Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females.
Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females.
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DOI：
10.7554/elife.35656
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发表时间：
2018-08-06
期刊：
影响因子：
7.7
通讯作者：
Rønnekleiv OK
中科院分区：
文献类型：
--
作者：
Qiu J;Rivera HM;Bosch MA;Padilla SL;Stincic TL;Palmiter RD;Kelly MJ;Rønnekleiv OK
下丘脑弓状核Kiss 1（Kiss 1ARH）神经元中的神经肽速激肽2（tachykinin 2，Tac 2）和kisspeptin（kisspeptin，Kiss 1）对GnRH的脉冲式释放和生殖是必需的。由于17β-雌二醇（17 β-estradiol，E2）降低Kiss 1ARH神经元Kiss 1和Tac 2 mRNA的表达，因此Kiss 1ARH神经元在E2驱动的促凋亡状态中的作用及其与POMC和NPY/AgRP摄食回路的协调作用在很大程度上被忽视。目前，我们发现，E2增强Kiss 1ARH神经元的兴奋性，通过放大Cacna 1g，Hcn 1和Hcn 2 mRNA的表达和T-型钙和h-电流。E2增加了Slc 17 a6 mRNA的表达和对弓状神经元的突触输入，通过代谢型受体兴奋POMC，抑制NPY/AgRP神经元。删除Slc 17 a6在Kiss 1神经元消除谷氨酸释放，并导致蔗糖在E2处理KO雌性小鼠的条件性位置偏好。因此，E2驱动的Kiss 1神经元兴奋性和谷氨酸神经传递的增加可能在女性可口食物的动机驱动中发挥关键作用。
The neuropeptides tachykinin2 (Tac2) and kisspeptin (Kiss1) in hypothalamic arcuate nucleus Kiss1 (Kiss1ARH) neurons are essential for pulsatile release of GnRH and reproduction. Since 17β-estradiol (E2) decreases Kiss1 and Tac2 mRNA expression in Kiss1ARH neurons, the role of Kiss1ARH neurons during E2-driven anorexigenic states and their coordination of POMC and NPY/AgRP feeding circuits have been largely ignored. Presently, we show that E2 augmented the excitability of Kiss1ARH neurons by amplifying Cacna1g, Hcn1 and Hcn2 mRNA expression and T-type calcium and h-currents. E2 increased Slc17a6 mRNA expression and glutamatergic synaptic input to arcuate neurons, which excited POMC and inhibited NPY/AgRP neurons via metabotropic receptors. Deleting Slc17a6 in Kiss1 neurons eliminated glutamate release and led to conditioned place preference for sucrose in E2-treated KO female mice. Therefore, the E2-driven increase in Kiss1 neuronal excitability and glutamate neurotransmission may play a key role in governing the motivational drive for palatable food in females.