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

被引：11

作者：

Kim, Doyeon ^{[1
,2
]}

Jang, Sangwon ^{[1
]}

Kim, Jeongah ^{[1
]}

Park, Inah ^{[1
]}

Ku, Kyojin ^{[1
]}

Choi, Mijung ^{[1
]}

Lee, Sukwon ^{[3
]}

Heo, Won Do ^{[4
]}

Son, Gi Hoon ^{[5
]}

Choe, Han Kyoung ^{[1
]}

Kim, Kyungjin ^{[1
]}

机构：

[1] Daegu Gyeongbuk Inst Sci & Technol DGIST, Dept Brain & Cognit Sci, 333 Techno Jungang Daero, Daegu 42988, South Korea

[2] Seoul Natl Univ, Coll Nat Sci, Interdisciplinary Program Neurosci, Seoul, South Korea

[3] Korea Brain Res Inst, Dept Neural Dev & Dis, Daegu, South Korea

[4] Korea Adv Inst Sci & Technol KAIST, Dept Biol Sci, Daejeon, South Korea

[5] Korea Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea

来源：

NEUROENDOCRINOLOGY | 2020年 / 110卷 / 11-12期

基金：

新加坡国家研究基金会;

关键词：

Arcuate nucleus; Kisspeptin; Ca2+ oscillation; Synchronization; Neonate; NEUROKININ B; MEDIAN-EMINENCE; KISS1; NEURONS; OPTOGENETIC ACTIVATION; HORMONE SECRETION; CA2+ OSCILLATIONS; HIPPOCAMPAL CA1; TETANUS TOXIN; GNRH NEURONS; FEMALE;

D O I：

10.1159/000505922

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 ofKiss1-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. (c) 2020 The Author(s) Published by S. Karger AG, Basel

引用

页码：1010 / 1027

页数：18