ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons
ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons
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DOI：
10.1101/lm.67804
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发表时间：
2004-03-01
影响因子：
2
通讯作者：
Pozzo-Miller, L
中科院分区：
文献类型：
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作者：
Alonso, M;Medina, JH;Pozzo-Miller, L
脑源性神经营养因子（BDNF）是中枢神经系统中突触传递和可塑性的有效调节剂，在突触前和突触后均起作用。我们最近证明，BDNF/TrkB信号增加海马CA 1区锥体神经元树突棘密度。在这里，我们测试了是否激活的主要ERK（MAPK）信号通路负责BDNF的影响脊柱生长。切片培养物转染增强型黄色荧光蛋白（eYFP）的颗粒介导的基因转移，和CA 1锥体神经元的激光扫描共聚焦显微镜成像。我们证实，BDNF（24小时）增加CA 1神经元的顶端树突棘密度。MEK（ERK激酶）抑制剂PD 98059和U 0126完全阻止了由诱导的棘密度增加。BDNF，而不影响脊柱密度本身。与其对皮质锥体神经元的作用相反，BDNF对海马锥体神经元树突复杂性的影响较小，而局部化，增加了总长度，但不影响CA 1层辐射内顶端树突的分支，而不影响层oriens中的基底树突。我们的研究结果支持这一假设，即ERK信号通路不仅介导长期突触可塑性和突触依赖性学习，但它也参与了神经营养因子触发的兴奋性突触的结构重塑。
Brain-derived neurotrophic factor (BDNF) is a potent modulator of synaptic transmission and plasticity in the CNS, acting both pre- and postsynaptically. We demonstrated recently that BDNF/TrkB signaling increases dendritic spine density in hippocampal CA1 pyramidal neurons. Here, we tested whether activation of the prominent ERK (MAPK) signaling pathway was responsible for BDNF's effects on spine growth. Slice cultures were transfected with enhanced yellow fluorescent protein (eYFP) by particle-mediated gene transfer, and CA1 pyramidal neurons were imaged by laser-scanning confocal microscopy. We confirmed that BDNF (24 h) increases spine density in apical dendrites of CA1 neurons. The MEK (ERK kinase) inhibitors PD98059 and U0126 completely prevented the increase in spine density induced by. BDNF, without having an effect on spine density by themselves. In contrast to its actions on cortical pyramidal neurons, BDNF had minor and rather localized effects on dendritic complexity in hippocampal pyramidal neurons, increasing the total length, but not the branching of apical dendrites within CA1 stratum radiatum, without affecting basal dendrites in stratum oriens. Our results support the hypothesis that the ERK-signaling pathway not only mediates long-term synaptic plasticity and hippocampal-dependent learning, but it is also involved in the structural remodeling of excitatory spine synapses triggered by neurotrophins.