PMID- 28938398
OWN - NLM
STAT- MEDLINE
DCOM- 20171016
LR  - 20181211
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 158
IP  - 10
DP  - 2017 Oct 1
TI  - Long-Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned 
      Activity That Is Modulated by Gonadal Steroids in Male Mice.
PG  - 3553-3564
LID - 10.1210/en.2017-00382 [doi]
AB  - Pulsatile release of gonadotropin-releasing hormone (GnRH) is key to fertility. 
      Pulse frequency is modulated by gonadal steroids and likely arises subsequent to 
      coordination of GnRH neuron firing activity. The source of rhythm generation and 
      the site of steroid feedback remain critical unanswered questions. Arcuate 
      neurons that synthesize kisspeptin, neurokinin B, and dynorphin (KNDy) may be 
      involved in both of these processes. We tested the hypotheses that action 
      potential firing in KNDy neurons is episodic and that gonadal steroids regulate 
      this pattern. Targeted extracellular recordings were made of green fluorescent 
      protein-identified KNDy neurons in brain slices from adult male mice that were 
      intact, castrated, or castrated and treated with estradiol or dihydrotestosterone 
      (DHT). KNDy neurons exhibited marked peaks and nadirs in action potential firing 
      activity during recordings lasting 1 to 3.5 hours. Peaks, identified by Cluster 
      analysis, occurred more frequently in castrated than intact mice, and either 
      estradiol or DHT in vivo or blocking neurokinin type 3 receptor in vitro restored 
      peak frequency to intact levels. The frequency of peaks in firing rate and 
      estradiol regulation of this frequency is similar to that observed for GnRH 
      neurons, whereas DHT suppressed firing in KNDy but not GnRH neurons. We further 
      examined the patterning of action potentials to identify bursts that may be 
      associated with increased neuromodulator release. Burst frequency and duration 
      are increased in castrated compared with intact and steroid-treated mice. The 
      observation that KNDy neurons fire in an episodic manner that is regulated by 
      steroid feedback is consistent with a role for these neurons in GnRH pulse 
      generation and regulation.
CI  - Copyright (c) 2017 Endocrine Society.
FAU - Vanacker, Charlotte
AU  - Vanacker C
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, Michigan 48109.
FAU - Moya, Manuel Ricu
AU  - Moya MR
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, Michigan 48109.
FAU - DeFazio, R Anthony
AU  - DeFazio RA
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, Michigan 48109.
FAU - Johnson, Michael L
AU  - Johnson ML
AD  - Department of Pharmacology, University of Virginia, Charlottesville, Virginia 
      22908.
FAU - Moenter, Suzanne M
AU  - Moenter SM
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, Michigan 48109.
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 
      48109.
AD  - Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, 
      Michigan 48109.
LA  - eng
GR  - R01 HD034860/HD/NICHD NIH HHS/United States
GR  - R37 HD034860/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Androgens)
RN  - 0 (Estrogens)
RN  - 0 (Kiss1 protein, mouse)
RN  - 0 (Kisspeptins)
RN  - 0 (Receptors, Neurokinin-3)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 4TI98Z838E (Estradiol)
RN  - 74913-18-1 (Dynorphins)
RN  - 86933-75-7 (Neurokinin B)
SB  - IM
MH  - Action Potentials/*drug effects/physiology
MH  - Androgens/*pharmacology
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus/*cytology
MH  - Brain/drug effects/metabolism/physiology
MH  - Cluster Analysis
MH  - Dihydrotestosterone/*pharmacology
MH  - Dynorphins/metabolism
MH  - Estradiol/*pharmacology
MH  - Estrogens/*pharmacology
MH  - Gonadotropin-Releasing Hormone/metabolism
MH  - Green Fluorescent Proteins/genetics
MH  - Kisspeptins/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Neurokinin B/metabolism
MH  - Neurons/*drug effects/metabolism/physiology
MH  - *Orchiectomy
MH  - Patch-Clamp Techniques
MH  - Receptors, Neurokinin-3/antagonists & inhibitors
PMC - PMC5659697
EDAT- 2017/09/25 06:00
MHDA- 2017/10/17 06:00
PMCR- 2018/10/01
CRDT- 2017/09/23 06:00
PHST- 2017/04/19 00:00 [received]
PHST- 2017/07/25 00:00 [accepted]
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2017/10/17 06:00 [medline]
PHST- 2017/09/23 06:00 [entrez]
PHST- 2018/10/01 00:00 [pmc-release]
AID - 4049500 [pii]
AID - endo_201700382 [pii]
AID - 10.1210/en.2017-00382 [doi]
PST - ppublish
SO  - Endocrinology. 2017 Oct 1;158(10):3553-3564. doi: 10.1210/en.2017-00382.