Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females
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.
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
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.
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.
- Catherine Dulac, Harvard University, United States
- Received: February 3, 2018
- Accepted: July 24, 2018
- Accepted Manuscript published: August 6, 2018 (version 1)
- Version of Record published: August 21, 2018 (version 2)
© 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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