Estrogen permits vasopressin signaling in preoptic kisspeptin neurons in the female mouse.
The cellular mechanisms governing the impact of the central circadian clock on neuronal networks are incompletely understood. We examine here the influence of the suprachiasmatic nucleus output neuropeptide arginine-vasopressin (AVP) on the activity of preoptic area kisspeptin neurons. These cells integrate circadian and hormonal signals within the neuronal network that regulates fertility in females. Electrophysiological recordings in brain slices from kisspeptin-GFP mice showed that AVP dose-dependently increased the firing rate of most kisspeptin neurons. These actions were mediated directly at the kisspeptin neuron. Experiments in mice expressing the calcium indicator GCaMP3 in kisspeptin neurons enabled simultaneous monitoring of intracellular calcium concentrations ([Ca(2+)]i) in multiple cells and revealed that AVP increased [Ca(2+)]i in >80% of diestrous kisspeptin neurons via a mechanism involving voltage-gated calcium channels. We next examined whether AVP signaling in kisspeptin neurons was time and ovarian cycle dependent. AVP exerted the same effects on diestrous and proestrous days of the ovarian cycle, whether hours before [zeitgeber time 4 (ZT4)-ZT6] or just before (ZT10) the expected time of the proestrous preovulatory luteinizing hormone surge. Remarkably, however, AVP signaling was critically dependent on circulating ovarian steroids as AVP no longer excited preoptic kisspeptin neurons in ovariectomized mice, an effect that was fully restored by estradiol treatment. Together, these studies show that AVP exerts a potent and direct stimulatory influence upon the electrical activity and [Ca(2+)]i of most preoptic kisspeptin neurons. Unexpectedly, estrogen is found to permit circadian AVP signaling at preoptic kisspeptin neurons rather than dynamically modulate its activity throughout the estrous cycle.
Centre for Neuroendocrinology and Department of Physiology, Otago School of Medical Sciences, University of Otago, 9054 Dunedin, New Zealand, and.
Richard
http://orcid.org/0000-0001-5160-6027
R
Piet
Centre for Neuroendocrinology and Department of Physiology, Otago School of Medical Sciences, University of Otago, 9054 Dunedin, New Zealand, and.
Antoine
A
Fraissenon
Department of Pharmacology and Toxicology, University of Saarland School of Medicine, D-66421 Homburg, Germany.
Ulrich
U
Boehm
Centre for Neuroendocrinology and Department of Physiology, Otago School of Medical Sciences, University of Otago, 9054 Dunedin, New Zealand, and allan.herbison@otago.ac.nz.
Allan E
http://orcid.org/0000-0002-9615-3022
AE
Herbison
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D030801:Animals, Genetically Modified; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D030762:Estrous Cycle / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D010052:Ovariectomy; D011301:Preoptic Area / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000166:cytology; D013779:Tetrodotoxin / Q000494:pharmacology
D004967:Estrogens; D018691:Excitatory Amino Acid Antagonists; D059648:Kisspeptins; D026941:Sodium Channel Blockers; D001127:Arginine Vasopressin; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D002118:Calcium
GnRH; circadian system; ovarian steroids; ovulation