Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

  1. Stephanie C Gantz
  2. Brooks G Robinson
  3. David C Buck
  4. James R Bunzow
  5. Rachael L Neve
  6. John T Williams
  7. Kim A Neve  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. Oregon Health & Science University, United States
  3. United States Department of Veterans Affairs, United States
  4. Massachusetts Institute of Technology, United States

Abstract

D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent GIRK currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors.

Article and author information

Author details

  1. Stephanie C Gantz

    Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Brooks G Robinson

    Vollum Institute, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David C Buck

    Research Service, VA Portland Health Care System, United States Department of Veterans Affairs, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. James R Bunzow

    Vollum Institute, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rachael L Neve

    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. John T Williams

    Vollum Institute, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kim A Neve

    Research Service, VA Portland Health Care System, United States Department of Veterans Affairs, Portland, United States
    For correspondence
    nevek@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All studies were conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and were approved by the Institutional Animal Care and Use Committees at the VA Portland Health Care System (#2577-12) and Oregon Health & Science University (IS01394).

Reviewing Editor

  1. Sacha B Nelson, Brandeis University, United States

Publication history

  1. Received: June 11, 2015
  2. Accepted: August 25, 2015
  3. Accepted Manuscript published: August 26, 2015 (version 1)
  4. Version of Record published: September 21, 2015 (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.

Metrics

  • 2,877
    Page views
  • 523
    Downloads
  • 33
    Citations

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

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. Stephanie C Gantz
  2. Brooks G Robinson
  3. David C Buck
  4. James R Bunzow
  5. Rachael L Neve
  6. John T Williams
  7. Kim A Neve
(2015)
Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium
eLife 4:e09358.
https://doi.org/10.7554/eLife.09358
  1. Further reading

Further reading

    1. Neuroscience
    Yiya Chen, Yige Gao ... Jiawei Zhou
    Research Article

    The adult human visual system maintains the ability to be altered by sensory deprivation. What has not been considered is whether the internal neural states modulate visual sensitivity to short-term monocular deprivation. In this study we manipulated the internal neural state and reported changes in intrinsic neural oscillations with a patched eye open or closed. We investigated the influence of eye open/eye closure on the unpatched eye's contrast sensitivity and ocular dominance (OD) shifts induced by short-term monocular deprivation. The results demonstrate that internal neural states influence not only baseline contrast sensitivity but also the extent to which the adult visual system can undergo changes in ocular dominance.

    1. Neuroscience
    2. Physics of Living Systems
    Sabrina A Jones, Jacob H Barfield ... Woodrow L Shew
    Research Article

    Naturally occurring body movements and collective neural activity both exhibit complex dynamics, often with scale-free, fractal spatiotemporal structure. Scale-free dynamics of both brain and behavior are important because each is associated with functional benefits to the organism. Despite their similarities, scale-free brain activity and scale-free behavior have been studied separately, without a unified explanation. Here we show that scale-free dynamics of mouse behavior and neurons in visual cortex are strongly related. Surprisingly, the scale-free neural activity is limited to specific subsets of neurons, and these scale-free subsets exhibit stochastic winner-take-all competition with other neural subsets. This observation is inconsistent with prevailing theories of scale-free dynamics in neural systems, which stem from the criticality hypothesis. We develop a computational model which incorporates known cell-type-specific circuit structure, explaining our findings with a new type of critical dynamics. Our results establish neural underpinnings of scale-free behavior and clear behavioral relevance of scale-free neural activity.