Posterodorsal medial amygdala urocortin-3, GABA and glutamate mediate suppression of LH pulsatility in female mice
Posterodorsal medial amygdala urocortin-3, GABA and glutamate mediate suppression of LH pulsatility in female mice
复制标题
后背内侧杏仁核 urocortin-3、GABA 和谷氨酸介导雌性小鼠 LH 搏动的抑制
DOI：
10.1101/2022.07.07.499104
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ivanova D
中科院分区：
文献类型：
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作者：
Ivanova D
内侧杏仁核后背侧亚核（MePD）是下丘脑-垂体-性腺（HPG）和下丘脑-垂体-肾上腺（HPA）轴的上游调节器。抑制MePD urocortin-3（Ucn 3）神经元可防止心理应激诱导的黄体生成素（LH）脉动抑制，同时阻断应激诱导的雌性小鼠皮质酮（CORT）分泌升高。我们探讨的神经传递和神经回路抑制促性腺激素释放激素（GnRH）脉冲发生器的MePD Ucn 3神经元，我们进一步调查是否MePD Ucn 3传出投射下丘脑室旁核（PVN）控制CORT分泌和LH脉动。将Ucn 3-cre-td Tomato雌性卵巢切除（OVX）小鼠单侧注射腺相关病毒（AAV）-通道视紫红质2（ChR 2），并植入靶向MePD的光流体插管。我们用10 Hz的蓝光光学激活MePD中的Ucn 3神经元，并监测对LH脉冲的影响。接下来，我们将MePD Ucn 3神经元的光遗传学刺激与分别用荷包牡丹碱或CGP-35348以及NMDA和AMPA受体拮抗剂AP 5和CNQX的组合对GABA A或GABA B受体的药理学拮抗作用相结合，并观察对脉冲式LH分泌的影响。将具有17β-雌二醇替代物的Ucn 3-cre-tdTomato OVX小鼠的单独组在MePD中单侧注射AAV-ChR 2，并植入靶向PVN的光纤插管。我们用20 Hz的蓝光光学刺激PVN中的MePD Ucn 3传出投射，并监测对CORT分泌和LH脉冲的影响。我们首次揭示了MePD中Ucn 3神经元的激活通过MePD内的GABA和谷氨酸信号抑制GnRH脉冲发生器频率，而MePD Ucn 3投射到PVN调节HPG和HPA轴。
The posterodorsal subnucleus of the medial amygdala (MePD) is an upstream modulator of the hypothalamic–pituitary–gonadal (HPG) and hypothalamic–pituitary–adrenal (HPA) axes. Inhibition of MePD urocortin-3 (Ucn3) neurons prevents psychological stress–induced suppression of luteinizing hormone (LH) pulsatility while blocking the stress-induced elevations in corticosterone (CORT) secretion in female mice. We explore the neurotransmission and neural circuitry suppressing the gonadotropin-releasing hormone (GnRH) pulse generator by MePD Ucn3 neurons and we further investigate whether MePD Ucn3 efferent projections to the hypothalamic paraventricular nucleus (PVN) control CORT secretion and LH pulsatility. Ucn3-cre-tdTomato female ovariectomized (OVX) mice were unilaterally injected with adeno-associated virus (AAV)-channelrhodopsin 2 (ChR2) and implanted with optofluid cannulae targeting the MePD. We optically activated Ucn3 neurons in the MePD with blue light at 10 Hz and monitored the effect on LH pulses. Next, we combined optogenetic stimulation of MePD Ucn3 neurons with pharmacological antagonism of GABAAor GABABreceptors with bicuculline or CGP-35348, respectively, as well as a combination of NMDA and AMPA receptor antagonists, AP5 and CNQX, respectively, and observed the effect on pulsatile LH secretion. A separate group of Ucn3-cre-tdTomato OVX mice with 17β-estradiol replacement were unilaterally injected with AAV-ChR2 in the MePD and implanted with fiber-optic cannulae targeting the PVN. We optically stimulated the MePD Ucn3 efferent projections in the PVN with blue light at 20 Hz and monitored the effect on CORT secretion and LH pulses. We reveal for the first time that activation of Ucn3 neurons in the MePD inhibits GnRH pulse generator frequency via GABA and glutamate signaling within the MePD, while MePD Ucn3 projections to the PVN modulate the HPG and HPA axes.