Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron

  1. Xinhuai Liu
  2. Shel-Hwa Yeo
  3. H James McQuillan
  4. Michel K Herde
  5. Sabine Hessler
  6. Isaiah Cheong
  7. Robert Porteous
  8. Allan Edward Herbison  Is a corresponding author
  1. University of Otago, New Zealand
  2. University of Cambridge, United Kingdom

Abstract

The necessity and functional significance of neurotransmitter co-transmission remains unclear. The glutamatergic 'KNDy' neurons co-express kisspeptin, neurokinin B (NKB) and dynorphin and exhibit a highly stereotyped synchronized behavior that reads out to the gonadotropin-releasing hormone (GnRH) neuron dendrons to drive episodic hormone secretion. Using expansion microscopy, we show that KNDy neurons make abundant close, non-synaptic appositions with the GnRH neuron dendron. Electrophysiology and confocal GCaMP6 imaging demonstrated that, despite all three neuropeptides being released from KNDy terminals, only kisspeptin was able to activate the GnRH neuron dendron. Mice with a selective deletion of kisspeptin from KNDy neurons failed to exhibit pulsatile hormone secretion but maintained synchronized episodic KNDy neuron behavior thought to depend on recurrent NKB and dynorphin transmission. This indicates that KNDy neurons drive episodic hormone secretion through highly redundant neuropeptide co-transmission orchestrated by differential postsynaptic neuropeptide receptor expression at the GnRH neuron dendron and KNDy neuron.

Data availability

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

Article and author information

Author details

  1. Xinhuai Liu

    Physiology, University of Otago, Dunedin, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  2. Shel-Hwa Yeo

    Physiology, Development & Neuroscience, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. H James McQuillan

    Physiology, University of Otago, Dunedin, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  4. Michel K Herde

    Physiology, University of Otago, Dunedin, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2324-2083
  5. Sabine Hessler

    Physiology, University of Otago, Dunedin, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4177-4825
  6. Isaiah Cheong

    Centre for Neuroendocrinology, Department of Physiology, University of Otago, Dunedin, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  7. Robert Porteous

    Physiology, University of Otago, Dunedin, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  8. Allan Edward Herbison

    Physiology, Development & Neuroscience, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    aeh36@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9615-3022

Funding

New Zealand Health Research Council

  • Allan Edward Herbison

Wellcome Trust

  • Allan Edward Herbison

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 handling and experimental protocols were undertaken as approved by the Animal Welfare Ethics Committees of the University of Otago, New Zealand (96/2017) or the University of Cambridge, UK (P174441DE).

Reviewing Editor

  1. Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States

Version history

  1. Received: August 26, 2020
  2. Accepted: January 15, 2021
  3. Accepted Manuscript published: January 19, 2021 (version 1)
  4. Version of Record published: January 29, 2021 (version 2)

Copyright

© 2021, Liu 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. Xinhuai Liu
  2. Shel-Hwa Yeo
  3. H James McQuillan
  4. Michel K Herde
  5. Sabine Hessler
  6. Isaiah Cheong
  7. Robert Porteous
  8. Allan Edward Herbison
(2021)
Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron
eLife 10:e62455.
https://doi.org/10.7554/eLife.62455

Share this article

https://doi.org/10.7554/eLife.62455

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