Novel Glycinergic Circuitry in the Basal Ganglia

中枢神经系统利用GABA和甘氨酸作为两种主要的抑制性神经递质来调节 神经元的兴奋性和调节人体的许多功能。虽然地点和 对GABA神经元的功能研究相对较多，甘氨酸能神经元的解剖定位 神经元的定义仍然很模糊。在这项研究中，我们感兴趣的是基底神经节，即大脑 调节运动启动和涉及认知功能的反应的区域 如情绪、视觉、某些形式的记忆，并在药物成瘾中受到严重影响。 在基底神经节的不同结构中，GP丰富于GABA能神经 通过纹状体旁路调节自主运动活动的终末和 与丘脑有联系，显然没有甘氨酸能输入。在本研究中， 我们使用几种遗传和生化方法来证明甘氨酸能的存在。 基底节内的神经元。我们的数据为一种新的抑制性甘氨酸能提供了证据 环路，胞体定位于黑质致密部(SNC) 沿着内侧前脑束移动的投射最终支配GP。这些甘氨酸能 神经元对GAD67和NeuN呈免疫反应性，提示存在双重的GABA/甘氨酸 表型。蛋白质印迹分析、免疫组织化学和电生理分析 证明甘氨酸受体在糖蛋白中的存在，并确认其对 这些突触。这一应用将揭示这些黑质苍白质甘氨酸能纤维在 对特定基底节的控制调节了行为。

The CNS utilize GABA and glycine as the two main inhibitory neurotransmitters to modulate neuronal excitability and regulate many functions of the human body. Although the location and function of GABA neurons is relatively well studied, the anatomical location of glycinergic neurons remains poorly-defined. In this study, we are interested in the basal ganglia, a brain area that regulate initiation of motor movements and responses that involves cognitive functions such as emotion, vision, some forms of memory and is heavily affected in drug addiction. Among the different structures of the basal ganglia, the GP is enriched in GABAergic nerve terminals that regulate voluntary locomotor activity via the striatopallidal pathway and connections with the thalamus and apparently devoid of glycinergic inputs. In the present study, we use several genetic and biochemical approaches to demonstrate the presence of glycinergic neurons within the basal ganglia. Our data provide evidence of a novel inhibitory glycinergic circuit, where the cell bodies are localized to the substantia nigra pars compacta (SNc) and projections moving along the medial forebrain bundle to finally innervate GP. These glycinergic neurons showed immune-reactivity for GAD67 and NeuN, suggesting a dual GABA/Glycine phenotype. Western blot analysis, immunohistochemistry and electrophysiology analysis demonstrate the presence of the glycine receptor in the GP and confirm the inhibitory nature on these synapses. This application will reveal the role of these nigropallidal glycinergic fibers in the control of specific basal-ganglia regulated behaviors.