Evoked transients of pH-sensitive fluorescent false neurotransmitter reveal dopamine hot spots in the globus pallidus

Abstract

Dopamine neurotransmission is suspected to play important physiological roles in multiple sparsely innervated brain nuclei, but there has not been a means to measure synaptic dopamine release in such regions. The globus pallidus externa (GPe) is a major locus in the basal ganglia that displays a sparse innervation of en passant dopamine axonal fibers. Due to the low levels of innervation that preclude electrochemical analysis, it is unknown if these axons engage in neurotransmission. To address this, we introduce an optical approach using a pH-sensitive fluorescent false neurotransmitter, FFN102, that exhibits increased fluorescence upon exocytosis from the acidic synaptic vesicle to the neutral extracellular milieu. In marked contrast to the striatum, FFN102 transients in the mouse GPe were spatially heterogeneous, smaller than in striatum with the exception of sparse hot spots, and significantly enhanced by high frequency stimulation. Our results support hot spots of dopamine release from substantia nigra axons.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jozsef Meszaros

    Laboratory for Functional Optical Imaging, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Timothy Cheung

    Department of Neurology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maya M Erler

    Graduate Program in Pharmacology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Un Jung Kang

    Department of Neurology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dalibor Sames

    Department of Chemistry, Columbia University, New York, United States
    For correspondence
    ds584@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
  6. Christoph Kellendonk

    Department of Psychiatry, Columbia University, New York, United States
    For correspondence
    ck491@cumc.columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3302-2188
  7. David Sulzer

    Department of Psychiatry, Columbia University, New York, United States
    For correspondence
    ds43@cumc.columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7632-0439

Funding

NIH Office of the Director (R01 NS101982)

  • Un Jung Kang
  • David Sulzer

U.S. Department of Defense (PR161817)

  • Un Jung Kang

Parkinson's Disease Foundation

  • Timothy Cheung
  • Un Jung Kang
  • David Sulzer

NARSAD

  • Christoph Kellendonk

JPB Foundation

  • David Sulzer

NIH Office of the Director (R01 DA07418)

  • David Sulzer

NIH Office of the Director (R03 NS096494)

  • Un Jung Kang

NIH Office of the Director (RO1 MH093672)

  • Christoph Kellendonk

NIH Office of the Director (T32 NS06492B-04)

  • Jozsef Meszaros

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

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Ethics

Animal experimentation: All animal protocols followed NIH guidelines and were approved by Columbia University's Institutional Animal Care and Use Committee.

Version history

  1. Received: October 9, 2018
  2. Accepted: December 18, 2018
  3. Accepted Manuscript published: December 19, 2018 (version 1)
  4. Version of Record published: January 8, 2019 (version 2)

Copyright

© 2018, Meszaros 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. Jozsef Meszaros
  2. Timothy Cheung
  3. Maya M Erler
  4. Un Jung Kang
  5. Dalibor Sames
  6. Christoph Kellendonk
  7. David Sulzer
(2018)
Evoked transients of pH-sensitive fluorescent false neurotransmitter reveal dopamine hot spots in the globus pallidus
eLife 7:e42383.
https://doi.org/10.7554/eLife.42383

Share this article

https://doi.org/10.7554/eLife.42383

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