Glutamatergic transmission within the sensory ganglion

感觉神经节内的谷氨酸传输

基本信息

批准号：
8627218
负责人：
LUC JASMIN
金额：
$ 19.52万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8627218
关键词：
AMPA Receptors Afferent Neurons Appearance Area Astrocytes Behavioral Brain Brain Diseases Caliber Cells Chemicals Chronic low back pain Clinic Visits Communication Data Development Drug Targeting Electron Microscopy Epilepsy Esthesia Event Facial Pain Fibromyalgia Foundations Ganglia Glutamate Agonist Glutamate Receptor Glutamates Headache Immunoelectron Microscopy Injection of therapeutic agent Laboratories Lead Learning Light Microscope Measures Mechanical Stimulation Mediating Membrane Metabotropic Glutamate Receptors Migraine N-Methyl-D-Aspartate Receptors N-Methylaspartate NR1 NMDA receptor Nerve Nervous system structure Neuroglia Neurons Neurotransmitters Nociception Operant Conditioning Pain Pain Clinics Pathology Peripheral Pharmaceutical Preparations Play Rattus Regulation Research Role Schizophrenia Sensory Ganglia Signal Transduction Social Problems Solid Structure of trigeminal ganglion Surface TNF gene Testing Trigeminal System behavior test cell type chronic constriction injury chronic pain experience extracellular ganglion cell immunocytochemistry improved in vivo injured kainate light microscopy metabotropic glutamate receptor 2 metabotropic glutamate receptor 3 metabotropic glutamate receptor 8 nerve injury nerve supply neurochemistry neuronal cell body neuronal excitability neurotransmission novel therapeutic intervention pain behavior painful neuropathy patch clamp public health relevance receptor repository research study transmission process

项目摘要

DESCRIPTION (provided by applicant): For more than 50 years we have known that glutamate is the main excitatory neurotransmitter in the brain but we have much more to learn about the function and regulation of glutamate. Our laboratory intends to elucidate the role of glutamate in sensory ganglia, which is the area of the nervous system where all primary sensory neurons are located. While the importance of the sensory ganglion in transmitting pain signals is undeniable, the function of glutamate in the ganglion has not been studied. Our recent experiments provide evidence that there is a significant release of glutamate in sensory ganglia, where it activates pain neurons. To firmly establish the role of glutamate in the ganglion, it is critical that we show its effects occur through receptors and that there are glutamate related changes in the ganglia following nerve injury. The experiments we propose involve pharmacologic modulation of glutamate receptors on sensory neurons to determine the behavioral effects. We will also use electrophysiological recording from whole, intact ganglia to determine the effects of glutamate on specific receptors in the ganglion. Using electron microscopy, we will also locate the cells in the sensory ganglion that have glutamate receptors on their surface that enables them "see" glutamate. From a scientific point of view these findings will provide a solid foundation for the notion that there is chemical communication (cross-excitation) between sensory neurons through non-synaptic (volume) transmission. This will lead to a comprehensive view of the neurochemical events occurring around sensory neurons. These findings will bring a fresh understanding of the sensory ganglion as a dynamic area where key chemical phenomena are involved in various forms of pain, from migraines, to intractable facial pain, from fibromyalgia to chronic low back pain. The sensory ganglion is an ideal area to study volume transmission, which is now being implicated in brain disorders such as epilepsy and schizophrenia.

描述（由申请人提供）：50 多年来，我们已经知道谷氨酸是大脑中主要的兴奋性神经递质，但对于谷氨酸的功能和调节，我们还有更多的东西需要了解。我们的实验室旨在阐明谷氨酸在感觉神经节中的作用，感觉神经节是神经系统中所有初级感觉神经元所在的区域。虽然感觉神经节在传递疼痛信号方面的重要性是不可否认的，但谷氨酸在神经节中的功能尚未被研究。我们最近的实验提供的证据表明，感觉神经节中谷氨酸大量释放，它激活了疼痛神经元。为了牢固地确定谷氨酸在神经节中的作用，至关重要的是我们要证明其作用是通过受体发生的，并且神经损伤后神经节中存在与谷氨酸相关的变化。我们提出的实验涉及对感觉神经元上谷氨酸受体的药理调节，以确定行为效应。我们还将使用整个完整神经节的电生理记录来确定谷氨酸对神经节中特定受体的影响。使用电子显微镜，我们还将定位感觉神经节中表面具有谷氨酸受体的细胞，使它们能够“看到”谷氨酸。从科学的角度来看，这些发现将为感觉神经元之间通过非突触（体积）传输进行化学通讯（交叉兴奋）的概念提供坚实的基础。这将导致对感觉神经元周围发生的神经化学事件的全面了解。这些发现将使人们对感觉神经节作为一个动态区域产生新的认识，其中关键的化学现象涉及各种形式的疼痛，从偏头痛到顽固性面部疼痛，从纤维肌痛到慢性腰痛。感觉神经节是研究容量传输的理想区域，目前容量传输与癫痫和精神分裂症等脑部疾病有关。