RIM is essential for stimulated but not spontaneous somatodendritic dopamine release in the midbrain

  1. Brooks G Robinson  Is a corresponding author
  2. Xintong Cai
  3. Jiexin Wang
  4. James R Bunzow
  5. John T Williams
  6. Pascal S Kaeser  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. Harvard Medical School, United States

Abstract

Action potentials trigger neurotransmitter release at active zones, specialized release sites in axons. Many neurons also secrete neurotransmitters or neuromodulators from their somata and dendrites. However, it is unclear whether somatodendritic release employs specialized sites for release, and the molecular machinery for somatodendritic release is not understood. Here, we identify an essential role for the active zone protein RIM in stimulated somatodendritic dopamine release in the midbrain. In mice in which RIMs are selectively removed from dopamine neurons, action potentials failed to evoke significant somatodendritic release detected via D2 receptor-mediated currents. Compellingly, spontaneous dopamine release was normal upon RIM knockout. Dopamine neuron morphology, excitability, and dopamine release evoked by amphetamine, which reverses dopamine transporters, were also unaffected. We conclude that somatodendritic release employs molecular scaffolds to establish secretory sites for rapid dopamine signaling during firing. In contrast, basal release that is independent of action potential firing does not require RIM.

Data availability

All data generated during this study are included in the figures with individual data points shown in each figure whenever possible.

Article and author information

Author details

  1. Brooks G Robinson

    The Vollum Institute, Oregon Health and Science University, Portland, United States
    For correspondence
    robinbro@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5020-531X
  2. Xintong Cai

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jiexin Wang

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. James R Bunzow

    The Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. John T Williams

    The Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0647-6144
  6. Pascal S Kaeser

    Department of Neurobiology, Harvard Medical School, Boston, United States
    For correspondence
    kaeser@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1558-1958

Funding

National Institute of Neurological Disorders and Stroke (R01NS083898)

  • Pascal S Kaeser

National Institute on Drug Abuse (R01DA04523)

  • John T Williams

National Institute of Neurological Disorders and Stroke (R01NS103484)

  • Pascal S Kaeser

National Institute on Drug Abuse (K99DA044287)

  • Brooks G Robinson

Harvard Medical School

  • Pascal S Kaeser

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Olivier J Manzoni, Aix-Marseille University, INSERM, INMED, France

Ethics

Animal experimentation: All animal experiments were performed according to institutional guidelines of Harvard University and of Oregon Health & Science University, and were in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The animals were handled according to protocols (protocol numbers Harvard IS00000049, OHSU IP00000160) approved by the institutional animal care and use committee (IACUC).

Version history

  1. Received: April 26, 2019
  2. Accepted: September 4, 2019
  3. Accepted Manuscript published: September 5, 2019 (version 1)
  4. Version of Record published: September 20, 2019 (version 2)

Copyright

© 2019, Robinson 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.

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  1. Brooks G Robinson
  2. Xintong Cai
  3. Jiexin Wang
  4. James R Bunzow
  5. John T Williams
  6. Pascal S Kaeser
(2019)
RIM is essential for stimulated but not spontaneous somatodendritic dopamine release in the midbrain
eLife 8:e47972.
https://doi.org/10.7554/eLife.47972

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https://doi.org/10.7554/eLife.47972