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: 10600036
• 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10600036
• 关键词: Address; Affect; Agonist; Amendment; Anatomy; Antibodies; Area; Astrocytes; Axon; Basal Ganglia; Behavior; Biochemical; Brain; Brain Stem; Cells; Cerebellum; Data; Decision Making; Dorsal; Drug Addiction; Electrophysiology (science); Emotions; Enzymes; Exclusion; Fiber; Fluoro-Gold; 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; Neuroglia; Neurons; Neurotransmitters; Pain; Pathway interactions; Phenotype; Play; Population; Property; Prosencephalon; Proteins; Regulation; Reporter; Research; Rewards; Role; Sensory; Slice; Spinal Cord; Spinal Ganglia; Structure; Substantia nigra structure; Synapses; Synaptic Receptors; Testing; Thalamic structure; Tracer; Transgenic Mice; Transgenic Organisms; Viral Vector; Vision; Western Blotting; antagonist; 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 excitability; neurotransmission; novel; pars compacta; particle; patch clamp; pharmacologic; postsynaptic; postsynaptic neurons; presynaptic neurons; promoter; 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.

CNS 利用 GABA 和甘氨酸作为两种主要的抑制性神经递质来调节 神经元的兴奋性并调节人体的许多功能。虽然位置和 GABA 神经元的功能已得到相对充分的研究，甘氨酸能神经元的解剖位置 神经元仍然不明确。在这项研究中，我们对基底神经节感兴趣，它是大脑的一部分 调节涉及认知功能的运动运动和反应启动的区域 例如情绪、视觉、某些形式的记忆，并受到毒瘾的严重影响。 在基底节的不同结构中，GP富含GABA能神经 通过纹状体苍白球通路调节自主运动活动的终端 与丘脑的连接并且显然缺乏甘氨酸输入。在目前的研究中， 我们使用多种遗传和生化方法来证明甘氨酸的存在 基底神经节内的神经元。我们的数据提供了一种新型抑制性甘氨酸的证据 电路，其中细胞体定位于黑质致密部 (SNc) 和 投射沿着内侧前脑束移动，最终支配 GP。这些甘氨酸 神经元对 GAD67 和 NeuN 显示出免疫反应性，表明 GABA/甘氨酸双重存在 表型。蛋白质印迹分析、免疫组织化学和电生理学分析 证明 GP 中存在甘氨酸受体并确认其抑制性质 这些突触。该应用将揭示这些黑苍白球甘氨酸纤维在 特定基底神经节调节行为的控制。

项目成果

Identification of amacrine neurons with a glycinergic and GABAergic phenotype in the mouse retina.

• DOI: 10.18103/mra.v10i1.2624
• 发表时间: 2022-01
• 期刊: Medical research archives
• 作者: J. Pérez-León;Annie Espinal-Centeno;Zelene Mendoza-Gonzalez;Alejandra Camacho;A. Lopez;Rosa Perez;M. Miranda