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.项目总结/摘要 学习记忆中突触可塑性的研究主要集中在神经元成分上。 然而，星形胶质细胞，传统上被认为是仅仅支持细胞，正在成为关键的调节细胞。 可能参与学习、记忆和神经信息处理的元素，因为它们对 神经递质的作用，并通过释放胶质递质调节神经元活动和突触功能。 虽然在确定星形胶质细胞调节的细胞机制方面已经取得了重要进展， 突触功能在大脑的某些区域，如海马、视网膜和皮层，究竟起着什么样的具体作用 星形胶质细胞在神经信息处理系统中的作用仍然是未知的。我们最近发现 背侧纹状体的神经元活动会提高星形胶质细胞的Ca 2+水平，从而影响纹状体的 神经元活动和突触传递。然而，根本问题仍然未知，例如 星形胶质细胞对突触可塑性、神经网络信息处理和后果的贡献 关于动物行为。目前的建议旨在确定纹状体星形胶质细胞活性对 皮质纹状体突触传递和可塑性，纹状体神经网络活动和纹状体相关 行为任务绩效我们假设星形胶质细胞的活动控制着突触的功能和可塑性， 并影响神经网络运作和动物行为。 为了验证这一假设，我们将结合联合收割机原位和体内方法以及最先进的技术，包括 光遗传学，药物遗传学（“设计师受体专门由设计师药物激活”，DREADD）， 同时双光子显微镜Ca 2+成像和多种电生理记录，新的 转基因小鼠、体内电生理记录和特定行为研究。为此所述 该提案汇集了两个具有互补专业知识的实验室-Araque实验室， 在细胞水平上体外切片中星形胶质细胞-神经元相互作用和具有纹状体专长的Redish实验室 神经元的信息处理和行为在电路和有机体水平上， 成功地，包括共同建议由F30 NIH赠款资助的研究生。 预期的结果将确定星形胶质细胞在纹状体功能中的作用，以及随后的动物模型。 行为，这将有助于识别大脑功能的新细胞机制。定义这些角色 星形胶质细胞对突触可塑性、网络运作和动物行为的影响将揭示新的机制 在某些脑部疾病中发生的脑部紊乱，如帕金森病和亨廷顿病，强迫症 强迫症，图雷特综合征和成瘾，这可能有助于确定新的细胞靶点， 制定未来的治疗策略。