Hypothalamic PVN CRH Neurons Signal Through PVN GABA Neurons to Suppress GnRH Pulse Generator Frequency in Female Mice.
Hypothalamic PVN CRH Neurons Signal Through PVN GABA Neurons to Suppress GnRH Pulse Generator Frequency in Female Mice.
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DOI：
10.1210/endocr/bqad075
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发表时间：
2023-04-17
期刊：
影响因子：
4.8
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中科院分区：
文献类型：
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下丘脑室旁核（PVN）中的促肾上腺皮质激素释放激素（CRH）神经元是应激反应的中枢。PVN CRH神经元的化学发生激活降低LH脉冲频率，但机制尚不清楚。在本研究中，PVN CRH神经元的光遗传学刺激抑制雌二醇替代卵巢切除CRH-cre小鼠的LH脉冲频率，这种作用分别通过PVN内GABAA或GABAB受体拮抗作用增强或减弱。PVN CRH神经元向局部GABA神经元发出信号，这可能提供了PVN CRH神经元抑制LH脉冲频率的可能间接机制。雌激素替代Vgat-cre-td Tomato小鼠下丘脑弓状核内潜在PVN GABA能投射终末的光遗传学刺激经弓状核植入的光纤抑制LH脉冲频率。为了进一步确定PVN CRH神经元是否通过PVN GABA神经元发出信号以抑制LH脉动，我们将重组酶小鼠与交叉载体组合以选择性地靶向这些神经元。使用CRH-cre：：Vgat-FlpO小鼠，所述CRH-cre：：Vgat-FlpO小鼠在非GABA能CRH神经元中单独表达刺激性视蛋白ChRmine或与PVN中非CRH表达GABA神经元中的抑制性视蛋白NpHR 3.3组合。非GABA能CRH神经元的光遗传刺激抑制脉冲LH分泌;然而，LH脉冲频率不受影响时，CRH神经元被刺激，PVN GABA神经元同时被抑制。总之，这些研究表明，响应PVN CRH神经元激活的LH脉冲频率的抑制是由PVN固有的GABA能信号传导介导的，并且可能将PVN GABA能投射纳入下丘脑GnRH脉冲发生器。
Corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) are central to the stress response. Chemogenetic activation of PVN CRH neurons decreases LH pulse frequency but the mechanism is unknown. In the present study, optogenetic stimulation of PVN CRH neurons suppressed LH pulse frequency in estradiol-replaced ovariectomized CRH-cre mice, and this effect was augmented or attenuated by intra-PVN GABAA or GABAB receptor antagonism, respectively. PVN CRH neurons signal to local GABA neurons, which may provide a possible indirect mechanism by which PVN CRH neurons suppress LH pulse frequency. Optogenetic stimulation of potential PVN GABAergic projection terminals in the hypothalamic arcuate nucleus in ovariectomized estradiol-replaced Vgat-cre-tdTomato mice via an optic fiber implanted in the arcuate nucleus suppressed LH pulse frequency. To further determine whether PVN CRH neurons signal through PVN GABA neurons to suppress LH pulsatility, we combined recombinase mice with intersectional vectors to selectively target these neurons. CRH-cre::Vgat-FlpO mice expressing the stimulatory opsin ChRmine in non-GABAergic CRH neurons alone or in combination with the inhibitory opsin NpHR3.3 in non-CRH-expressing GABA neurons in the PVN were used. Optogenetic stimulation of non-GABAergic CRH neurons suppressed pulsatile LH secretion; however, LH pulse frequency was not affected when CRH neurons were stimulated and PVN GABA neurons were simultaneously inhibited. Together, these studies demonstrate that suppression of LH pulse frequency in response to PVN CRH neuronal activation is mediated by GABAergic signalling intrinsic to the PVN and may incorporate PVN GABAergic projection to the hypothalamic GnRH pulse generator.
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影响因子：
64.5
作者：
Kishi KE;Kim YS;Fukuda M;Inoue M;Kusakizako T;Wang PY;Ramakrishnan C;Byrne EFX;Thadhani E;Paggi JM;Matsui TE;Yamashita K;Nagata T;Konno M;Quirin S;Lo M;Benster T;Uemura T;Liu K;Shibata M;Nomura N;Iwata S;Nureki O;Dror RO;Inoue K;Deisseroth K;Kato HE
通讯作者：
Kato HE
DOI：
10.1016/s0960-0760(01)00094-2
发表时间：
2001-09-01
影响因子：
4.1
作者：
Genazzani, AD;Bersi, C;Genazzani, AR
通讯作者：
Genazzani, AR
影响因子：
25
作者：
Hewitt, Sarah A.;Wamsteeker, Jaclyn I.;Bains, Jaideep S.
通讯作者：
Bains, Jaideep S.
DOI：
10.1073/pnas.1713897114
发表时间：
2017-11-21
影响因子：
11.1
作者：
Clarkson, Jenny;Han, Su Young;Herbison, Allan E.
通讯作者：
Herbison, Allan E.
影响因子：
4.3
作者：
Dabrowska J;Hazra R;Guo JD;Dewitt S;Rainnie DG
通讯作者：
Rainnie DG