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研究领域

调控神经环路发育与可塑性的分子环路机制 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。在调控神经环路发育与可塑性的机制方面,本团队近期成果包括:1. 发现早期感觉经验跨模态调节多个脑区的神经环路发育,且神经肽催产素是关键介导分子;2. 揭示了早期抚摸促进愉悦社交的神经环路机制,并阐明了PAG脑区Tac1神经元和室旁核催产素神经元在该环路中的重要作用;3. 发现系统感染早期,脑血管周细胞快速感应,并通过释放细胞因子CCL2增强多个脑区神经元的兴奋性;4 发现神经环路成熟期,感觉皮层的树突棘修剪和被保留树突棘的成熟受感觉经验协同调控,且树突棘之间对cadherin/catenin复合物这个有限资源的竞争介导了该过程。 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,以期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,有潜在的临床应用意义。

近期论文

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1. Yu H., Miao W., Ji E., Huang S., Jin S., Zhu X., Liu M.Z., Sun Y.G., Xu F., and Yu X.* (2022) Social touch-like tactile stimulation activates a tachykinin 1-oxytocin pathway to promote social interactions. Neuron 110(6):1051-1067. (highlighted by same issue Preview 110(6):909-911) 2. Yu X.* (2021) Q&A Xiang Yu. Neuron 109(19):3022-3024. 3. Cao H., Li M., Li G., Wen B., Lu Y., and Yu X.* (2020) Retinoid X receptor α regulates DHA-dependent spinogenesis and functional synapse formation in vivo. Cell Reports 31(7):107649. 4. Wang M., Yu Z., Li G., and Yu X.* (2020) Multiple morphological factors underlie experience-dependent cross-modal plasticity in the developing sensory cortices. Cerebral Cortex, 30(4):2418–2433. 5. 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) 6. 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. 7. 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. 8. 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. 9. 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; selected as “exceptional by Faculty 1000] 10. 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; selected as “exceptional” by Faculty 1000]

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