Brain-derived neurotrophic factor-mediated retrograde signaling required for the induction of long-term potentiation at inhibitory synapses of visual cortical pyramidal neurons
Brain-derived neurotrophic factor-mediated retrograde signaling required for the induction of long-term potentiation at inhibitory synapses of visual cortical pyramidal neurons
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DOI：
10.1016/j.neures.2008.02.006
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发表时间：
2008-06-01
影响因子：
2.9
通讯作者：
Komatsu, Yukio
中科院分区：
文献类型：
--
作者：
Inagaki, Tsuyoshi;Begum, Tahamina;Komatsu, Yukio
高频刺激可诱导发育中大鼠视皮层第5层锥体神经元抑制性突触的长时程增强(LTP)。这种LTP需要突触后钙离子的升高来诱导，而维持机制存在于突触前部位，提示突触前LTP的表达和逆行信号的必要性。我们研究了假设的信号是否由脑源性神经营养因子(BDNF)介导，脑源性神经营养因子在锥体神经元中表达，但不表达抑制性中间神经元。当灌流液中存在Trk受体酪氨酸激酶抑制剂K252a时，HFS不会发生LTP。当K252a在HFS后开始沐浴或将K252a加载到突触后细胞中时，HFS就会产生。在TrkB-Ig G清除BDNF或功能封闭的抗BDNF抗体存在的情况下，LTP不发生。在含有钙离子螯合剂BAPTA的细胞中，在培养液中加入BDNF使HFS能够诱导UP，而不影响基线突触传递。这些结果表明，突触后细胞释放的BDNF激活了突触前TrkB，导致LTP。由于BDNF表达的活性依赖于调节皮层抑制的成熟，因此抑制UP可能参与了这一发育过程，从而促进了视皮层经验依赖性的功能成熟。(C)2008年爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
High-frequency stimulation (HFS) induces long-term potentiation (LTP) at inhibitory synapses of layer 5 pyramidal neurons in developing rat visual cortex. This LTP requires postsynaptic Ca2+ rise for induction, while the maintenance mechanism is present at the presynaptic site, suggesting presynaptic LTP expression and the necessity of retrograde signaling. We investigated whether the supposed signal is mediated by brain-derived neurotrophic factor (BDNF), which is expressed in pyramidal neurons but not inhibitory interneurons. LTP did not occur when HFS was applied in the presence of the Trk receptor tyrosine kinase inhibitor K252a in the perfusion medium. HFS produced UP when bath application of K252a was started after HFS or when K252a was loaded into postsynaptic cells. LTP did not occur in the presence of TrkB-IgG scavenging BDNF or function-blocking anti-BDNF antibody in the medium. In cells loaded with the Ca2+ chelator BAPTA, the addition of BDNF to the medium enabled HFS to induce UP without affecting baseline synaptic transmission. These results suggest that BDNF released from postsynaptic cells activates presynaptic TrkB, leading to LTP. Because BDNF, expressed activity dependently, regulates the maturation of cortical inhibition, inhibitory UP may contribute to this developmental process, and hence experience-dependent functional maturation of visual cortex. (c) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.