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首页> 外文期刊>The European Journal of Neuroscience >Syntaxin 1B contributes to regulation of the dopaminergic system through GABA transmission in the CNS
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Syntaxin 1B contributes to regulation of the dopaminergic system through GABA transmission in the CNS

机译：Syntaxin 1b通过CNS中的GABA传输有助于调节多巴胺能系统

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Abstract In neuronal plasma membrane, two syntaxin isoforms, HPC1/syntaxin 1A (STX1A) and syntaxin 1B (STX1B), are predominantly expressed as solubleN ethylmaleimidesensitive fusion attachment protein receptors, also known as tSNAREs. We previously reported that glutamatergic and GABAergic synaptic transmissions are impaired in Stx1b null mutant (Stx1b / ) mice but are almost normal in Stx1a null mutant (Stx1a / ) mice. These observations suggested that STX1A and STX1B have distinct functions in fast synaptic transmission in the central nervous system (CNS). Interestingly, recent studies indicated thatStx1a / orStx1a +/ mice exhibit disruption in the monoaminergic system in the CNS, causing unusual behaviour that is similar to neuropsychological alterations observed in psychiatric patients. Here, we studied whether STX1B contributes to the regulation of monoaminergic system and ifSTX1B is related to neuropsychological properties in human neuropsychological disorders similar toSTX1A . We found that monoamine releaseinitro was normal inStx1b +/ mice unlikeStx1a / orStx1a +/ mice, but the basal extracellular dopamine (DA) concentration in the ventral striatum was increased. DA secretion in the ventral striatum is regulated by GABAergic neurons, andStx1b +/ mice exhibited reduced GABA release bothinitro andinivo , disrupting the DAergic system in the CNS of these mice. We also found thatStx1b +/ mice exhibited reduced prepulse inhibition (PPI), which is believed to represent one of the prominent schizotypal behavioural profiles of human psychiatric patients. The reduction in PPI was rescued by DA receptor antagonists. These observations indicated thatSTX1B contributes to excess activity of the DAergic system through regulation of GABAergic transmission.
机译：摘要在神经元膜膜中，两个语法同种型，HPC1 /语法1a（STX1a）和语法1b（STX1b）主要表达为Solublen乙基乙酰胺酰亚胺酰亚胺封闭蛋白受体，也称为TSNARES。我们以前报道，在STX1B NULL突变体（STX1B /）小鼠中，谷氨酸和GABAIGIC突触透射效果损害，但在STX1A空突变体（STX1A /）小鼠中几乎是正常的。这些观察结果表明，STX1A和STX1B在中枢神经系统（CNS）中的快速突触传递中具有不同的功能。有趣的是，最近的研究表明，ASTX1A / ORSTX1A + /小鼠表现出CNS中单氨基能系统中的破坏，导致类似于在精神病患者中观察到的神经心理学改变的异常行为。在这里，我们研究了STX1B是否有助于调节单氨基能系统，IFSTX1B与人类神经心理学疾病中的神经心理学性质类似的TOSTX1a有关。我们发现单胺脱氨酸钛腈是正常的INSCRX1B + /小鼠Ullikex1a / Orstx1a + /小鼠，但腹侧纹状体中的基底细胞外多巴胺（DA）浓度增加。腹侧纹状体中的DA分泌由甘草神经元调节，Andstx1b + /小鼠表现出降低的GABA释放Bothinitro和inInvo，破坏了这些小鼠的CNS中的晚期系统。我们还发现，TheStX1B + /小鼠表现出降低的预脉冲抑制（PPI），其被认为代表人精神病患者的突出酶行为谱之一。通过DA受体拮抗剂拯救了PPI的还原。这些观察结果表明，ASTX1B通过调节加巴能传输来有助于治疗后的过度活性。

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