Postsynaptic lncRNA Sera/Pkm2 pathway orchestrates the transition from social competition to rank by remodeling the neural ensemble in mPFC

突触后 lncRNA Sera/Pkm2 通路通过重塑 mPFC 中的神经集合来协调从社会竞争到等级的转变

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作者:Ling-Shuang Zhu #, Chuan Lai #, Chao-Wen Zhou #, Hui-Yang Chen, Zhi-Qiang Liu, Ziyuan Guo, Hengye Man, Hui-Yun Du, Youming Lu, Feng Hu, Zhiye Chen, Kai Shu, Ling-Qiang Zhu, Dan Liu

Abstract

Individuals' continuous success in competitive interactions with conspecifics strongly affects their social hierarchy. Medial prefrontal cortex (mPFC) is the key brain region mediating both social competition and hierarchy. However, the molecular regulatory mechanisms underlying the neural ensemble in the mPFC remains unclear. Here, we demonstrate that in excitatory neurons of prelimbic cortex (PL), lncRNA Sera remodels the utilization of Pkm Exon9 and Exon10, resulting in a decrease in the Pkm1/2 ratio in highly competitive mice. By employing a tet-on/off system, we disrupt or rebuild the normal Pkm1/2 ratio by controlling the expression of Pkm2 in PL excitatory neurons. We find that long-term Pkm2 modulation induces timely competition alteration and hysteretic rank change, through phosphorylating the Ser845 site of GluA1. Together, this study uncovers a crucial role of lncRNA Sera/Pkm2 pathway in the transition of social competition to rank by remodeling neural ensemble in mPFC.

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