PMID- 31611573
OWN - NLM
STAT- MEDLINE
DCOM- 20201030
LR  - 20220112
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Oct 14
TI  - Kisspeptin/Neurokinin B/Dynorphin (KNDy) cells as integrators of diverse internal 
      and external cues: evidence from viral-based monosynaptic tract-tracing in mice.
PG  - 14768
LID - 10.1038/s41598-019-51201-0 [doi]
LID - 14768
AB  - 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.
FAU - Moore, Aleisha M
AU  - Moore AM
AD  - Brain Health Research Institute and Dept. of Biological Sciences, Kent State 
      University, Kent, OH, USA. amoor149@kent.edu.
FAU - Coolen, Lique M
AU  - Coolen LM
AD  - Brain Health Research Institute and Dept. of Biological Sciences, Kent State 
      University, Kent, OH, USA.
FAU - Lehman, Michael N
AU  - Lehman MN
AD  - Brain Health Research Institute and Dept. of Biological Sciences, Kent State 
      University, Kent, OH, USA.
LA  - eng
GR  - K99 HD096120/HD/NICHD NIH HHS/United States
GR  - R01 HD039916/HD/NICHD NIH HHS/United States
GR  - K99HD096120/U.S. Department of Health & Human Services | NIH | Eunice Kennedy 
      Shriver National Institute of Child Health and Human Development 
      (NICHD)/International
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191014
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Kiss1 protein, mouse)
RN  - 0 (Kisspeptins)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 74913-18-1 (Dynorphins)
RN  - 86933-75-7 (Neurokinin B)
SB  - IM
MH  - Animals
MH  - Dynorphins/*metabolism
MH  - Female
MH  - Gonadotropin-Releasing Hormone/metabolism
MH  - Hypothalamus/cytology/*physiology
MH  - Kisspeptins/*metabolism
MH  - Male
MH  - Mice
MH  - Neurokinin B/*metabolism
MH  - Neurons/cytology/metabolism
MH  - Reproduction
MH  - Sex Characteristics
PMC - PMC6791851
COIS- The authors declare no competing interests.
EDAT- 2019/10/16 06:00
MHDA- 2020/10/31 06:00
PMCR- 2019/10/14
CRDT- 2019/10/16 06:00
PHST- 2019/07/05 00:00 [received]
PHST- 2019/09/25 00:00 [accepted]
PHST- 2019/10/16 06:00 [entrez]
PHST- 2019/10/16 06:00 [pubmed]
PHST- 2020/10/31 06:00 [medline]
PHST- 2019/10/14 00:00 [pmc-release]
AID - 10.1038/s41598-019-51201-0 [pii]
AID - 51201 [pii]
AID - 10.1038/s41598-019-51201-0 [doi]
PST - epublish
SO  - Sci Rep. 2019 Oct 14;9(1):14768. doi: 10.1038/s41598-019-51201-0.