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Kisspeptin Neuron-Specific and Self-Sustained Calcium Oscillation in the Hypothalamic Arcuate Nucleus of Neonatal Mice: Regulatory Factors of its Synchronization

Title
Kisspeptin Neuron-Specific and Self-Sustained Calcium Oscillation in the Hypothalamic Arcuate Nucleus of Neonatal Mice: Regulatory Factors of its Synchronization
Authors
Kim, DoyeonJang, SangwonKim, JeongahPark, InahKu, KyojinChoi, MijungLee, SukwonHeo, Won DoSon, Gi HoonChoe, Han KyoungKim, Kyungjin
DGIST Authors
Choe, Han Kyoung
Issue Date
2020-10
Citation
Neuroendocrinology, 110(11-12), 1010-1027
Type
Article
Article Type
Article
Author Keywords
SynchronizationNeonateArcuate nucleusKisspeptinCa2+ oscillation
Keywords
NEUROKININ BMEDIAN-EMINENCEKISS1 NEURONSOPTOGENETIC ACTIVATIONHORMONE SECRETIONCA2+ OSCILLATIONSHIPPOCAMPAL CA1TETANUS TOXINGNRH NEURONSFEMALE
ISSN
0028-3835
Abstract
Introduction: Synchronous and pulsatile neural activation of kisspeptin neurons in the arcuate nucleus (ARN) are important components of the gonadotropin-releasing hormone pulse generator, the final common pathway for central regulation of mammalian reproduction. However, whether ARN kisspeptin neurons can intrinsically generate self-sustained synchronous oscillations from the early neonatal period and how they are regulated remain unclear. Objective: This study aimed to examine the endogenous rhythmicity of ARN kisspeptin neurons and its neural regulation using a neonatal organotypic slice culture model. Methods: We monitored calcium (Ca2+) dynamics in real-time from individual ARN kisspeptin neurons in neonatal organotypic explant cultures of Kiss1-IRES-Cre mice transduced with genetically encoded Ca2+ indicators. Pharmacological approaches were employed to determine the regulations of kisspeptin neuron-specific Ca2+ oscillations. A chemogenetic approach was utilized to assess the contribution of ARN kisspeptin neurons to the population dynamics. Results: ARN kisspeptin neurons in neonatal organotypic cultures exhibited a robust synchronized Ca2+ oscillation with a period of approximately 3 min. Kisspeptin neuron-specific Ca2+ oscillations were dependent on voltage-gated sodium channels and regulated by endoplasmic reticulum-dependent Ca2+ homeostasis. Chemogenetic inhibition of kisspeptin neurons abolished synchronous Ca2+ oscillations, but the autocrine actions of the neuropeptides were marginally effective. Finally, neonatal ARN kisspeptin neurons were regulated by N-methyl-D-aspartate and gamma-aminobutyric acid receptor-mediated neurotransmission. Conclusion: These data demonstrate that ARN kisspeptin neurons in organotypic cultures can generate synchronized and self-sustained Ca2+ oscillations. These oscillations controlled by multiple regulators within the ARN are a novel ultradian rhythm generator that is active during the early neonatal period. © 2020 S. Karger AG. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/12576
DOI
10.1159/000505922
Publisher
S. Karger AG
Related Researcher
  • Author Choe, Han Kyoung Laboratory of Animal Behavior and Circadian rhythm
  • Research Interests Modulation of neural circuit; Circadian regulation of behavior and perception; Neurotechnology
Files:
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Collection:
Department of Brain and Cognitive SciencesLaboratory of Animal Behavior and Circadian rhythm1. Journal Articles


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