1. Neuroscience
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Midbrain dopamine neurons compute inferred and cached value prediction errors in a common framework

  1. Brian F Sadacca
  2. Joshua L Jones
  3. Geoffrey Schoenbaum  Is a corresponding author
  1. National Institutes of Health, United States
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Cite this article as: eLife 2016;5:e13665 doi: 10.7554/eLife.13665

Abstract

Midbrain dopamine neurons have been proposed to signal reward prediction errors as defined in temporal difference (TD) learning algorithms. While these models have been extremely powerful in interpreting dopamine activity, they typically do not use value derived through inference in computing errors. This is important because much real world behavior - and thus many opportunities for error-driven learning - is based on such predictions. Here, we show that error-signaling rat dopamine neurons respond to the inferred, model-based value of cues that have not been paired with reward and do so in the same framework as they track the putative cached value of cues previously paired with reward. This suggests that dopamine neurons access a wider variety of information than contemplated by standard TD models and that, while their firing conforms to predictions of TD models in some cases, they may not be restricted to signaling errors from TD predictions.

Article and author information

Author details

  1. Brian F Sadacca

    Intramural Research program of the National Institute on Drug Abuse, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Joshua L Jones

    Intramural Research program of the National Institute on Drug Abuse, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Geoffrey Schoenbaum

    Intramural Research program of the National Institute on Drug Abuse, National Institutes of Health, Bethesda, United States
    For correspondence
    geoffrey.schoenbaum@nih.gov
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Experiments were performed at the National Institute on Drug Abuse Intramural Research Program in accordance with NIH guidelines and an approved institutional animal care and use committee protocol (15-CNRB-108). The protocol was approved by the ACUC at NIDA-IRP (Assurance Number: A4149-01).

Reviewing Editor

  1. Timothy EJ Behrens, University College London, United Kingdom

Publication history

  1. Received: December 9, 2015
  2. Accepted: March 3, 2016
  3. Accepted Manuscript published: March 7, 2016 (version 1)
  4. Version of Record published: March 16, 2016 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Further reading

Further reading

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    The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation.