Han Su Young, Morris Paul G, Kim Jae-Chang, Guru Santosh, Pardo-Navarro Maria, Yeo Shel-Hwa, McQuillan H James, Herbison Allan E
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Zurich Centre for Neuroeconomics, Department of Economics, University of Zurich, 8006 Zurich, Switzerland.
Cell Rep. 2023 Jan 31;42(1):111914. doi: 10.1016/j.celrep.2022.111914. Epub 2023 Jan 2.
The mechanism by which arcuate nucleus kisspeptin (ARN) neurons co-expressing glutamate, neurokinin B, and dynorphin intermittently synchronize their activity to generate pulsatile hormone secretion remains unknown. An acute brain slice preparation maintaining synchronized ARN neuron burst firing was used alongside in vivo GCaMP GRIN lens microendoscope and fiber photometry imaging coupled with intra-ARN microinfusion. Studies in intact and gonadectomized male mice revealed that ARN neuron synchronizations result from near-random emergent network activity within the population and that this was critically dependent on local glutamate-AMPA signaling. Whereas neurokinin B operated to potentiate glutamate-generated synchronizations, dynorphin-kappa opioid tone within the network served as a gate for synchronization initiation. These observations force a departure from the existing "KNDy hypothesis" for ARN neuron synchronization. A "glutamate two-transition" mechanism is proposed to underlie synchronizations in this key hypothalamic central pattern generator driving mammalian fertility.
弓状核吻素（ARN）神经元共表达谷氨酸、神经激肽B和强啡肽，其活动间歇性同步以产生脉冲式激素分泌的机制尚不清楚。利用一种能维持ARN神经元同步爆发放电的急性脑片制备方法，同时结合体内GCaMP GRIN透镜微内窥镜和纤维光度成像以及ARN内微量注射。对完整和去势雄性小鼠的研究表明，ARN神经元同步是由群体内近乎随机出现的网络活动导致的，且这严重依赖于局部谷氨酸-AMPA信号传导。虽然神经激肽B起到增强谷氨酸产生的同步作用，但网络内的强啡肽-κ阿片样物质张力作为同步启动的闸门。这些观察结果迫使人们背离现有的关于ARN神经元同步的“KNDy假说”。本文提出一种“谷氨酸双转变”机制，作为驱动哺乳动物生育能力的这个关键下丘脑中央模式发生器同步的基础。
