Suv39h1 regulates memory stability by inhibiting the expression of Shank1 in hippocampal newborn neurons,European Journal of Neuroscience

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Suv39h1 regulates memory stability by inhibiting the expression of Shank1 in hippocampal newborn neurons
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2022-02-18 , DOI: 10.1111/ejn.15626
Qi‐Nan Chen _{1,

2,

3} , Xin‐Lu Ding ₁ , Xiu‐Xian Guo ₁ , Gang Zhou ₁ , Ji‐Song Guan _{1,

4}

Affiliation

Adult newborn neurons are involved in memory encoding and extinction, but the neural mechanism is unclear. We found the adult newborn neurons at 4 weeks are recruited by learning and subjected to epigenetic regulations, consequently reducing their ability to be re-recruited later. After removal of the epigenetic blockage, Suv39h1 KO mice showed an increased recruiting number of aged newborn neurons and enhanced flexibility in learning tasks. Besides NRXN1, we found SHANK1, the synaptic scaffold protein, is one of the major targets of Suv39h1, regulating memory stability. Expression of Shank1 is transiently engaged to enhance synaptogenesis during learning and is strongly suppressed by Suv39h1 from 5 h after learning. Exogenously overexpression of Shank1 in dentate gyrus increased the density of mushroom spines and decreased the persistency of old memories. Our study indicated the activity-regulated epigenetic modification in newly matured newborn neurons in hippocampus insulates temporally distinct experiences and stabilizes old memories.

中文翻译：

Suv39h1通过抑制海马新生神经元Shank1的表达调节记忆稳定性

成年新生神经元参与记忆编码和消退，但神经机制尚不清楚。我们发现 4 周时的成年新生神经元通过学习被招募并受到表观遗传调控，从而降低了它们以后被重新招募的能力。去除表观遗传障碍后，Suv39h1 KO 小鼠的老年新生神经元数量增加，学习任务的灵活性增强。除 NRXN1 外，我们还发现突触支架蛋白 SHANK1 是 Suv39h1 的主要靶标之一，可调节记忆稳定性。Shank1的表达在学习期间瞬时参与以增强突触发生，并且在学习后 5 小时被 Suv39h1 强烈抑制。Shank1的外源过表达在齿状回中增加了蘑菇刺的密度并降低了旧记忆的持久性。我们的研究表明，海马中新成熟的新生神经元中活动调节的表观遗传修饰隔离了时间上不同的体验并稳定了旧记忆。

更新日期：2022-02-18

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