GnRH pulse generator frequency is modulated by kisspeptin and GABA-glutamate interactions in the posterodorsal medial amygdala in female mice.
GnRH pulse generator frequency is modulated by kisspeptin and GABA-glutamate interactions in the posterodorsal medial amygdala in female mice.
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DOI：
10.1111/jne.13207
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发表时间：
2022-11
影响因子：
3.2
通讯作者：
O'Byrne, Kevin T.
中科院分区：
文献类型：
--
作者：
Lass, Geffen;Li, Xiao Feng;Voliotis, Margaritis;Wall, Ellen;de Burgh, Ross A.;Ivanova, Deyana;McIntyre, Caitlin;Lin, Xian-Hua;Colledge, William H.;Lightman, Stafford L.;Tsaneva-Atanasova, Krasimira;O'Byrne, Kevin T.
下丘脑弓状核中的Kisspeptin神经元产生促性腺激素释放激素（GnRH）脉冲，并作为功能性促性腺激素分泌和生殖能力的关键启动子。然而，kisspeptin在其他脑区，最值得注意的是内侧杏仁核（MePD）的后背亚核，对下丘脑kisspeptin群体起着重要的调节作用;我们最近使用光遗传学的研究表明，低频光刺激MePD kisspeptin导致黄体生成素脉冲频率增加。尽管如此，支持这种调节功能的神经化学途径仍然未知。为了研究这一点，我们利用了一种光流体技术，将光遗传学刺激与核内药理学受体拮抗作用精确地结合起来，以研究这种回路中涉及的神经传递。我们已经证明实验和验证使用的数学模型，GABA和谷氨酸的功能性神经传递是有效调制的GnRH脉冲发生器的杏仁核kisspeptin神经元的要求。模拟杏仁核上游调节下丘脑GnRH脉冲发生器（ARC KNDy网络）。(A)MePD Kiss 1神经元的光遗传刺激（a）激活GABA-GABA去抑制通路（B），降低MePD引起的抑制性GABA能紧张（c），以及激活投射到GABA能传出神经的多巴胺能中间神经元（d），抵消MePD的刺激输出（e），以加速GnRH脉冲发生器频率。(B)光刺激MePD Kiss 1后，MePD中GABA受体拮抗作用导致KNDy网络的净抑制，从而降低脉冲频率。(C)MePD Kiss 1的光刺激谷氨酸受体拮抗作用过度刺激KNDy网络，导致GnRH脉冲发生器从脉动状态转变为静态动态状态。
Kisspeptin neurons in the arcuate nucleus of the hypothalamus generate gonadotrophin‐releasing hormone (GnRH) pulses, and act as critical initiators of functional gonadotrophin secretion and reproductive competency. However, kisspeptin in other brain regions, most notably the posterodorsal subnucleus of the medial amygdala (MePD), plays a significant modulatory role over the hypothalamic kisspeptin population; our recent studies using optogenetics have shown that low‐frequency light stimulation of MePD kisspeptin results in increased luteinsing hormone pulse frequency. Nonetheless, the neurochemical pathways that underpin this regulatory function remain unknown. To study this, we have utilised an optofluid technology, precisely combining optogenetic stimulation with intra‐nuclear pharmacological receptor antagonism, to investigate the neurotransmission involved in this circuitry. We have shown experimentally and verified using a mathematical model that functional neurotransmission of both GABA and glutamate is a requirement for effective modulation of the GnRH pulse generator by amygdala kisspeptin neurons. Modelling amygdala upstream regulation of the hypothalamic GnRH pulse generator (ARC KNDy network). (A), Optogenetic stimulation (a) of MePD Kiss1 neurones activates the GABA‐GABA disinhibitory pathway (b) reducing the inhibitory GABAergic tone arising from the MePD (c), as well as activating glutamatergic interneurones (d) projecting to the GABAergic efferents, counteracting the stimulatory output of the MePD (e) to accelerate GnRH pulse generator frequency. (B), GABA receptor antagonism in the MePD with optical stimulation of MePD Kiss1, results in net inhibition of the KNDy network to decrease pulse frequency. (C), Glutamate receptor antagonism with optical stimulation of MePD Kiss1, over‐stimulates the KNDy network resulting in a transition from a pulsatile to a quiescent dynamic state of the GnRH pulse generator.
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影响因子：
7.7
作者：
Qiu J;Rivera HM;Bosch MA;Padilla SL;Stincic TL;Palmiter RD;Kelly MJ;Rønnekleiv OK
通讯作者：
Rønnekleiv OK
影响因子：
3.7
作者：
Comninos AN;Yang L;O'Callaghan J;Mills EG;Wall MB;Demetriou L;Wing VC;Thurston L;Owen BM;Abbara A;Rabiner EA;Dhillo WS
通讯作者：
Dhillo WS
影响因子：
3.1
作者：
Comninos AN;Anastasovska J;Sahuri-Arisoylu M;Li X;Li S;Hu M;Jayasena CN;Ghatei MA;Bloom SR;Matthews PM;O'Byrne KT;Bell JD;Dhillo WS
通讯作者：
Dhillo WS
DOI：
10.1152/ajpendo.00532.2009
发表时间：
2010-03-01
影响因子：
5.1
作者：
Catalano, Paolo N.;Di Giorgio, Noelia;Lux-Lantos, Victoria A.
通讯作者：
Lux-Lantos, Victoria A.
影响因子：
4.8
作者：
Han, Su Young;Cheong, Isaiah;Herbison, Allan E.
通讯作者：
Herbison, Allan E.