Pre-synaptic TrkB in basolateral amygdala neurons mediates BDNF signaling transmission in memory extinction.
Pre-synaptic TrkB in basolateral amygdala neurons mediates BDNF signaling transmission in memory extinction.
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基底外侧杏仁核神经元中的突触前 TrkB 介导记忆消退中的 BDNF 信号传导。
DOI：
10.1038/cddis.2017.302
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发表时间：
2017-07-27
影响因子：
9
通讯作者：
Sun T
中科院分区：
文献类型：
--
作者：
Li Y;Wang D;Li Y;Chu H;Zhang L;Hou M;Jiang X;Chen Z;Su B;Sun T
脑源性神经营养因子（BDNF）及其高亲和力受体TrkB在记忆消退中起重要作用。我们的前期工作表明，JNK相互作用蛋白3（JNK interacted protein 3，JIP 3）通过其卷曲螺旋结构域1（coiled-coil domain 1，CC 1）与TrkB的直接结合介导TrkB的顺行轴突运输。本研究构建了荧光CC 1和增强型绿色荧光蛋白（EGFP）融合蛋白CC 1-EGFP，发现CC 1-EGFP能特异性阻断TrkB的轴突顺行转运及其在突触前位点的定位。与此一致，TrkB介导的突触前囊泡释放和逆行轴突信号传递被CC 1-EGFP破坏。基底外侧杏仁核（BLA）中CC 1-EGFP的神经元表达损害恐惧记忆消退。并且，它阻断了BDNF在BLA诱导的下边缘前额叶皮层（IL）中TrkB磷酸化的增强。总之，这项研究不仅表明，突触前TrkB在BLA神经元是必要的记忆消退，并有助于BDNF信号转导从BLA到IL，但也提供了CC 1-EGFP作为一种新的工具，在体外和体内特异性调节突触前TrkB的表达。
Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, TrkB, play an essential role in memory extinction. Our previous work has shown that JIP3 (JNK interacted protein 3) mediates anterograde axonal transport of TrkB through the direct binding of its coiled-coil domain 1 (CC1) with TrkB. Here, we constructed a fluorescent CC1 and enhanced green fluorescent protein (EGFP) fused protein, CC1-EGFP, and found that CC1-EGFP could specifically interrupt TrkB anterograde axonal transport and its localization at the pre-synaptic site. Consistent with this, TrkB-mediated pre-synaptic vesicle release and retrograde axonal signaling transmission were disrupted by CC1-EGFP. Neuronal expression of CC1-EGFP in the basolateral amygdala (BLA) impaired fear memory extinction. And, it blocked BDNF in the BLA-induced enhancement of TrkB phosphorylation in the infralimbic prefrontal cortex (IL). Together, this study not only suggests that pre-synaptic TrkB in BLA neurons is necessary for memory extinction and contributes to the BDNF signaling transduction from the BLA to IL, but also provides CC1-EGFP as a novel tool to specifically regulate pre-synaptic TrkB expression in vitro and in vivo.
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