Distinct temporal difference error signals in dopamine axons in three regions of the striatum in a decision-making task
- Harvard University, United States
Abstract
Different regions of the striatum regulate different types of behavior. However, how dopamine signals differ across striatal regions and how dopamine regulates different behaviors remain unclear. Here, we compared dopamine axon activity in the ventral, dorsomedial, and dorsolateral striatum, while mice performed a perceptual and value-based decision task. Surprisingly, dopamine axon activity was similar across all three areas. At a glance, the activity multiplexed different variables such as stimulus-associated values, confidence and reward feedback at different phases of the task. Our modeling demonstrates, however, that these modulations can be inclusively explained by moment-by-moment changes in the expected reward, i.e. the temporal difference error. A major difference between areas was the overall activity level of reward responses: reward responses in dorsolateral striatum were positively shifted, lacking inhibitory responses to negative prediction errors. The differences in dopamine signals put specific constraints on the properties of behaviors controlled by dopamine in these regions.
Data availability
A source code file has been provided for Figure 7. Fluorometry data has been deposited in Dryad available at: doi:10.5061/dryad.pg4f4qrmf.
-
Fluorometry DataDryad Digital Repository, doi:10.5061/dryad.pg4f4qrmf.
Article and author information
Author details
Mitsuko Watabe-Uchida
Funding
Japan Society for the Promotion of Science
- Iku Tsutsui-Kimura
Japan Society for the Promotion of Science
- Hideyuki Matsumoto
National Institute of Mental Health (R01MH095953,R01MH101207,R01MH110404,R01NS108740)
- Naoshige Uchida
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 procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Harvard Animal Care and Use Committee (protocol #26-03). All surgeries were performed under aseptic conditions with animals anesthetized with isoflurane (1-2% at 0.5-1.0 l/min). Analgesia was administered pre (buprenorphine, 0.1 mg/kg, I.P) and postoperatively (ketoprofen, 5 mg/kg, I.P).
Copyright
© 2020, Tsutsui-Kimura et al.
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
-
- 5,301
- views
-
- 796
- downloads
-
- 85
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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)
Distinct temporal difference error signals in dopamine axons in three regions of the striatum in a decision-making task
eLife 9:e62390.
https://doi.org/10.7554/eLife.62390
Further reading
-
- Neuroscience
What determines where to move the eyes? We recently showed that pupil size, a well-established marker of effort, also reflects the effort associated with making a saccade (‘saccade costs’). Here, we demonstrate saccade costs to critically drive saccade selection: when choosing between any two saccade directions, the least costly direction was consistently preferred. Strikingly, this principle even held during search in natural scenes in two additional experiments. When increasing cognitive demand experimentally through an auditory counting task, participants made fewer saccades and especially cut costly directions. This suggests that the eye-movement system and other cognitive operations consume similar resources that are flexibly allocated among each other as cognitive demand changes. Together, we argue that eye-movement behavior is tuned to adaptively minimize saccade-inherent effort.
-
- Neuroscience
The increasing use of tissue clearing techniques underscores the urgent need for cost-effective and simplified deep imaging methods. While traditional inverted confocal microscopes excel in high-resolution imaging of tissue sections and cultured cells, they face limitations in deep imaging of cleared tissues due to refractive index mismatches between the immersion media of objectives and sample container. To overcome these challenges, the RIM-Deep was developed to significantly improve deep imaging capabilities without compromising the normal function of the confocal microscope. This system facilitates deep immunofluorescence imaging of the prefrontal cortex in cleared macaque tissue, extending imaging depth from 2 mm to 5 mm. Applied to an intact and cleared Thy1-EGFP mouse brain, the system allowed for clear axonal visualization at high imaging depth. Moreover, this advancement enables large-scale, deep 3D imaging of intact tissues. In principle, this concept can be extended to any imaging modality, including existing inverted wide-field, confocal, and two-photon microscopy. This would significantly upgrade traditional laboratory configurations and facilitate the study of connectomes in the brain and other tissues.
