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.

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.

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.

Metrics

  • 2,602
    views
  • 546
    downloads
  • 85
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. 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

Further reading

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.

    1. Neuroscience
    Sven Ohl, Martin Rolfs
    Research Article

    Detecting causal relations structures our perception of events in the world. Here, we determined for visual interactions whether generalized (i.e. feature-invariant) or specialized (i.e. feature-selective) visual routines underlie the perception of causality. To this end, we applied a visual adaptation protocol to assess the adaptability of specific features in classical launching events of simple geometric shapes. We asked observers to report whether they observed a launch or a pass in ambiguous test events (i.e. the overlap between two discs varied from trial to trial). After prolonged exposure to causal launch events (the adaptor) defined by a particular set of features (i.e. a particular motion direction, motion speed, or feature conjunction), observers were less likely to see causal launches in subsequent ambiguous test events than before adaptation. Crucially, adaptation was contingent on the causal impression in launches as demonstrated by a lack of adaptation in non-causal control events. We assessed whether this negative aftereffect transfers to test events with a new set of feature values that were not presented during adaptation. Processing in specialized (as opposed to generalized) visual routines predicts that the transfer of visual adaptation depends on the feature similarity of the adaptor and the test event. We show that the negative aftereffects do not transfer to unadapted launch directions but do transfer to launch events of different speeds. Finally, we used colored discs to assign distinct feature-based identities to the launching and the launched stimulus. We found that the adaptation transferred across colors if the test event had the same motion direction as the adaptor. In summary, visual adaptation allowed us to carve out a visual feature space underlying the perception of causality and revealed specialized visual routines that are tuned to a launch’s motion direction.