Mechanisms underlying action of neurotrophic factors on postsynaptic glutamate and GABA receptors

神经营养因子对突触后谷氨酸和 GABA 受体作用的机制

基本信息

批准号：
14208094
负责人：
TSUMOTO Tadaharu
金额：
$ 34.86万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Previously we found that brain-derived neurotrophic factor (BDNF) is released from presynaptic sites in an activity-dependent manner and acts on postsynaptic neurons. In this study we attempted to see whether actions of BDNF are different between glutamatergic excitatory synapses and GABAergic inhibitory synapses, and further to elucidate mechanisms underlying such actions. We obtained the following results.1.Using mixed neuron culture preparations obtained from green fluorescence protein (GFP) mice and BDNF knockout mice, we explored what actions presynaptic BDNF exerts on postsynaptic neurons. We found that presynaptic BDNF promotes dendritic development of postsynaptic GABAergic neurons.2.Actions of exogenous BDNF on GABAergic synapses were investigated in solitary GABAergic neurons cultured on glial microisland to completely exclude possible involvement of excitatory synapses from the observed effects of BDNF. We found that BDNF increased the number of active GABAergic synapses.3.Roles of endogenous BDNF in development of glutamatergic synapses were investigated in barrel cortex of BDNF knockout and wild type mice. We found that silent synapses, which consist only of NMDA receptors, are abnormally increased in BDNF knockout mice, and this is rescued by exogenously applied BDNF.4.Actions of exogenous BDNF on excitatory synapses on GABAergic neurons were not studied previously. We addressed this issue by using GAD67-GFP knock-in mice, in which GABAergic neurons are easily identified. We found that BDNF acutely depressed function of excitatory synapses to GABAergic neurons.

以前，我们发现脑衍生的神经营养因子（BDNF）以活性依赖性方式从突触前部位释放，并作用于突触后神经元。在这项研究中，我们试图查看BDNF的作用在谷氨酸能兴奋性突触和GABA能抑制突触之间是否有所不同，并进一步阐明了这种行动的基础机制。我们获得了以下结果。1。使用从绿色荧光蛋白（GFP）小鼠和BDNF敲除小鼠获得的混合神经元培养物制剂，我们探索了突触前BDNF对突触后神经元的作用。我们发现，突触前BDNF促进了突触后GABA能神经元的树突状发展。2。外源性BDNF对Gabaergic Synapses的作用是在单独的GABA能神经元上培养的Gabaergic神经元的，这些神经元在神经胶质微岛的单独Gabagaergic神经元中进行了研究，以完全排除兴奋性的兴奋性突触的参与，从而将兴奋性效应从观察到的Bdn sos bdn so n of bdn femption。我们发现BDNF增加了活跃的GABA能突触的数量。3。内源性BDNF在BDNF敲除和野生型小鼠的桶皮层中研究了内源性BDNF在谷氨酸盐突触中的发展。我们发现，仅由NMDA受体组成的无声突触在BDNF敲除小鼠中异常增加，这是通过外源施用的BDNF.4。我们使用GAD67-GFP敲入小鼠解决了这个问题，其中很容易鉴定出GABA能神经元。我们发现，兴奋性突触对GABA能神经元的BDNF急剧抑郁症的功能。