Pedunculopontine glutamatergic neurons control spike patterning in substantia nigra dopaminergic neurons

  1. Daniel J Galtieri
  2. Chad M Estep
  3. David L Wokosin
  4. Stephen Traynelis
  5. D James Surmeier  Is a corresponding author
  1. Northwestern University, United States
  2. Emory University, United States

Abstract

Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches. These synapses were localized exclusively on the soma and proximal dendrites, placing them in a good location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc dopaminergic neurons. Moreover, burst stimulation of PPN axons was faithfully followed, even in the presence of NMDAR antagonists. Thus, PPN-evoked burst spiking of SNc dopaminergic neurons in vivo may not only be extrinsically triggered, but extrinsically patterned as well.

Article and author information

Author details

  1. Daniel J Galtieri

    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Chad M Estep

    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David L Wokosin

    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Stephen Traynelis

    Department of Pharmacology, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3750-9615
  5. D James Surmeier

    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    For correspondence
    j-surmeier@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6376-5225

Funding

JPB Foundation

  • Daniel J Galtieri
  • Chad M Estep
  • David L Wokosin
  • D James Surmeier

IDP Foundation

  • Daniel J Galtieri
  • Chad M Estep
  • David L Wokosin
  • D James Surmeier

National Institute of Neurological Disorders and Stroke

  • Daniel J Galtieri
  • Chad M Estep
  • David L Wokosin
  • D James Surmeier

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 experiments were performed in strict accordance with the guidelines set by the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were handled according to approved Institutional Animal Care and Use Committee protocols (IS00001185) of Northwestern University. All procedures were performed under isoflurane or ketamine/xylazine anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Rui M Costa, Columbia University in the City of New York, United States

Publication history

  1. Received: July 11, 2017
  2. Accepted: October 4, 2017
  3. Accepted Manuscript published: October 5, 2017 (version 1)
  4. Version of Record published: October 16, 2017 (version 2)

Copyright

© 2017, Galtieri 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. Daniel J Galtieri
  2. Chad M Estep
  3. David L Wokosin
  4. Stephen Traynelis
  5. D James Surmeier
(2017)
Pedunculopontine glutamatergic neurons control spike patterning in substantia nigra dopaminergic neurons
eLife 6:e30352.
https://doi.org/10.7554/eLife.30352

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