Novel Glycinergic Circuitry in the Basal Ganglia

基底神经节中的新型甘氨酸能回路

• 批准号: 10381670
• 负责人: Manuel Miranda-Arango
• 金额: $ 30.2万
• 依托单位: UNIVERSITY OF TEXAS EL PASO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381670
• 关键词: Address; Affect; Agonist; Anatomy; Antibodies; Architecture; Area; Astrocytes; Axon; Basal Ganglia; Behavior; Biochemical; Brain; Brain Stem; Cells; Cerebellum; Data; Decision Making; Dorsal; Drug Addiction; Electrophysiology (science); Emotions; Enzymes; Fiber; GABA Receptor; Generations; Genetic; Genetic Vectors; Globus Pallidus; Glutamate Decarboxylase; Glycine; Glycine Receptors; Human; Human body; Hypothalamic structure; Immune; Immunohistochemistry; Injections; Knowledge; Label; Light; Location; Memory; Motor; Motor Activity; Motor Cortex; Movement; Mus; Nature; Nerve; Nervous system structure; Neuroglia; Neurons; Neurotransmitters; Pain; Pathway interactions; Pharmacology; Phenotype; Play; Population; Prosencephalon; Proteins; Regulation; Reporter; Research; Rewards; Role; Sensory; Slice; Spinal Cord; Spinal Ganglia; Structure; Subcellular Anatomy; Substantia nigra structure; Synapses; Testing; Thalamic structure; Tracer; Transgenic Mice; Transgenic Organisms; Viral Vector; Vision; Western Blotting; Wild Type Mouse; antagonist; base; behavior test; biophysical properties; cell type; cognitive function; electrical property; extracellular; gamma-Aminobutyric Acid; glycine transporter; hindbrain; immunoreactivity; in vivo; interest; median forebrain bundle; motor disorder; motor learning; neural circuit; neuronal cell body; neuronal excitability; neurotransmission; novel; pars compacta; particle; patch clamp; postsynaptic; postsynaptic neurons; promoter; receptor; response; somatosensory; transmission process

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.

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。虽然位置和 GABA神经元的功能研究得相对较好，甘氨酸能神经元的解剖学位置 神经元仍然不明确。在这项研究中，我们感兴趣的是基底神经节， 调节涉及认知功能的运动和反应的启动的区域 如情感、视觉、某些形式的记忆，并在药物成瘾中受到严重影响。 在基底节的不同结构中，GP在GABA能神经中富集 通过纹状体-苍白球途径调节自主运动活动的终末， 与丘脑的连接，显然缺乏甘氨酸能输入。在本研究中， 我们使用几种遗传和生物化学方法来证明甘氨酸能的存在， 基底神经节内的神经元。我们的数据提供了一种新的抑制甘氨酸能的证据， 回路，其中细胞体位于黑质（SNc）， 投射沿着内侧前脑束移动，最终支配GP。这些甘氨酸能 神经元对GAD 67和NeuN表现出免疫反应性，表明GABA/甘氨酸双 表型蛋白质印迹分析、免疫组织化学和电生理分析 证明GP中存在甘氨酸受体，并证实对 这些突触这项应用将揭示这些黑质苍白球甘氨酸能纤维在 对特定基底神经节调节行为的控制。