Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats.

Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats.
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DOI:
10.3389/fncel.2014.00033
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发表时间:
2014
影响因子:
5.3
通讯作者:
Fukuda A
Fukuda A
中科院分区:
医学2区
文献类型:
--
作者:
Qian T;Chen R;Nakamura M;Furukawa T;Kumada T;Akita T;Kilb W;Luhmann HJ;Nakahara D;Fukuda A

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在发育中的大脑皮层中,边缘区 (MZ) 由早期生成的神经元(例如 Cajal-Retzius 细胞)组成,在细胞迁移和层压中发挥着重要作用。越来越多的证据表明,MZ 中广泛存在由 γ-氨基丁酸 (GABA) 介导的兴奋性神经传递。 Cajal-Retzius细胞不仅表达GABAA受体,还表达甘氨酸受体的α2/β亚基,并且由于高[Cl−]i而表现出甘氨酸受体介导的去极化。然而,甘氨酸受体及其内源性激动剂在 MZ 神经传递过程中的生理作用尚未阐明。为了解决这个问题,我们使用电压敏感染料 JPW1114 对新生大鼠的切向新皮质切片进行 MZ 光学成像。单一的电刺激会引起动作电位相关的光信号,该信号在 MZ 上呈放射状传播。信号幅度不受谷氨酸受体阻滞剂的影响,但受到 GABAA 或甘氨酸受体拮抗剂的抑制。两种拮抗剂的联合应用几乎消除了信号。 20 µM 布美他尼对 Na+、K+-2Cl− 协同转运蛋白的抑制作用降低了信号,表明该转运蛋白有助于激发。通过高效液相色谱法对切向新皮质切片进行微透析获得的间质液进行分析,结果表明,响应电刺激,MZ 中释放了 GABA 和牛磺酸,但没有释放甘氨酸或谷氨酸。通过添加电压敏感的 Na+ 通道阻滞剂,可以减少牛磺酸在环境中的释放。免疫组织化学和免疫电镜表明,牛磺酸储存在 MZ 的 Cajal-Retzius 和非 Cajal-Retzius 细胞中,但不定位于突触前结构。我们的结果表明,内源性牛磺酸的活动依赖性非突触释放通过激活 MZ 中的甘氨酸受体来促进兴奋性神经传递。
In the developing cerebral cortex, the marginal zone (MZ), consisting of early-generated neurons such as Cajal-Retzius cells, plays an important role in cell migration and lamination. There is accumulating evidence of widespread excitatory neurotransmission mediated by γ-aminobutyric acid (GABA) in the MZ. Cajal-Retzius cells express not only GABAA receptors but also α2/β subunits of glycine receptors, and exhibit glycine receptor-mediated depolarization due to high [Cl−]i. However, the physiological roles of glycine receptors and their endogenous agonists during neurotransmission in the MZ are yet to be elucidated. To address this question, we performed optical imaging from the MZ using the voltage-sensitive dye JPW1114 on tangential neocortical slices of neonatal rats. A single electrical stimulus evoked an action-potential-dependent optical signal that spread radially over the MZ. The amplitude of the signal was not affected by glutamate receptor blockers, but was suppressed by either GABAA or glycine receptor antagonists. Combined application of both antagonists nearly abolished the signal. Inhibition of Na+, K+-2Cl− cotransporter by 20 µM bumetanide reduced the signal, indicating that this transporter contributes to excitation. Analysis of the interstitial fluid obtained by microdialysis from tangential neocortical slices with high-performance liquid chromatography revealed that GABA and taurine, but not glycine or glutamate, were released in the MZ in response to the electrical stimulation. The ambient release of taurine was reduced by the addition of a voltage-sensitive Na+ channel blocker. Immunohistochemistry and immunoelectron microscopy indicated that taurine was stored both in Cajal-Retzius and non-Cajal-Retzius cells in the MZ, but was not localized in presynaptic structures. Our results suggest that activity-dependent non-synaptic release of endogenous taurine facilitates excitatory neurotransmission through activation of glycine receptors in the MZ.
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