Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females

  1. Jian Qiu
  2. Heidi M Rivera
  3. Martha A Bosch
  4. Stephanie L Padilla
  5. Todd L Stincic
  6. Richard D Palmiter
  7. Martin J Kelly
  8. Oline K Rønnekleiv  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. Howard Hughes Medical Institute, University of Washington, United States

Abstract

The neuropeptides tachykinin2 (Tac2) and kisspeptin (Kiss1) in hypothalamic arcuate nucleus Kiss1 (Kiss1ARH) neurons are essential for pulsatile release of GnRH and reproduction. Since 17β-estradiol (E2) decreases Kiss1 and Tac2 mRNA expression in Kiss1ARH neurons, the role of Kiss1ARH neurons during E2-driven anorexigenic states and their coordination of POMC and NPY/AgRP feeding circuits have been largely ignored. Presently, we show that E2 augmented the excitability of Kiss1ARH neurons by amplifying Cacna1g, Hcn1 and Hcn2 mRNA expression and T-type calcium and h-currents. E2 increased Slc17a6 mRNA expression and glutamatergic synaptic input to arcuate neurons, which excited POMC and inhibited NPY/AgRP neurons via metabotropic receptors. Deleting Slc17a6 in Kiss1 neurons eliminated glutamate release and led to conditioned place preference for sucrose in E2-treated KO female mice. Therefore, the E2-driven increase in Kiss1 neuronal excitability and glutamate neurotransmission may play a key role in governing the motivational drive for palatable food in females.

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. Jian Qiu

    Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4988-8587
  2. Heidi M Rivera

    Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
    Competing interests
    No competing interests declared.
  3. Martha A Bosch

    Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
    Competing interests
    No competing interests declared.
  4. Stephanie L Padilla

    Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  5. Todd L Stincic

    Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
    Competing interests
    No competing interests declared.
  6. Richard D Palmiter

    Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, United States
    Competing interests
    Richard D Palmiter, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6587-0582
  7. Martin J Kelly

    Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8633-2510
  8. Oline K Rønnekleiv

    Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, United States
    For correspondence
    ronnekle@ohsu.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1841-4386

Funding

National Institutes of Health (R01-DK068098)

  • Martin J Kelly
  • Oline K Rønnekleiv

National Institutes of Health (R01-NS043330)

  • Oline K Rønnekleiv

National Institutes of Health (R01-NS038809)

  • Martin J Kelly

National Institutes of Health (R01-DA024908)

  • Richard D Palmiter

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

Reviewing Editor

  1. Catherine Dulac, Harvard University, United States

Ethics

Animal experimentation: Animal experimentation: This study was performed in strict accordance with the recommendations from the National Institutes of Health Guide for the care and use of Laboratory Animals. All animal procedures were conducted according to the approved institutional animal care and use committee (IACUC) protocols (#IP00000585; #IP00000382) at Oregon health and Science University and (#2183-02) at University of Washington. All surgeries were performed using aseptic techniques under isoflurane anesthesia, and every effort was made to minimize suffering.

Version history

  1. Received: February 3, 2018
  2. Accepted: July 24, 2018
  3. Accepted Manuscript published: August 6, 2018 (version 1)
  4. Version of Record published: August 21, 2018 (version 2)

Copyright

© 2018, Qiu 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. Jian Qiu
  2. Heidi M Rivera
  3. Martha A Bosch
  4. Stephanie L Padilla
  5. Todd L Stincic
  6. Richard D Palmiter
  7. Martin J Kelly
  8. Oline K Rønnekleiv
(2018)
Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females
eLife 7:e35656.
https://doi.org/10.7554/eLife.35656

Share this article

https://doi.org/10.7554/eLife.35656

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