A novel form of synaptic plasticity in field CA3 of hippocampus requires GPER1 activation and BDNF release.
A novel form of synaptic plasticity in field CA3 of hippocampus requires GPER1 activation and BDNF release.
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DOI：
10.1083/jcb.201504092
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发表时间：
2015-09-28
期刊：
影响因子：
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通讯作者：
Baudry M
中科院分区：
文献类型：
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作者：
Briz V;Liu Y;Zhu G;Bi X;Baudry M
雌激素通过GPER1介导的BDNF释放、mTOR依赖的蛋白质合成和蛋白酶体活性等机制，在苔藓纤维CA3突触上阻断代谢性谷氨酸受体依赖性的长期抑制。雌激素通过对膜相关受体的快速作用，是海马区突触可塑性和记忆巩固的重要调节剂。在这里，我们发现雌二醇和G蛋白偶联雌激素受体1(GPER1)特异性激动剂G1都能快速诱导脑源性神经营养因子(BDNF)的释放，导致活性调节细胞骨架相关(Arc)蛋白翻译的瞬时刺激和含有GluA1的AMPA受体在海马CA3区的内化。我们还表明，I型代谢性谷氨酸受体(MGluR)的激活不会诱导苔藓纤维途径的Arc翻译或长期抑制(LTD)，而不是它在CA1中的作用，它只在GPER1刺激后触发LTD。此外，这种形式的mGluR依赖的LTD与泛素化和蛋白酶体介导的GluA1降解有关，并被蛋白酶体抑制所阻止。总体而言，我们的研究确定了雌激素和脑源性神经营养因子调节成年大脑中海马区突触可塑性的新机制。
Estrogen gates metabotropic glutamate receptor–dependent long-term depression at mossy fiber–CA3 synapses through a mechanism involving GPER1-mediated BDNF release, mTOR-dependent protein synthesis, and proteasome activity. Estrogen is an important modulator of hippocampal synaptic plasticity and memory consolidation through its rapid action on membrane-associated receptors. Here, we found that both estradiol and the G-protein–coupled estrogen receptor 1 (GPER1) specific agonist G1 rapidly induce brain-derived neurotrophic factor (BDNF) release, leading to transient stimulation of activity-regulated cytoskeleton-associated (Arc) protein translation and GluA1-containing AMPA receptor internalization in field CA3 of hippocampus. We also show that type-I metabotropic glutamate receptor (mGluR) activation does not induce Arc translation nor long-term depression (LTD) at the mossy fiber pathway, as opposed to its effects in CA1, and it only triggers LTD after GPER1 stimulation. Furthermore, this form of mGluR-dependent LTD is associated with ubiquitination and proteasome-mediated degradation of GluA1, and is prevented by proteasome inhibition. Overall, our study identifies a novel mechanism by which estrogen and BDNF regulate hippocampal synaptic plasticity in the adult brain.