Novel Glycinergic Circuitry in the Basal Ganglia

基底神经节中的新型甘氨酸能回路

基本信息

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
项目类别：
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

项目摘要

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和甘氨酸作为两个主要抑制性神经递质调节神经元兴奋性并调节人体的许多功能。虽然位置和 GABA神经元的功能相对很好地研究了甘氨酸能的解剖位置神经元定义不高。在这项研究中，我们对基底神经节感兴趣调节涉及认知功能的运动运动和反应的领域例如情感，视觉，某些形式的记忆，并在吸毒成瘾中受到严重影响。在基底神经节的不同结构中，GP富含GABA能神经通过纹状体式途径调节自愿运动活性的末端与丘脑的连接，显然没有甘体能输入。在目前的研究中，我们使用几种遗传和生化方法来证明存在甘油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型抑制性甘氨酸能的证据电路，将细胞体定位于底底nigra pars comcacta（SNC）和投影沿着内侧前脑束移动，最终支配GP。这些甘氨酸能神经元对GAD67和NEUN显示免疫反应性，表明双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GP中的存在，并确认抑制性质这些突触。该应用将揭示这些斑纹金糖纤维在控制特定基础 - 根基因调节行为的控制。