. This is analogous to a multiple regression problem, but with the addition of a time dimension. TRF analysis decomposes the brain signal into distinct responses associated with the different predictor variables by estimating a multivariate TRF (mTRF), quantifying the influence of each predictor on brain responses as a function of time(-lags). This allows asking two questions about the predictor variables: 1) Is there a significant neural representation corresponding to this predictor variable? And if so, 2) what are the temporal characteristics of the neural response associated with it? Thus, different predictor variables can be systematically combined and evaluated to jointly model neural processing at multiple hierarchical levels. We discuss applications of this approach, including the potential for linking algorithmic/representational theories at different cognitive levels to brain responses through computational models with appropriate linking hypotheses.
