Forebrain projections of arcuate neurokinin B neurons demonstrated by anterograde tract-tracing and monosodium glutamate lesions in the rat
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Neurokinin B (NKB) and kisspeptin receptor signaling are essential components of the reproductive axis. A population of neurons resides within the arcuate nucleus of the rat that expresses NKB, kisspeptin, dynorphin, NK3 receptors and estrogen receptor alpha (ERalpha). Here we investigate the projections of these neurons using NKB-immunocytochemistry as a marker. First, the loss of NKB-immunoreactive (ir) somata and fibers was characterized after ablation of the arcuate nucleus by neonatal injections of monosodium glutamate. Second, biotinylated dextran amine was injected into the arcuate nucleus and anterogradely labeled NKB-ir fibers were identified using dual-labeled immunofluorescence. Four major projection pathways are described: (1) local projections within the arcuate nucleus bilaterally, (2) projections to the median eminence including the lateral palisade zone, (3) projections to a periventricular pathway extending rostrally to multiple hypothalamic nuclei, the septal region and BNST and dorsally to the dorsomedial nucleus and (4) Projections to a ventral hypothalamic tract to the lateral hypothalamus and medial forebrain bundle. The diverse projections provide evidence that NKB/kisspeptin/dynorphin neurons could integrate the reproductive axis with multiple homeostatic, behavioral and neuroendocrine processes. Interestingly, anterograde tract-tracing revealed NKB-ir axons originating from arcuate neurons terminating on other NKB-ir somata within the arcuate nucleus. Combined with previous studies, these experiments reveal a bilateral interconnected network of sex-steroid responsive neurons in the arcuate nucleus of the rat that express NKB, kisspeptin, dynorphin, NK3 receptors and ERalpha and project to GnRH terminals in the median eminence. This circuitry provides a mechanism for bilateral synchronization of arcuate NKB/kisspeptin/dynorphin neurons to modulate the pulsatile secretion of GnRH.
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KNDy neurons project to the MnPO and medial preoptic area.
“Our prediction that KNDy neurons project to preoptic regions that control heat dissipation effectors was correct, as demonstrated by KNDy neuron projections to the MnPO and medial preoptic area (Krajewski et al., 2010; Yeo and Herbison, 2011).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Krajewski et al., 2010
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References 85 · Cited by 178
- Authors
- Krajewski, S. J., Burke, M. C., Anderson, M. J., McMullen, N. T., & Rance, N. E.
- Affiliations
- University of Arizona (US)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 166
- Issue
- 2
- Pages
- 680-697
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2823949
- OpenAlex
- W2041506924
- Cited by
- 178
- References
- 85
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 15 · 2020: 7 · 2019: 9 · 2018: 10 · 2017: 12 · 2016: 10 · 2015: 12 · 2014: 20 · 2013: 21 · 2012: 21
- FWCI
- 17.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (U54-HD28-934, HD28934)
- National Institute on Aging (R01 AG-32315, R01 AG09214, R01AG009214, R01AG032315)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD028934, U54-HD-28934)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- neurokinin B, kisspeptin, arcuate nucleus, forebrain projections, dynorphin, NK3 receptor, estrogen receptor alpha, median eminence, hypothalamus, septal area, dorsomedial nucleus, lateral hypothalamus, medial forebrain bundle, reproductive axis
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Fluorescent Antibody Technique, Image Processing, Computer-Assisted, Median Eminence, Nerve Net, Neural Pathways, Neurons, Neurokinin B, Prosencephalon, Rats, Sprague-Dawley, Rats, Neuronal Tract-Tracers
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