17β estradiol recruits GluN2B-containing NMDARs and ERK during induction of long-term potentiation at temporoammonic-CA1 synapses.
17β estradiol recruits GluN2B-containing NMDARs and ERK during induction of long-term potentiation at temporoammonic-CA1 synapses.
复制标题
17β 雌二醇在颞氨-CA1 突触诱导长期增强过程中招募含 GluN2B 的 NMDAR 和 ERK。
DOI：
10.1002/hipo.22495
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发表时间：
2016
期刊：
影响因子：
3.5
通讯作者：
McMahon,LoriL
中科院分区：
文献类型：
--
作者：
Smith,CarolineC;Smith,LindseyA;Bredemann,TerukoM;McMahon,LoriL
当循环17β雌二醇（E2）升高至动情前期水平时，由于海马突触的突触功能增强，雌性啮齿动物、非人灵长类动物和女性的海马依赖性学习和记忆增强。我们先前报道，仅当树突棘密度、NMDAR/AMPAR比值和含GluN 2B的NMDA受体（NMDARs）介导的电流同时增加时，向年轻成年卵巢切除（OVX）雌性大鼠给予发情前期水平的E2才能增加CA 3-Schaffer侧支（SC）-CA 1突触的LTP幅度。我们还报道，CA 1区GluN 2B介导的NMDAR电流的增加与E2诱导的新物体识别增加有因果关系，将突触功能的增强与学习和记忆的改善联系在一起。除了SC输入外，从颞氨（TA）通路中的内嗅皮层到腔隙-分子层中的CA 1远端树突的神经支配对于空间记忆的形成和提取至关重要。目前尚不清楚E2是否与SC-CA 1突触类似地调节TA-CA 1突触。在这里，我们报告了E2注射后24小时，CA 1锥体细胞远端树突上的树突棘密度和TA-CA 1突触处含GluN 2B的NMDAR介导的电流增加，与我们之前在SC-CA 1突触中的发现相似。然而，与SC-CA 1突触相反，TA-CA 1突触的AMPAR传递显着增加，并且对LTP幅度没有影响。药理学阻断含GluN 2B的NMDAR或ERK激活（发生在突触下游而非突触外含GluN 2B的NMDAR）仅在E2处理大鼠的切片中减弱LTP幅度。这些数据表明，E2在诱导LTP中对含GluN 2B的NMDAR和ERK信号传导起因果作用，这是溶剂处理的OVX雌性大鼠中TA-CA 1突触处LTP诱导不需要的细胞机制。© 2015威利期刊公司.
When circulating 17β estradiol (E2) is elevated to proestrous levels, hippocampus‐dependent learning and memory is enhanced in female rodents, nonhuman primates, and women due to heightened synaptic function at hippocampal synapses. We previously reported that proestrous‐like levels of E2 administered to young adult ovariectomized (OVX) female rats increases the magnitude of LTP at CA3 Schaffer collateral (SC)‐CA1 synapses only when dendritic spine density, the NMDAR/AMPAR ratio, and current mediated by GluN2B‐containing NMDA receptors (NMDARs) are simultaneously increased. We also reported that this increase in GluN2B‐mediated NMDAR current in area CA1 is causally related to the E2‐induced increase in novel object recognition, tying together heightened synaptic function with improved learning and memory. In addition to SC inputs, innervation from the entorhinal cortex in the temporoammonic (TA) pathway onto CA1 distal dendrites in stratum lacunosum‐moleculare is critical for spatial memory formation and retrieval. It is not known whether E2 modulates TA‐CA1 synapses similarly to SC‐CA1 synapses. Here, we report that 24 hours post‐E2 injection, dendritic spine density on CA1 pyramidal cell distal dendrites and current mediated by GluN2B‐containing NMDARs at TA‐CA1 synapses is increased, similarly to our previous findings at SC‐CA1 synapses. However, in contrast to SC‐CA1 synapses, AMPAR transmission at TA‐CA1 synapses is significantly increased, and there is no effect on the LTP magnitude. Pharmacological blockade of GluN2B‐containing NMDARs or ERK activation, which occurs downstream of synaptic but not extrasynaptic GluN2B‐containing NMDARs, attenuates the LTP magnitude only in slices from E2‐treated rats. These data show that E2 recruits a causal role for GluN2B‐containing NMDARs and ERK signaling in the induction of LTP, cellular mechanisms not required for LTP induction at TA‐CA1 synapses in vehicle‐treated OVX female rats. © 2015 Wiley Periodicals, Inc.