Regulation of hippocampal long term depression by Neuroligin 1
Regulation of hippocampal long term depression by Neuroligin 1
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Neuroligin 1 对海马长期抑郁的调节。
DOI：
10.1016/j.neuropharm.2018.09.035
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发表时间：
2018-12-01
影响因子：
4.7
通讯作者：
Jia, Zhengping
中科院分区：
文献类型：
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作者：
Dang, Rui;Qi, Junxia;Jia, Zhengping
神经胶质素（NLGs）是突触后粘附分子，在突触发育和成熟过程中发挥重要作用，但其对成熟突触可塑性的影响尚不清楚。在这项研究中，我们调查的参与NLG 1在海马长期抑郁症（LTD），持久的突触可塑性的关键形式，记忆形成和大脑疾病的关键，通过使用小鼠缺乏NLG 1的表达。我们发现，尽管NLG 1纯合子（NLG 1-/-）小鼠在NMDA受体-（NMDAR-LTD）或代谢型谷氨酸受体依赖性LTD（mGluR-LTD），杂合子（NLG 1 +/-）小鼠的两种形式的LTD均显著改变，其特征在于不存在NMDAR-LTD但增强mGluR-LTD。但NLG 1-/-小鼠的突触蛋白质（包括PSD 95、GluA 2和丝氨酸845处的磷酸化GluA 1）没有改变，所有这些都参与LTD的表达。NLG 1 +/-小鼠还表现出自闭症样行为，包括梳理增加和识别记忆受损。我们进一步表明，NLG 1的近亲NLG 3的表达在NLG 1-/-小鼠中升高，但在NLG 1 +/-小鼠中没有，这表明NLG 1-/-小鼠中缺乏LTD缺陷可能是由于NLG 3增加。我们的研究结果揭示了NLG 1在LTD调节中的基因剂量依赖性作用，并表明NLG 1蛋白水平的适度变化可能足以导致大脑疾病中的突触和行为缺陷，其中基因突变的拷贝数变异和半合子是常见的。
Neuroligins (NLGs) are postsynaptic adhesion molecules known to play essential roles in synapse development and maturation, but their effects on synaptic plasticity at mature synapses remain unclear. In this study, we investigate the involvement of NLG1 in hippocampal long-term depression (LTD), a key form of long lasting synaptic plasticity, critical for memory formation and brain disorders, by using mice deficient in the expression of NLG1. We find that although NLG1 homozygous (NLG1-/-) mice show no impairments in either NMDA receptor- (NMDAR-LTD) or metabotropic glutamate receptor-dependent LTD (mGluR-LTD), the heterozygous (NLG1 +/-) mice are significantly altered in both forms of LTD characterized by the absence of NMDAR-LTD but enhanced mGluR-LTD. Accordingly, the NLG1 +/-, but not the NLG1 -/- mice are altered in synaptic proteins, including PSD95, GluA2 and phosphorylated GluA1 at serine 845, all of which are involved in the expression of LTD. The NLG1 +/- mice also exhibit autistic-like behaviors including increased grooming and impaired recognition memory. We further show that the expression of NLG3, a close family member of NLG1, is elevated in the NLG1 -/-, but not in NLG1 +/- mice, suggesting that the lack of LTD deficits in the NLG1 -/- mice might be due to the increased NLG3. Our results reveal a gene dosage dependent role for NLG1 in the regulation of LTD and suggest that moderate changes in NLG1 protein level may be sufficient to cause synaptic and behavior deficits in brain disorders where copy number variants and hemizygosity of gene mutations are common.