Kisspeptin Neuron-Specific and Self-Sustained Calcium Oscillation in the Hypothalamic Arcuate Nucleus of Neonatal Mice: Regulatory Factors of its Synchronization
| Autor: | Doyeon Kim, Inah Park, Kyojin Ku, Han Kyoung Choe, Jeong Ah Kim, Sukwon Lee, Sangwon Jang, Mijung Choi, Gi Hoon Son, Won Do Heo, Kyungjin Kim |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Period (gene) Population Neuropeptide Mice Transgenic 030209 endocrinology & metabolism Neurotransmission Biology 030218 nuclear medicine & medical imaging Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Kisspeptin Arcuate nucleus Internal medicine medicine Animals Calcium Signaling education Neurons Kisspeptins education.field_of_study Endocrine and Autonomic Systems Sodium channel Arcuate Nucleus of Hypothalamus Ultradian Rhythm Cell biology medicine.anatomical_structure Animals Newborn Neuron hormones hormone substitutes and hormone antagonists Research Article |
| Zdroj: | Neuroendocrinology |
| ISSN: | 1423-0194 0028-3835 |
| DOI: | 10.1159/000505922 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|