1. Neuroscience
Download icon

Neural mechanisms of economic choices in mice

  1. Masaru Kuwabara
  2. Ningdong Kang
  3. Timothy E Holy
  4. Camillo Padoa-Schioppa  Is a corresponding author
  1. Washington University in St Louis, United States
Research Article
  • Cited 7
  • Views 2,789
  • Annotations
Cite this article as: eLife 2020;9:e49669 doi: 10.7554/eLife.49669

Abstract

Economic choices entail computing and comparing subjective values. Evidence from primates indicates that this behavior relies on the orbitofrontal cortex. Conversely, previous work in rodents provided conflicting results. Here we present a mouse model of economic choice behavior, and we show that the lateral orbital (LO) area is intimately related to the decision process. In the experiments, mice chose between different juices offered in variable amounts. Choice patterns closely resembled those measured in primates. Optogenetic inactivation of LO dramatically disrupted choices by inducing erratic changes of relative value and by increasing choice variability. Neuronal recordings revealed that different groups of cells encoded the values of individual options, the binary choice outcome and the chosen value. These groups match those previously identified in primates, except that the neuronal representation in mice is spatial (in monkeys it is good-based). Our results lay the foundations for a circuit-level analysis of economic decisions.

Data availability

Data and analysis files included as supplementary information

Article and author information

Author details

  1. Masaru Kuwabara

    Department of Neuroscience, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ningdong Kang

    Department of Neuroscience, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Timothy E Holy

    Department of Neuroscience, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Camillo Padoa-Schioppa

    Department of Neuroscience, Washington University in St Louis, Saint Louis, United States
    For correspondence
    camillo@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7519-8790

Funding

National Institute on Drug Abuse (R21-DA042882)

  • Camillo Padoa-Schioppa

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 conformed to the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee (IACUC) at Washington University in St Louis (protocol # 20160167).

Reviewing Editor

  1. Naoshige Uchida, Harvard University, United States

Publication history

  1. Received: June 25, 2019
  2. Accepted: February 24, 2020
  3. Accepted Manuscript published: February 25, 2020 (version 1)
  4. Version of Record published: March 9, 2020 (version 2)

Copyright

© 2020, Kuwabara 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

  • 2,789
    Page views
  • 468
    Downloads
  • 7
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Yu Takagi et al.
    Research Article

    Choices rely on a transformation of sensory inputs into motor responses. Using invasive single neuron recordings, the evolution of a choice process has been tracked by projecting population neural responses into state spaces. Here we develop an approach that allows us to recover similar trajectories on a millisecond timescale in non-invasive human recordings. We selectively suppress activity related to three task-axes, relevant and irrelevant sensory inputs and response direction in magnetoencephalography data acquired during context-dependent choices. Recordings from premotor cortex show a progression from processing sensory input to processing the response. In contrast to previous macaque recordings, information related to choice-irrelevant features is represented more weakly than choice-relevant sensory information. To test whether this mechanistic difference between species is caused by extensive overtraining common in non-human primate studies, we trained humans on >20,000 trials of the task. Choice-irrelevant features were still weaker than relevant features in premotor cortex after overtraining.

    1. Cell Biology
    2. Neuroscience
    Vladimir Zhemkov et al.
    Research Article

    Sigma 1 receptor (S1R) is a 223-amino-acid-long transmembrane endoplasmic reticulum (ER) protein. S1R modulates activity of multiple effector proteins and is a well-established drug target. However, signaling functions of S1R in cells are poorly understood. Here, we test the hypothesis that biological activity of S1R in cells can be explained by its ability to interact with cholesterol and to form cholesterol-enriched microdomains in the ER membrane. By performing experiments in reduced reconstitution systems, we demonstrate direct effects of cholesterol on S1R clustering. We identify a novel cholesterol-binding motif in the transmembrane region of human S1R. Mutations of this motif impair association of recombinant S1R with cholesterol beads, affect S1R clustering in vitro and disrupt S1R subcellular localization. We demonstrate that S1R-induced membrane microdomains have increased local membrane thickness and that increased local cholesterol concentration and/or membrane thickness in these microdomains can modulate signaling of inositol-requiring enzyme 1α in the ER. Further, S1R agonists cause disruption of S1R clusters, suggesting that biological activity of S1R agonists is linked to remodeling of ER membrane microdomains. Our results provide novel insights into S1R-mediated signaling mechanisms in cells.