Astrocytic regulation of neuronal synchronization

星形胶质细胞对神经元同步的调节

基本信息

批准号：
8608511
负责人：
RAFAEL YUSTE
金额：
$ 20万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
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：
2013-02-01 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8608511
关键词：
Action Potentials Astrocytes Biological Assay Brain Buffers Calcium Cerebral cortex Disease Electrophysiology (science)Functional Magnetic Resonance Imaging Gap Junctions Generations Genetic Genetic Techniques Giant Cells Glutamates Goals Housekeeping Image In Vitro Individual Injection of therapeutic agent Label Lead Light Link Methods Mus Neuroglia Neurons Neurosciences Neurotransmitters Optics Outcome Output Pattern Play Population Process Recurrence Recycling Regulation Research Rest Role Sensory Series Shapes Signal Transduction Slice Slow-Wave Sleep Synapses Synaptic Transmission Testing Therapeutic Transgenic Organisms Work awake cell type extracellular in vivo information processing member mental state neocortical neural circuit neuronal patterning novel novel strategies operation photoactivation public health relevance research study skills spatiotemporal tool two-photon

项目摘要

DESCRIPTION (provided by applicant): Astrocytic regulation of neuronal synchronization. The function that astrocytic glia play is poorly understood, and their traditional role, as supportive of neurons, captures only a small part of many functional outputs that astrocytes may have. Recent research on astrocytes has revealed important effects on synaptic transmission, but their role in the circuit as a whole has been less studied, partly due to lack of circuit-level assays of the interaction between astrocytes and neurons. Using two-photon imaging, we have recently discovered that, in neocortical brain slices, stimulation of a single astrocyte can lead t widespread neuronal synchronization, in the form of UP states. Conversely, blocking astrocytic signaling by the injection of BAPTA into individual astrocytes can reduce the number of spontaneous neuronal UP states. We propose to test in a series of direct experiments if astrocytes regulate UP states in vivo. We have developed new two-photon and genetic techniques that enable us to image and manipulate the activity of astrocytes in vivo and examine how it relates to neuronal UP states. Our central hypothesis is that the activity of astrocytes precedes, and is causally related, to the occurrence of UP states. Specifically, in a first aim we will perform fast two-photon calcium imaging, with SLMs, of neuronal and astrocytic activity during UP states in Brainbow mice where astrocytic territories are labeled, and examine whether there are spatio- temporal correlations between the activity of astrocytes and neurons. In a second aim we will optically stimulate astrocytes, using two-photon uncaging of RuBi- glutamate, IP3 or ChR2 photoactivation, and test whether this increases or alters spontaneous UP states. Our proposed work could establish a causal link between astrocytic function and neuronal synchronization in vivo, thus providing a novel circuit-level functional role for astrocytes. UP states are thought to underlie slow-wave sleep and "resting state" fMRI signals, so our research could directly involve astrocytes in the circuit mechanisms of those global brain states. Our group has a unique combination of optical and circuit neuroscience skills and this research could introduce novel approaches into the study of astroglia.

描述（由申请人提供）：神经元同步的星形细胞调节。星形胶质胶质发挥的功能知之甚少，其传统作用是对神经元的支持，仅捕获了星形胶质细胞可能具有的许多功能输出的一小部分。关于星形胶质细胞的最新研究揭示了对突触传播的重要影响，但是它们在整个电路中的作用较少，部分原因是由于缺乏电路级别星形胶质细胞与神经元之间相互作用的测定。使用两光子成像，我们最近发现，在新皮层脑切片中，刺激单个星形胶质细胞可以以UP状态的形式引导T型神经元同步。相反，通过向单个星形胶质细胞注入BAPTA来阻断星形细胞信号传导可以减少自发性神经元向上状态的数量。如果星形胶质细胞在体内调节状态，我们建议在一系列直接实验中进行测试。我们已经开发了新的两光子和遗传技术，使我们能够在体内形象和操纵星形胶质细胞的活性，并检查其与神经元如何相关的状态。我们的中心假设是，星形胶质细胞的活性与UP状态的发生之前相关，并且因果关系。具体而言，在第一个目的中，我们将使用SLM进行快速的两光子钙成像，并在标记星形胶质细胞区域的Brainbow小鼠中使用神经元和星形胶质细胞活性进行神经元和星形胶质细胞活性，并检查星形胶质细胞和神经元的活性之间是否存在时空相关性。在第二个目的中，我们将使用Rubi-谷氨酸，IP3或CHR2光活化的两光子渗透刺激星形胶质细胞，并测试这是否增加还是改变自发状态。我们提出的工作可以在体内建立星形细胞功能与神经元同步之间建立因果关系，从而为星形胶质细胞提供了新型的电路级功能作用。 UP州被认为是慢波睡眠和“静止状态” fMRI信号的基础，因此我们的研究可能直接涉及星形胶质细胞，这是这些全球大脑状态的电路机制。我们的小组具有光学和电路神经科学技能的独特组合，这项研究可以将新颖的方法引入星形胶质细胞研究中。