Zhu Ling-Shuang, Lai Chuan, Zhou Chao-Wen, Chen Hui-Yang, Liu Zhi-Qiang, Guo Ziyuan, Man Hengye, Du Hui-Yun, Lu Youming, Hu Feng, Chen Zhiye, Shu Kai, Zhu Ling-Qiang, Liu Dan
Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Cell Discov. 2024 Aug 20;10(1):87. doi: 10.1038/s41421-024-00706-8.
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.
个体在与同种个体的竞争性互动中持续取得成功会强烈影响其社会等级制度。内侧前额叶皮质（mPFC）是介导社会竞争和等级制度的关键脑区。然而，mPFC中神经集合的分子调控机制仍不清楚。在这里，我们证明，在前边缘皮质（PL）的兴奋性神经元中，lncRNA Sera重塑了Pkm外显子9和外显子10的利用，导致高度竞争性小鼠中Pkm1/2比率降低。通过采用四环素诱导/关闭系统，我们通过控制PL兴奋性神经元中Pkm2的表达来破坏或重建正常的Pkm1/2比率。我们发现，长期的Pkm2调节通过磷酸化GluA1的Ser845位点，诱导及时的竞争改变和滞后的等级变化。总之，本研究揭示了lncRNA Sera/Pkm2通路在通过重塑mPFC中的神经集合实现社会竞争向等级转变中的关键作用。
