Suppressed Calbindin Levels in Hippocampal Excitatory Neurons Mediate Stress-Induced Memory Loss
Suppressed Calbindin Levels in Hippocampal Excitatory Neurons Mediate Stress-Induced Memory Loss
复制标题
海马兴奋性神经元中钙结合蛋白水平的抑制介导压力引起的记忆丧失
DOI：
10.1016/j.celrep.2017.10.006
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发表时间：
2017-10-24
期刊：
影响因子：
8.8
通讯作者：
Si, Tian-Mei
中科院分区：
文献类型：
--
作者：
Li, Ji-Tao;Xie, Xiao-Meng;Si, Tian-Mei
钙结合蛋白调节细胞内钙动力学和突触可塑性。海马钙结合蛋白水平的降低与早期生活应激相关的认知障碍有关，但目前尚不清楚海马神经元不同群体中的钙结合蛋白如何导致应激诱导的记忆丧失。在这里，我们报告说，早期生活压力抑制钙结合蛋白水平在CA 1和齿状回（DG）神经元，和钙结合蛋白敲低在成年CA 1或DG兴奋性神经元模仿早期生活压力引起的记忆丧失。相比之下，CA 1中间神经元中的钙结合蛋白敲低即使在急性应激挑战后也保留了长期记忆。这些结果表明，海马兴奋性神经元而非抑制性神经元中钙结合蛋白的失调传达了对应激诱导的记忆缺陷的易感性。此外，钙结合蛋白水平下调，通过促肾上腺皮质激素释放激素受体1-nectin 3途径，这反过来又降低了肌醇单磷酸酶水平的早期生活压力。我们的研究结果强调钙结合蛋白是早期生活压力的分子靶点，也是记忆的重要底物。
Calbindin modulates intracellular Ca2+ dynamics and synaptic plasticity. Reduction of hippocampal calbindin levels has been implicated in early-life stress-related cognitive disorders, but it remains unclear how calbindin in distinct populations of hippocampal neurons contributes to stress-induced memory loss. Here we report that early-life stress suppressed calbindin levels in CA1 and dentate gyrus (DG) neurons, and calbindin knockdown in adult CA1 or DG excitatory neurons mimicked early-life stress-induced memory loss. In contrast, calbindin knockdown in CA1 interneurons preserved longterm memory even after an acute stress challenge. These results indicate that the dysregulation of calbindin in hippocampal excitatory, but not inhibitory, neurons conveys susceptibility to stress-induced memory deficits. Moreover, calbindin levels were downregulated by early-life stress through the corticotropin-releasing hormone receptor 1-nectin3 pathway, which in turn reduced inositol monophosphatase levels. Our findings highlight calbindin as a molecular target of early-life stress and an essential substrate for memory.