Brain-derived neurotrophic factor acutely depresses excitatory synaptic transmission to GABAergic neurons in visual cortical slices
Brain-derived neurotrophic factor acutely depresses excitatory synaptic transmission to GABAergic neurons in visual cortical slices
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DOI：
10.1111/j.1460-9568.2004.03523.x
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发表时间：
2004-08-01
影响因子：
3.4
通讯作者：
Tsumoto, T
中科院分区：
文献类型：
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作者：
Jiang, B;Kitamura, A;Tsumoto, T
脑源性神经营养因子（BDNF）急性调节海马和新皮层兴奋性神经元的突触传递。BDNF是否对GABA能神经元的兴奋性突触传递起类似作用的问题在以前使用皮层切片的研究中被回避了。为了解决这个问题，我们使用转基因小鼠，其中绿色荧光蛋白（GFP）的表达是由谷氨酸脱羧酶67（GAD 67）启动子调控。在从这些GAD 67-GFP敲入小鼠制备的皮质切片中，我们可以在荧光显微镜下检测GABA能神经元。BDNF的应用迅速抑制兴奋性突触后电流（EPSC）引起的第IV层刺激在大多数GFP阳性神经元在皮层的II/III层。这种作用在应用脑源性神经营养因子期间激活的突触处观察到，并被抗TrkB IgG阻断，这表明脑源性神经营养因子的急性抑制作用是活性依赖性的，并通过TrkB介导。在BDNF应用后，EPSC的振幅与配对刺激的配对脉冲比在10-100 ms的间隔下没有显著改变，这表明抑郁的部位可能是突触后。在大多数神经元中，BDNF对直接施加谷氨酸的反应也被抑制，这与BDNF的突触后作用的解释一致。BDNF的抑制作用被细胞内注射的Ca 2+螯合剂阻断，这表明Ca 2+的升高参与了EPSC的急性抑制。BDNF的这种作用见于67%的小清蛋白（PV）阳性神经元，但仅见于19%的PV阴性神经元，表明这种抑制作用偏向于PV阳性GABA能神经元。
Brain-derived neurotrophic factor (BDNF) acutely modulates synaptic transmission to excitatory neurons in hippocampus and neocortex. The question of whether BDNF acts similarly on excitatory synaptic transmission to GABAergic neurons was eluded in previous studies using cortical slices. To address this question, we used transgenic mice in which expression of green fluorescence protein (GFP) is regulated by glutamic acid decarboxylase 67 (GAD67) promoter. In cortical slices prepared from these GAD67-GFP knock-in mice, we could detect GABAergic neurons under a fluorescent microscope. An application of BDNF rapidly depressed excitatory postsynaptic currents (EPSCs) evoked by layer IV stimulation in most GFP-positive neurons in layer II/III of the cortex. This effect was seen at synapses activated during the BDNF application and blocked by anti-TrkB IgG, indicating that the acute inhibitory action of BDNF is activity-dependent and mediated through TrkB. Paired-pulse ratios of the amplitude of EPSCs to paired stimulation at intervals of 10-100 ms were not significantly changed after BDNF application, suggesting that the site of depression may be postsynaptic. Responses to directly applied glutamate were also depressed by BDNF in most of neurons, being consistent with the interpretation of postsynaptic action of BDNF. The depressive action of BDNF was blocked by an intracellular injection of a Ca2+ chelator, suggesting that a rise in Ca2+ is involved in the acute depression of EPSCs. This action of BDNF was seen in 67% of parvalbumin (PV)-positive neurons, but in only 19% of PV-negative neurons, indicating that the depressive action is biased to PV-positive GABAergic neurons.