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.

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).

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.

Metrics

  • 2,311
    views
  • 344
    downloads
  • 39
    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)

  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

Share this article

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

Further reading

    1. Neuroscience
    Célian Bimbard, Flóra Takács ... Philip Coen
    Tools and Resources

    Electrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically. An ideal chronic implant should (1) allow stable recordings of neurons for weeks; (2) allow reuse of the probes after explantation; (3) be light enough for use in mice. Here, we present the ‘Apollo Implant’, an open-source and editable device that meets these criteria and accommodates up to two Neuropixels 1.0 or 2.0 probes. The implant comprises a ‘payload’ module which is attached to the probe and is recoverable, and a ‘docking’ module which is cemented to the skull. The design is adjustable, making it easy to change the distance between probes, the angle of insertion, and the depth of insertion. We tested the implant across eight labs in head-fixed mice, freely moving mice, and freely moving rats. The number of neurons recorded across days was stable, even after repeated implantations of the same probe. The Apollo implant provides an inexpensive, lightweight, and flexible solution for reusable chronic Neuropixels recordings.

    1. Neuroscience
    Ana Fló, Lucas Benjamin ... Ghislaine Dehaene-Lambertz
    Research Article

    Interest in statistical learning in developmental studies stems from the observation that 8-month-olds were able to extract words from a monotone speech stream solely using the transition probabilities (TP) between syllables (Saffran et al., 1996). A simple mechanism was thus part of the human infant’s toolbox for discovering regularities in language. Since this seminal study, observations on statistical learning capabilities have multiplied across domains and species, challenging the hypothesis of a dedicated mechanism for language acquisition. Here, we leverage the two dimensions conveyed by speech –speaker identity and phonemes– to examine (1) whether neonates can compute TPs on one dimension despite irrelevant variation on the other and (2) whether the linguistic dimension enjoys an advantage over the voice dimension. In two experiments, we exposed neonates to artificial speech streams constructed by concatenating syllables while recording EEG. The sequence had a statistical structure based either on the phonetic content, while the voices varied randomly (Experiment 1) or on voices with random phonetic content (Experiment 2). After familiarisation, neonates heard isolated duplets adhering, or not, to the structure they were familiarised with. In both experiments, we observed neural entrainment at the frequency of the regularity and distinct Event-Related Potentials (ERP) to correct and incorrect duplets, highlighting the universality of statistical learning mechanisms and suggesting it operates on virtually any dimension the input is factorised. However, only linguistic duplets elicited a specific ERP component, potentially an N400 precursor, suggesting a lexical stage triggered by phonetic regularities already at birth. These results show that, from birth, multiple input regularities can be processed in parallel and feed different higher-order networks.