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Cited by 77Hypothalamic control of reproductive hormonesNeuroendocrine regulation and behaviorRegulation of Appetite and Obesity

Kisspeptin/Neurokinin B/Dynorphin (KNDy) cells as integrators of diverse internal and external cues: evidence from viral-based monosynaptic tract-tracing in mice

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Moore, Aleisha M., Coolen, Lique M., Lehman, Michael N.·2019·Scientific Reports
DOI 10.1038/s41598-019-51201-0PMC PMC6791851
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Abstract

Neurons in the hypothalamic arcuate nucleus (ARC) that co-express kisspeptin, neurokinin B and dynorphin (KNDy cells) are essential for mammalian reproduction as key regulators of gonadotropin-releasing hormone (GnRH) secretion. Although multiple endogenous and exogenous signals act indirectly via KNDy neurons to regulate GnRH, the identity of upstream neurons that provide synaptic input to this subpopulation is unclear. We used rabies-mediated tract-tracing in transgenic Kiss1-Cre mice combined with whole-brain optical clearing and multiple-label immunofluorescence to create a comprehensive and quantitative brain-wide map of neurons providing monosynaptic input to KNDy cells, as well as identify the estrogen receptor content and peptidergic phenotype of afferents. Over 90% of monosynaptic input to KNDy neurons originated from hypothalamic nuclei in both male and female mice. The greatest input arose from non-KNDy ARC neurons, including proopiomelanocortin-expressing cells. Significant female-dominant sex differences in afferent input were detected from estrogen-sensitive hypothalamic nuclei critical for reproductive endocrine function and sexual behavior in mice, indicating KNDy cells may provide a unique site for the coordination of sex-specific behavior and gonadotropin release. These data provide key insight into the structural framework underlying the ability of KNDy neurons to integrate endogenous and environmental signals important for the regulation of reproductive function.

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  • ARNKISS neurons integrate multiple internal homeostatic and external environmental cues to establish an appropriate pattern of pulsatile LH secretion for reproductive function.

    “Several lines of evidence indicate that ARNKISS neurons integrate multiple internal homeostatic and external environmental cues to establish an appropriate pattern of pulsatile LH secretion for reproductive function1,12–15.”

    From Brainstem noradrenergic modulation of the kisspeptin neuron GnRH pulse generator in mice (2025) · cites this paper as [15]

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Cited by

Sorted by citations

Authors
Moore, A. M., Coolen, L. M., & Lehman, M. N.
Affiliations
Kent State University (US)
Corresponding author
Moore, Aleisha M.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-10-14
Volume
9
Issue
1
Pages
14768-14768
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-51201-0
PMC
PMC6791851
OpenAlex
W2979308369
Cited by
77
References
16
Citations by year
2026: 2 · 2025: 9 · 2024: 18 · 2023: 13 · 2022: 14 · 2021: 10 · 2020: 10 · 2019: 1
FWCI
8.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • American Association of Anatomists (Postdoctoral Fellowship)
  • U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD096120)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
arcuate nucleus, hypothalamic neurons, proopiomelanocortin neurons, estrogen receptor, sex differences, gonadotropin-releasing hormone, reproductive endocrinology, synaptic integration
MeSH terms
Animals, Dynorphins, Female, Hypothalamus, Gonadotropin-Releasing Hormone, Male, Neurons, Reproduction, Sex Characteristics, Neurokinin B, Mice, Kisspeptins

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