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Molecular mechanisms of error siganl-induced synaptic plasticity related to bird song learning

错误信号诱导的鸟鸣学习突触可塑性的分子机制

基本信息

批准号：
13680878
负责人：
SAKAGUCHI Hironobu
金额：
$ 2.18万
依托单位：
DOKKYO UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680878/
关键词：
Bengalese finch Zebra finch Song learning Protein kinase C Auditory feedback Song control nuclei Synaptic plasticity Error signal プロテインキナーゼC 脳可塑性

项目摘要

1. An output signal (error signal) from the anterior forebrain pathway in songbird is essential for juvenile song learning and adult song maintenance. In adult Bengalese finches, song patterns remarkably alter after deafening, remain unstable, then stabilize, similarly to the song acquisition in young. In parallel with the song alteration, expression of PKC, considered a molecular marker of synaptic plasticity, increased transiently after deafening, and then decreased gradually in the RA. We lesioned unilaterally the IMAN, which projects to the RA. Following a week, we then deprived them of auditory input by cochlear removal. The immunoreactivity of PKC β1, a subtype of PKC, increased in the RA of intact hemisphere at 2 weeks after deafening. However, in the RA of the lesioned side, PKC immunoreactivity was less intense than that of the non-lesioned side. Namely, the deafened-induced PKC expression was suppressed by the lesion of IMAN. These results suggest that the error signal induces the increase of PKC activity in the RA related to the plasticity of song alterations.2. In order to clarify the molecular mechanism of error signal-induced PKC activation, two experiments were carried out. First, Ca^<2+> concentration was measured in the brain slice preparation of zebra finch using the fluorescent Ca^<2+> indicator FURA-2-AM. Glutamate caused an increase of intracellular Ca^<2+> concentration in RA neurons. This increase was inhibited by the NMDA receptor antagonist, AP5. Second, we examined the PKC expression in the RA slice preparation after glutamate stimulation for 10 min using PKCβ1 immunohistochemistry. Consequently, glutamate induced the activation of PKC by the translocation from cytosol to membrane. These results indicate that the translocation of the PKC by intracellular Ca^<2+> elevation through NMDA receptor is concerned in the initial stage of error signal-induced-plasticity in RA.

1.鸣禽前前脑通路的一个输出信号（错误信号）对于幼年鸣禽的鸣唱学习和成年鸣禽的鸣唱维持是必不可少的。在成年孟加拉雀，歌曲模式显着改变后，震耳欲聋，保持不稳定，然后稳定，类似的歌曲获得在年轻的。与鸣唱改变平行的是，被认为是突触可塑性的分子标志物的PKC表达在聋后短暂增加，然后在RA中逐渐减少。我们单方面损伤IMAN，它投射到RA。一周后，我们通过耳蜗移除剥夺了他们的听觉输入。在聋后2周，完整侧RA中PKC β1的免疫反应性增强。而在病变侧RA，PKC免疫反应性较非病变侧弱。也就是说，IMAN的损伤抑制了地塞米松诱导的PKC表达。这些结果提示错误信号诱导RA中PKC活性的增加与鸣唱改变的可塑性有关.为了阐明错误信号诱导PKC激活的分子机制，进行了两个实验。首先，用荧光Ca^2+指示剂FURA-2-AM测定了斑胸草雀脑切片中的Ca^2+浓度。谷氨酸引起RA神经元内Ca^<2+>浓度增加。这种增加被NMDA受体拮抗剂AP 5抑制。其次，我们用PKCβ1免疫组织化学方法检测了谷氨酸刺激10分钟后RA切片制备物中PKC的表达。因此，谷氨酸通过从胞浆到膜的移位来诱导PKC的激活。这些结果表明，通过NMDA受体引起的细胞内Ca^2+升高引起的PKC转位参与了RA错误信号诱导的可塑性的初始阶段。