Regulation of Glycine Neurotransmission by the Glial Glycine Transporter 1.

神经递质转运蛋白对于突触传递的快速终止至关重要，并且构成不同广泛处方药物的重要靶标。神经胶质甘氨酸转运蛋白1（GlyT 1）被认为在抑制性甘氨酸能受体和兴奋性N-甲基-D-天冬氨酸（NMDA）受体介导的神经传递的调节中具有重要作用。此外，它构成了精神分裂症药物开发的重要目标。GlyT 1基因的敲除由于过度抑制呼吸节律发生而导致小鼠出生后早期死亡。在这里，我们建议研究GlyT 1在成人中枢神经系统中的功能，通过使用小鼠品系，其中要么只包含一个单一的活性GlyT 1等位基因或表达增加的水平的神经胶质细胞中的转运蛋白，由于Cre/lox驱动激活沉默GlyT 1转基因。这些小鼠的生化，免疫细胞化学，电生理和行为分析将被用来揭示GlyT 1在抑制性和兴奋性突触的具体作用。此外，所提出的工作可能有助于产生精神分裂症的动物模型。

Neurotransmitter transporters are crucial for the rapid termination of synaptic transmission and constitute important targets of different widely prescribed drugs. The glial glycine transporter 1 (GlyT1) is thought to have important roles in the regulation of both inhibitory glycinergic and excitatory N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. In addition, it constitutes an important target in medication development for schizophrenia. Knockout of the GlyT1 gene causes early postnatal lethality in mice due to over-inhibition of respiratory rhythmogenesis. Here, we propose to study the functions of GlyT1 in the adult CNS by using mouse lines which either contain only a single active GlyT1 allele or express increased levels of the transporter in glial cells, due to Cre/lox driven activation of a silent GlyT1 transgene. Biochemical, immunocytochemical, electrophysiological and behavioural analyses of such mice will be used to disclose the specific roles of GlyT1 at inhibitory and excitatory synapses. In addition, the work proposed may help to generate animal models of schizophrenia.