Astrocyte-neuron interaction in behavior driven by striatal information processing

纹状体信息处理驱动的行为中星形胶质细胞-神经元的相互作用

• 批准号: 9153346
• 负责人: Alfonso Araque
• 金额: $ 45.91万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9153346
• 关键词: Acute; Affect; Animal Behavior; Area; Astrocytes; Automation; Basal Ganglia; Behavior; Behavioral; Biological Neural Networks; Brain; Brain Diseases; Calcium; Cells; Characteristics; Communication; Complex; Corpus striatum structure; Development; Disease; Dorsal; Electrophysiology (science); Elements; Funding; Future; Generations; Gilles de la Tourette syndrome; Grant; Hippocampus (Brain); Huntington Disease; Image; In Situ; In Vitro; Interneurons; Laboratories; Learning; Long-Term Potentiation; Maintenance; Memory; Mental Depression; Microscopy; Neurons; Neurotransmitters; Obsessive-Compulsive Disorder; Organism; Parkinson Disease; Pathway interactions; Performance; Play; Property; Regulatory Element; Retina; Role; Signal Transduction; Slice; Synapses; Synaptic Transmission; Synaptic plasticity; System; Task Performances; Techniques; Testing; Therapeutic; Transgenic Mice; United States National Institutes of Health; abstracting; addiction; behavioral study; cellular targeting; designer receptors exclusively activated by designer drugs; driving behavior; graduate student; habit learning; in vivo; information processing; insight; neural information processing; neuronal circuitry; novel; operation; optogenetics; synaptic function; tool; two-photon

7. Project Summary/Abstract Studies on synaptic plasticity underlying learning and memory have mainly focused on neuronal elements. However, astrocytes, classically considered as merely supportive cells, are emerging as key regulatory elements potentially involved in learning, memory, and neural information processing because they respond to neurotransmitters and modulate neuronal activity and synaptic function through the release of gliotransmitters. While important progress has been made to define the cellular mechanisms underlying astrocyte modulation of synaptic function in certain brain areas, such as hippocampus, retina and cortex, exactly what specific roles astrocytes play in the neural information processing system remains largely unknown. We have recently found that neuronal activity in the dorsal striatum elevates astrocyte Ca2+ levels, which, in turn, impact striatal neuronal activity and synaptic transmission. Yet, fundamental questions remain unknown, such as the astrocyte contribution to synaptic plasticity, to neural network information processing, and to the consequences on animal behavior. The present proposal aims to define the impact of striatal astrocyte activity on corticostriatal synaptic transmission and plasticity, striatal neural network activity and striatum-related behavioral task performance. We hypothesize that astrocyte activity controls synaptic function and plasticity, and influences neural network operation and animal behavior. To test this hypothesis we will combine in situ and in vivo approaches and state-of-the-art techniques, including optogenetics, pharmacogentics (“designer receptors exclusively activated by designer drugs”, DREADD), simultaneous two-photon microscopy Ca2+ imaging and multiple electrophysiological recordings, novel transgenic mice, in vivo electrophysiological recordings, and specific behavior studies. For this purpose, the proposal brings together two laboratories with complimentary expertise – the Araque lab with expertise in astrocyte-neuron interactions in in vitro slices at cellular level and the Redish lab with expertise in striatal neuronal information processing and behavior at circuit and organism levels, that are already collaborating successfully, including co-advising a graduate student funded by a F30 NIH grant. The expected results will define the role of astrocytes in the striatal function and the consequent animal behavior, which will help to identify novel cellular mechanisms underlying brain function. Defining these roles of astrocytes on synaptic plasticity, network operation and animal behavior will reveal novel mechanisms involved in brain disorders occurring in certain brain diseases, such Parkinson´s and Huntington`s diseases, Obsessive Compulsive Disorder, Tourette's syndrome, and addiction, which may serve to identify novel cellular targets to develop future therapeutic strategies.

7。项目摘要/摘要 关于学习和记忆的合成可塑性的研究主要集中在神经元元素上。 但是，星形胶质细胞（通常被视为支持性细胞）正在成为关键调节 可能涉及学习，记忆和神经信息处理的要素，因为它们会做出回应 神经递质并通过释放神经胶镜来调节神经元活性和突触功能。 尽管已经取得了重要进展来定义星形胶质细胞调制的细胞机制 某些大脑区域的突触功能，例如海马，视网膜和皮层，正是什么特定角色 星形胶质细胞在神经信息处理系统中发挥作用，在很大程度上未知。我们最近发现 背纹状体中的神经元活性升高了星形胶质细胞Ca2+水平，进而影响纹状体 神经元活动和突触传播。然而，基本问题仍然未知，例如 星形胶质细胞对突触可塑性，神经网络信息处理以及后果的贡献 关于动物行为。目前的建议旨在定义纹状体星形胶质细胞活动对 皮质纹状体突触传递和可塑性，纹状体神经网络活动以及纹状体相关 行为任务表现。我们假设星形胶质细胞活性控制着突触功能和可塑性， 并影响神经网络的操作和动物行为。 为了检验这一假设，我们将结合原位和体内方法和最先进的技术，包括 光遗传学，药物（“设计器受体专门由设计师药物激活”，Dreadd）， 同时两光子显微镜CA2+成像和多个电生理记录，新颖 转基因小鼠，体内电生理记录和特定行为研究。为此， 提案汇集了两个具有免费专业知识的实验室 - 具有专业知识的Araque实验室 星形胶质细胞 - 神经元相互作用在细胞水平上的体外切片和具有纹状体专业知识的Redish Lab 在电路和生物级别的神经元信息处理和行为，这些信息已经在协作 成功地，包括共同努力由F30 NIH赠款资助的研究生。 预期的结果将定义星形胶质细胞在纹状体功能中的作用和随之而来的动物 行为，这将有助于确定大脑功能的新型细胞机制。定义这些角色 关于突触可塑性，网络操作和动物行为的星形胶质细胞将揭示涉及的新机制 在某些脑部疾病中发生的脑部疾病，例如帕金森氏症和亨廷顿疾病 强迫症，图雷特综合征和成瘾，可能有助于识别新颖的细胞靶标 制定未来的治疗策略。