于翔 Emailyuxiang01(at)pku(dot)edu(dot)cn
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详细描述
研究方向
大脑的正常认知功能依赖于其复杂而精细的神经网络。来自环境的刺激对大脑中神经元的生长、突触的形成，以及神经环路的建立至关重要。本团队前期的工作发现发育早期的大脑具有与成年大脑显著不同的可塑性机制，具体发现包括：1）早期感觉经验通过跨模态全局机制调节小鼠多个脑区的神经环路发育，且神经肽催产素是介导该过程的关键分子；2）系统性炎症早期，脑血管周细胞快速感应感染信号，并通过释放细胞因子CCL2增强多个脑区神经元的兴奋性；3）神经环路成熟期，小鼠感觉皮层的树突棘修剪和被保留树突棘的成熟被感觉经验协同调控，且树突棘之间对“cadherin/catenin复合物”这种有限资源的竞争介导了这一过程。
基于上述结果，我们提出了“早期神经环路跨模态全局发育假说”。 发育早期的大脑具有更高的可塑性——且部分脑功能具有关键期——是神经科学公认的现象，然而介导这些过程的机制仍不很清楚。本团队将结合单细胞表达谱分析、分子生物学、遗传学、免疫组化等方法，解析介导该过程的分子机制；还将运用电生理、光学成像、行为学等方法研究感觉经验与环境因素对发育早期神经元、胶质细胞和神经血管单元的调控，从而解析介导该可塑性的细胞与环路机制。解析幼年大脑发育早期跨模态可塑性的机制对理解大脑的工作原理有重要理论意义。孤独症谱系障碍、智力障碍等发育性神经系统疾病严重影响儿童健康。通过解析幼年大脑的工作原理，在发育早期给予有遗传风险的个体促进其大脑发育的个体化药物治疗与行为干预，有重要临床与社会意义。


代表性科研论文
1. Duan, L., Zhang, X.D., Miao, W.Y., Sun, Y.J., Xiong, G., Wu, Q., Li, G., Yang, P., Yu, H., Li, H., Wang, Y., Zhang, M., Hu, L.Y., Tong, X., Zhou, W.H., Yu, X.* (2018) PDGFRβ cells rapidly relay inflammatory signal from the circulatory system to neurons via chemokine CCL2. Neuron 100(1):183-200. (highlighted by same issue Preview 100(1):11-13
2. Hu C.C., Xu X.*, Xiong G.L., Xu Q., Zhou B.R., Li C.Y., Qin Q., Liu C.X., Li H.P., Sun Y.J.*, Yu X.* (2018) Alterations in plasma cytokine levels in Chinese children with autism spectrum disorder. Autism Research 11(7):989-999
3. Li M.Y., Miao W.Y., Wu Q.Z., He S.J., Yan G., Yang Y., Liu J.J., Taketo M.M. and Yu, X.* (2017) A critical role of presynaptic Cadherin/Catenin/p140cap complexes in stabilizing spines and functional synapses in the neocortex. Neuron 94(6):1155-1172
4. Zhang S.X., Duan L.H., He S.J., Zhuang G.F. and Yu X.* (2017) Phosphatidylinositol 3,4-bisphosphate regulates neurite initiation and dendrite morphogenesis via actin aggregation. Cell Res. 27(2):253-273.
5. Wang M., Li H., Takumi T., Qiu Z., Xu X.*, Yu X.* and Bian W.J.* (2017) Distinct Defects in Spine Formation or Pruning in Two Gene Duplication Mouse Models of Autism Neurosci. Bull. 33(2):143-152
6. Bian W.J., Miao W.Y., He S.J., Qiu Z. and Yu, X.* (2015) Coordinated spine pruning and maturation mediated by inter-spine competition for cadherin/catenin complexes. Cell 162(4): 808-822 (highlighted by Nat. Rev. Neurosci. 16(10):577
7. Zheng J.J., Li S.J., Zhang X.D., Miao W.Y., Zhang D., Yao H. and Yu, X.* (2014) Oxytocin mediates early experience–dependent cross-modal plasticity in the sensory cortices. Nat. Neurosci. 17(3):391-399 [highlighted by same issue News and Views 17(3), 340 and by Nat. Rev. Neurosci. 15(3):139
8. Peng Y.R., Zeng S.Y., Song H.L., Li M.Y., Yamada M.K., and Yu X.* (2010) Postsynaptic spiking homeostatically induces cell-autonomous regulation of inhibitory inputs via retrograde signaling J. Neurosci. 30(48):16220-16231, cover story.
9. He S., Ma J., Liu N. and Yu, X.* (2010) Early enriched environment promotes neonatal GABAergic neurotransmission and accelerates synapse maturation. J. Neurosci. 30(23):7910-7916.
10.Tan Z.J., Peng Y., Song H.L. and Yu X.* (2010) N-cadherin dependent neuron-neuron interaction is required for the maintenance of activity-induced dendrite growth. Proc. Natl. Acad. Sci. USA 107(21):9873-9878, cover story.