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Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons
Guo, Yu ; Su, Zi-jun ; Chen, Yi-kun ; Chai, Zhen
刊名JOURNAL OF NEUROCHEMISTRY
2017
关键词axon initial segment BDNF hippocampal neuron neuronal excitability neuroplasticity neurotrophins ACTIVITY-DEPENDENT RELOCATION ACTION-POTENTIAL GENERATION STRUCTURAL PLASTICITY CHANNELS BDNF TRANSPORT MAINTENANCE MODULATION MECHANISMS ANKYRIN(G)
DOI10.1111/jnc.14050
英文摘要Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development. With lowered neuronal density, the distance between the AIS and the soma increased, while neuronal excitability decreased, as shown by the increased action potential threshold and current threshold for firing an action potential. This variation in the location of the AIS was associated with cellular secretory substances, including brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3). Indeed, blocking BDNF and NT3 with TrkB-Fc eliminated the effect of conditioned medium collected from high-density cultures on AIS relocation. Elevating the extracellular concentration of BDNF or NT3 promoted movement of the AIS proximally to the soma and increased neuronal excitability. Furthermore, knockdown of neurotrophin receptors TrkB and TrkC caused distal movement of the AIS. Our results demonstrate that BDNF and NT3 regulate AIS location and neuronal excitability. These regulatory functions of neurotrophic factors provide insight into the molecular mechanisms underlying AIS biology.; National Natural Science Foundation of China [31371076]; State Key Laboratory of Membrane Biology; SCI(E); ARTICLE; 2; 260-271; 142
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/472452]  
专题生命科学学院
推荐引用方式
GB/T 7714
Guo, Yu,Su, Zi-jun,Chen, Yi-kun,et al. Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons[J]. JOURNAL OF NEUROCHEMISTRY,2017.
APA Guo, Yu,Su, Zi-jun,Chen, Yi-kun,&Chai, Zhen.(2017).Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons.JOURNAL OF NEUROCHEMISTRY.
MLA Guo, Yu,et al."Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons".JOURNAL OF NEUROCHEMISTRY (2017).
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