Estradiol acutely suppresses inhibition in the hippocampus through a sex-specific endocannabinoid and mGluR-dependent mechanism.

Estradiol acutely suppresses inhibition in the hippocampus through a sex-specific endocannabinoid and mGluR-dependent mechanism.
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DOI:
10.1016/j.neuron.2012.03.035
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发表时间:
2012-06-07
期刊:
影响因子:
16.2
通讯作者:
Woolley CS
Woolley CS
中科院分区:
医学1区
文献类型:
--
作者:
Huang GZ;Woolley CS

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类固醇,17β-雌二醇(E2),是众所周知的影响海马功能,如记忆,情感行为和癫痫。越来越多的人认识到,除了对卵巢E2有反应外,男性和女性的海马体也会合成E2作为一种神经类固醇,可以急性调节突触功能。以前关于海马中E2的急性作用的研究主要集中在兴奋性突触上。在这里,我们发现E2快速抑制海马CA1的抑制性突触传递。E2通过雌激素受体的α形式刺激突触后mglur1依赖的内源性大麻素,anandamide的动员,然后逆行抑制GABA从含有CB1受体的抑制性突触前按钮释放。值得注意的是,E2的这种作用是性别特异性的,发生在女性身上,而不是男性。E2对内源性大麻素张力的急性调节和随之而来的抑制作用的抑制提供了一种新的机制,即神经类固醇E2可以以性别特异性的方式调节海马依赖行为。
The steroid, 17β-estradiol (E2), is well known to influence hippocampal functions such as memory, affective behaviors, and epilepsy. There is growing awareness that in addition to responding to ovarian E2, the hippocampus of both males and females synthesizes E2 as a neurosteroid that could acutely modulate synaptic function. Previous work on acute E2 actions in hippocampus has focused on excitatory synapses. Here, we show that E2 rapidly suppresses inhibitory synaptic transmission in hippocampal CA1. E2 acts through the α form of the estrogen receptor to stimulate postsynaptic mGluR1-dependent mobilization of the endocannabinoid, anandamide, which then retrogradely suppresses GABA release from CB1 receptor-containing inhibitory presynaptic boutons. Remarkably, this effect of E2 is sex-specific, occurring in females but not males. Acute E2 modulation of endocannabinoid tone and consequent suppression of inhibition provides a new mechanism by which neurosteroid E2 could modulate hippocampus-dependent behaviors in a sex-specific manner.
DOI: 10.1016/s0304-3940(01)02083-3
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