Yan Min, Xiong Mingtao, Wu Yongqiang, Lin Dong, Chen Peng, Chen Jiang, Liu Ziyang, Zhang Hang, Ren Dongyan, Fei Erkang, Lai Xinsheng, Zou Suqi, Wang Shunqi
Laboratory of Synaptic Development and Plasticity, Institute of Life Science and School of Life Sciences, Nanchang University, Nanchang, 330031, Jiangxi, China.
School of Basic Medical Science, Nanchang University, Nanchang, 330031, Jiangxi, China.
Cell Biosci. 2022 May 7;12(1):54. doi: 10.1186/s13578-022-00792-9.
Low-density lipoprotein receptor-related protein 4 (LRP4) plays a critical role in the central nervous system (CNS), including hippocampal synaptic plasticity, maintenance of excitatory synaptic transmission, fear regulation, as well as long-term potentiation (LTP).
In this study, we found that Lrp4 was highly expressed in layer II of the piriform cortex. Both body weight and brain weight decreased in Lrp4 mice without TMD (Transmembrane domain) and ICD (intracellular domain) of LRP4. However, in the piriform cortical neurons of Lrp4 mice, the spine density increased, and the frequency of both mEPSC (miniature excitatory postsynaptic current) and sEPSC (spontaneous excitatory postsynaptic current) was enhanced. Intriguingly, finding food in the buried food-seeking test was prolonged in both Lrp4 mice and Lrp4 cKO (conditional knockout of Lrp4 in the piriform cortex) mice.
This study indicated that the full length of LRP4 in the piriform cortex was necessary for maintaining synaptic plasticity and the integrity of olfactory function.
低密度脂蛋白受体相关蛋白4(LRP4)在中枢神经系统(CNS)中发挥关键作用,包括海马突触可塑性、兴奋性突触传递的维持、恐惧调节以及长时程增强(LTP)。
在本研究中,我们发现Lrp4在梨状皮质的II层中高表达。缺乏LRP4跨膜结构域(TMD)和胞内结构域(ICD)的Lrp4小鼠体重和脑重均下降。然而,在Lrp4小鼠的梨状皮质神经元中,棘密度增加,微小兴奋性突触后电流(mEPSC)和自发性兴奋性突触后电流(sEPSC)的频率均增强。有趣的是,在埋藏食物寻找试验中,Lrp4小鼠和Lrp4条件性敲除(梨状皮质中Lrp4条件性敲除)小鼠找到食物的时间均延长。
本研究表明,梨状皮质中全长LRP4对于维持突触可塑性和嗅觉功能的完整性是必要的。