GlyT1 determines the glycinergic phenotype of amacrine cells in the mouse retina

GlyT1 determines the glycinergic phenotype of amacrine cells in the mouse retina
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DOI:
10.1007/s00429-018-1684-3
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发表时间:
2018-09-01
影响因子:
3.1
通讯作者:
Brandstaetter, Johann Helmut
Brandstaetter, Johann Helmut
中科院分区:
医学3区
文献类型:
--
作者:
Eulenburg, Volker;Knop, Gabriel;Brandstaetter, Johann Helmut

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甘氨酸是抑制性和兴奋性谷氨酸能突触的神经递质,主要存在于中枢神经系统的尾侧,也存在于额脑和视网膜。在其突触前释放并与尾部甘氨酸能突触的突触后受体结合后,两个高亲和力的甘氨酸转运体GlyT1和GlyT2将甘氨酸从细胞外间隙中移除。甘氨酸能神经元表达GlyT2,这是突触前递质补充所必需的,而胶质细胞表达的GlyT1被证明控制细胞外甘氨酸的浓度。在这里,我们表明,视网膜甘氨酸能无长突细胞表达的GlyT1不仅有助于控制视网膜细胞外甘氨酸的浓度,而且对于维持该细胞群体的甘氨酸能递质表型也是必不可少的。具体地说,甘氨酸能AII无长突细胞GlyT1的丢失损害了AII介导的甘氨酸能神经传递,改变了细胞外甘氨酸浓度的调节,而不改变甘氨酸能突触的总体分布和/或大小。综上所述,我们的结果表明,视网膜中无长突细胞表达的GlyT1在尾部甘氨酸能突触上结合了神经元GlyT2和神经胶质GlyT1所覆盖的功能。
The amino acid glycine acts as a neurotransmitter at both inhibitory glycinergic and excitatory glutamatergic synapses predominantly in caudal regions of the central nervous system but also in frontal brain regions and the retina. After its presynaptic release and binding to postsynaptic receptors at caudal glycinergic synapses, two high-affinity glycine transporters GlyT1 and GlyT2 remove glycine from the extracellular space. Glycinergic neurons express GlyT2, which is essential for the presynaptic replenishment of the transmitter, while glial-expressed GlyT1 was shown to control the extracellular glycine concentration. Here we show that GlyT1 expressed by glycinergic amacrine cells of the retina does not only contribute to the control of the extracellular glycine concentration in the retina but is also essential for the maintenance of the glycinergic transmitter phenotype of this cell population. Specifically, loss of GlyT1 from the glycinergic AII amacrine cells impairs AII-mediated glycinergic neurotransmission and alters regulation of the extracellular glycine concentration, without changes in the overall distribution and/or size of glycinergic synapses. Taken together, our results suggest that GlyT1 expressed by amacrine cells in the retina combines functions covered by neuronal GlyT2 and glial GlyT1 at caudal glycinergic synapses.