Evidence map›Paper›PMID 27093227›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2016

Optogenetic Stimulation of Arcuate Nucleus Kiss1 Neurons Reveals a Steroid-Dependent Glutamatergic Input to POMC and AgRP Neurons in Male Mice.

Casey C Nestor, Jian Qiu, Stephanie L Padilla, Chunguang Zhang, Martha A Bosch, Wei Fan, Sue A Aicher, Richard D Palmiter, Oline K Rønnekleiv, Martin J Kelly

Open access · bronzeAbstract read
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
16.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Effects of menopause on temperature regulation.Temperature (Austin, Tex.) · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Obesity Alters POMC and Kisspeptin Neuron Cross Talk Leading to Reduced Luteinizing Hormone in Male Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  13. Article
  14. Review
  15. Store-operated CaPNAS nexus · 2023
    Article
  16. Article
  17. Modelling KNDy neurons and gonadotropin-releasing hormone pulse generation.Current opinion in endocrine and metabolic research · 2022
    Review
  18. Review
  19. Article
  20. Review

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Casey C NestorDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Jian QiuDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Stephanie L PadillaDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Chunguang ZhangDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Martha A BoschDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Wei FanDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Sue A AicherDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Richard D PalmiterDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Oline K RønnekleivDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Martin J KellyDepartment of Physiology and Pharmacology (C.CN., J.Q., C.Z., M.A.B., S.A.A., O.K.R., M.J.K.) and Anesthesiology and Perioperative Medicine and Knight Cardiovascular Institute (W.F.), Oregon Health & Science University, Portland, Oregon 97239; Division of Neuroscience (O.K.R., M.J.K.), Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006; and Howard Hughes Medical Institute (S.L.P., R.D.P.), University of Washington, Seattle, Washington 98195.
Oregon Health & Science University · USHoward Hughes Medical Institute · USOregon National Primate Research Center · US

Funding

Sex Differences in the Control of FeedingR01DK068098 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI KELLY, MARTIN JEFFREY, RØNNEKLEIV, OLINE KARIN · 2005 to 2024
$7.1M
MULTIDISCIPLINARY TRAINING IN NEUROENDOCRINOLOGYT32DK007680 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI GOODMAN, RICHARD H. · 1991 to 2015
$6.8M
BETA ENDORPHIN NEURONS AND THE CONTROL OF HOMEOSTASISR01NS038809 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI KELLY, MARTIN JEFFREY · 1999 to 2018
$6.8M
Ultrastructure and Single Particle Microscopy CoreP30NS061800 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI AICHER, SUE A · 2009 to 2020
$6.6M
Estrogen Modulation of Bursting Activity in GnRH NeuronsR01NS043330 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI RØNNEKLEIV, OLINE KARIN · 2004 to 2019
$5.5M
Effect of Killing or Removing GABA from NPY/AgRP NeuronsR01DA024908 · NIDA · UNIVERSITY OF WASHINGTON · PI PALMITER, RICHARD D. · 2007 to 2021
$3.5M
Regulation of Thermogenesis by the Melanocortin SystemR01DK062179 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI FAN, WEI · 2003 to 2011
$2.5M
REPRODUCTIVE BIOLOGY--MULTIDISCIPLINARYT32HD007133 · NICHD · OREGON HEALTH & SCIENCE UNIVERSITY · PI ROSELLI, CHARLES E. · 1985 to 2014
$2.2M
Kisspeptin Synaptic Input to POMC NeuronsF32DK103446 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI NESTOR, CASEY C · 2014 to 2014
$53k
NICHD NIH HHS T32 HD007133NIDA NIH HHS R01 DA024908NIDDK NIH HHS F32 DK103446NIDDK NIH HHS R01 DK062179NIDDK NIH HHS R01 DK068098NIDDK NIH HHS T32 DK007680NINDS NIH HHS P30 NS061800NINDS NIH HHS R01 NS038809NINDS NIH HHS R01 NS043330
6 · The paper itself

Abstract

Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. Proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, located in the arcuate nucleus (ARC) of the hypothalamus, integrate numerous excitatory and inhibitory inputs to ultimately regulate energy homeostasis. Given that POMC and AgRP neurons are contacted by Kiss1 neurons in the ARC (Kiss1(ARC)) and they express androgen receptors, Kiss1(ARC) neurons may mediate the orexigenic action of testosterone via POMC and/or AgRP neurons. Quantitative PCR analysis of pooled Kiss1(ARC) neurons revealed that mRNA levels for Kiss1 and vesicular glutamate transporter 2 were higher in castrated male mice compared with gonad-intact males. Single-cell RT-PCR analysis of yellow fluorescent protein (YFP) ARC neurons harvested from males injected with AAV1-EF1α-DIO-ChR2:YFP revealed that 100% and 88% expressed mRNAs for Kiss1 and vesicular glutamate transporter 2, respectively. Whole-cell, voltage-clamp recordings from nonfluorescent postsynaptic ARC neurons showed that low frequency photo-stimulation (0.5 Hz) of Kiss1-ChR2:YFP neurons elicited a fast glutamatergic inward current in POMC and AgRP neurons. Paired-pulse, photo-stimulation revealed paired-pulse depression, which is indicative of greater glutamate release, in the castrated male mice compared with gonad-intact male mice. Group I and group II metabotropic glutamate receptor agonists depolarized and hyperpolarized POMC and AgRP neurons, respectively, which was mimicked by high frequency photo-stimulation (20 Hz) of Kiss1(ARC) neurons. Therefore, POMC and AgRP neurons receive direct steroid- and frequency-dependent glutamatergic synaptic input from Kiss1(ARC) neurons in male mice, which may be a critical pathway for Kiss1 neurons to help coordinate energy homeostasis and reproduction.

Indexed as

OptogeneticsAction PotentialsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusAxonsCastrationChannelrhodopsinsgamma-Aminobutyric AcidGlutamatesKisspeptinsLightMaleMice, Inbred C57BLNeuronsPro-OpiomelanocortinAgouti-Related ProteinChannelrhodopsinsgamma-Aminobutyric AcidGlutamatesKisspeptinsmetabotropic glutamate receptor 2Pro-OpiomelanocortinReceptors, Metabotropic GlutamateRNA, MessengerSteroidsVesicular Glutamate Transport Protein 2

Identifiers

PMID27093227
PMCPMC4884339
OpenAlexW2340417327

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.