BDNF locally potentiates GABAergic presynaptic machineries: Target-selective circuit inhibition
BDNF locally potentiates GABAergic presynaptic machineries: Target-selective circuit inhibition
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DOI：
10.1093/cercor/bhh130
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发表时间：
2005-03-01
期刊：
影响因子：
3.7
通讯作者：
Yamada, MK
中科院分区：
文献类型：
--
作者：
Ohba, S;Ikeda, T;Yamada, MK
抑制性神经传递对神经元回路的形成至关重要。为了检测抑制性神经传递是否在长期内接受靶向选择性调制，我们表达了脑源性神经营养因子(BDNF)的cDNA，它已被证明在体内和体外诱导少量培养的海马神经元中GABA能突触的增加。48h后，谷氨酸脱羧酶65(GAD65)的表达水平在表达BDNF的神经元周围较邻近的对照神经元选择性增强，GAD65是一种主要位于GABA能终末的GABA合成酶。外源BDNF处理48h后，GAD水平升高，GABA释放率增加。这些增强作用在表达BDNF受体(TTrkB)的显性阴性形式的神经元上的抑制性突触中减弱。这表明突触后BDNF-TrkB信号参与了抑制性突触前机制的靶向选择性增强。由于BDNF在体内以活性依赖的方式表达，这种选择性可能是维持功能神经元回路独立性的关键机制之一。
Inhibitory neurotransmission is critical for neuronal circuit formation. To examine whether inhibitory neurotransmission receives target-selective modulation in the long term, we expressed the cDNA of brain-derived neurotrophic factor (BDNF), which has been shown to induce the augmentation of GABAergic synapses in vivo and in vitro, in a small population of cultured hippocampal neurons. At 48 h after transfection, the expression level of glutamic acid decarboxylase 65 (GAD65), a GABA synthetic enzyme that resides mainly in GABAergic terminals, was selectively enhanced around the BDNF-expressing neurons, in comparison with the neighboring control neurons interposed between the BDNF-expressing neurons and inhibitory neurons. Exogenous BDNF application for 48 h also increased the GAD level and enhanced the GABA release probability. These potentiating effects were attenuated in inhibitory synapses on neurons expressing a dominant negative form of the BDNF receptor (tTrkB). This suggests that postsynaptic BDNF-TrkB signaling contributes to the target-selective potentiation of inhibitory presynaptic machineries. Since BDNF is expressed in an activity-dependent manner in vivo, this selectivity may be one of the key mechanisms by which the independence of functional neuronal circuits is maintained.