Transmitter-mediated interactions between neurons and astrocytes

神经元和星形胶质细胞之间递质介导的相互作用

• 批准号: 7420947
• 负责人: CRAIG E JAHR
• 金额: $ 16.84万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420947
• 关键词: Acute; Address; Agonist; Astrocytes; CNS processing; Calcium; Cell Count; Cell physiology; Cerebellar cortex structure; Cerebellum; Chromosome Pairing; Communication; Complex; Computer information processing; Condition; Dendritic Spines; Disease; Disruption; Drops; Electrophysiology (science); Electroporation; Elevation; Extracellular Space; Functional Magnetic Resonance Imaging; Gated Ion Channel; Glutamate Transporter; Glutamates; Hippocampus (Brain); Hormonal; Image; Kinetics; Laser Scanning Microscopy; Left; Major Depressive Disorder; Measurement; Measures; Mediating; Membrane; Metabolic; Metabolic Clearance Rate; Microscopy; Monitor; Mus; Neuroglia; Neuronal Plasticity; Neurons; Optics; Pathway interactions; Photons; Physiology; Play; Process; Proteins; Psyche structure; Purkinje Cells; Purpose; Rate; Receptor Activation; Receptor Inhibition; Regulation; Research; Risk; Role; Schizophrenia; Services; Signal Transduction; Slice; Speed; Staging; Synapses; Synaptic Transmission; Techniques; Testing; Thinking; Tube; Whole-Cell Recordings; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; amino 3 hydroxy 5 methylisoxazole 4 propionate; cell motility; density; flash photolysis; in utero; interest; migration; neurological pathology; neurotransmitter release; photolysis; receptor; research study; response; size; synaptic function; synaptogenesis; transmission process; two-photon; uptake

DESCRIPTION (provided by applicant): Astrocytes throughout the CNS provide an array of services for their neighboring neurons including removing transmitters following release and providing metabolic sustenance. The realization that astrocytes are not merely caretakers but are also intimately involved in the main purpose of the CNS, processing information, is recent. Although the responses of astrocytes cannot match the speed of neurons, they can alter the interactions between neurons by isolating or opening pathways of communication between adjacent synapses. Additionally, astrocytes communicate between themselves and, bi-directionally, with neurons by responding to alterations in ionic gradients, released neurotransmitters, and by releasing neuroactive substances. The aim of the present research is to determine the ability of, and mechanisms by which, astrocytes alter the isolation of synapses from neighboring synapses by the extension and retraction of astrocytic lamellipodial processes. These objectives will be addressed using a combination of 2 photon microscopy to directly observe process elaboration, electrophysiology to measure synaptic strength, pharmacological manipulation of receptor activity, 2 photon photolysis of caged glutamate to rapidly activate receptors in dendritic spine-sized volumes, flash photolysis of intracellular caged calcium, and expression of normally absence glutamate- gated ion channels to alter calcium influx. These studies will uncover strategies to control the necessary but potentially damaging effects of releasing glutamate into the extracellular space. Disruption of glutamate clearance followed by excitotoxic damage has been implicated in a variety of neurological pathologies. In addition, in schizophrenia and major depression, glial cell number is subnormal suggesting diminished trophic support of neurons that likely contributes to the reduced neuronal size, density of dendritic spines, and levels of synaptic proteins, as well as the abnormalities observed in fMRI in these conditions. Understanding astrocyte plasticity and its role in synaptic function promises unique approaches to managing the abnormalities in transmission in mental disease.

描述（由申请人提供）：整个中枢神经系统中的星形胶质细胞为其邻近的神经元提供了一系列服务，包括释放后删除发射机并提供代谢寄生。最近的认识是，星形胶质细胞不仅是看护人，而且还密切参与了CNS的主要目的，即处理信息。尽管星形胶质细胞的反应无法匹配神经元的速度，但它们可以通过隔离或开放相邻突触之间的通信途径来改变神经元之间的相互作用。此外，星形胶质细胞通过对离子梯度的改变，释放神经递质的变化以及释放神经活性物质的改变，与神经元之间进行交流。本研究的目的是确定星形胶质细胞的能力和机制，通过延伸和缩回星形胶质细胞层状过程，改变了突触从相邻突触中分离出来。将使用2个光子显微镜的组合来解决这些目标，以直接观察过程阐述，测量突触强度的电生理学，对受体活性的药理学操纵，2个对谷氨酸的光溶解的光溶解，以快速激活树枝状刺激性体积和临床的闪光晶状体的闪光含量钙化的晶状体，以快速激活受体。钙涌入。这些研究将发现控制谷氨酸释放到细胞外空间所必需但潜在的破坏作用的策略。谷氨酸清除的破坏随后造成毒性损伤与多种神经病理性有关。此外，在精神分裂症和严重抑郁症中，神经胶质细胞数是亚正常的，表明对神经元的营养支持减少，这可能导致神经元大小，树突状棘的密度降低，突触蛋白的水平以及在这些条件下在FMRI中观察到的异常。了解星形胶质细胞可塑性及​​其在突触功能中的作用有望控制精神疾病传播异常的独特方法。