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The role of P2Y1 and AMPA receptors in astrocyte plasticity

P2Y1和AMPA受体在星形胶质细胞可塑性中的作用

基本信息

批准号：
279354007
负责人：
Professor Dr. Christian Lohr
金额：
--
依托单位：
Abteilung Neurophysiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/279354007?language=en
关键词：
role P2Y1 AMPA receptors astrocyte

项目摘要

Perisynaptic astrocytes sense neurotransmitters released from presynaptic terminals and respond with calcium signalling by activation of a multitude of receptors such metabotropic and ionotropic glutamate receptors as well as purinoceptors. Calcium signalling in astrocytes triggers the release of gliotransmitters which are supposed to be involved in synaptic plasticity. In the proposed project we aim to elucidate the contribution of astrocytic glutamatergic and purinergic receptors to the spatio-temporal pattern of astrocyte calcium signalling and to astrocyte plasticity. We hypothesis that: a) Metabotropic and ionotropic glutamate receptors as well as P2Y1 purinoceptors mediate different patterns of local and global calcium signalling in astrocytes, b) Neuron-astrocyte signalling undergoes synaptic plasticity upon tetanic stimulation. To address these hypotheses, we employ transgenic mice carrying astrocyte-specific deletion of AMPA and P2Y1 receptors, respectively. We combine these astrocyte-specific transgenes with laser-guided stimulation techniques such as photoactivation of caged calcium and IP3, respectively, to assess the effect of astrocyte-specific stimulation on astrocyte plasticity and neuronal performance. We use the mouse olfactory bulb as model system, because the olfactory bulb can be used as a whole, i.e. with intact neuronal circuits in contrast to brain slices of, e.g., the hippocampus. In addition, the olfactory bulb contains cell body-free synaptic domains in so-called glomeruli, invaded by clearly visible astrocyte processes, rendering the system ideal for imaging studies on astrocytes. The results will broaden our understanding how astrocytes are implemented in neuronal networks and influence neuronal performance such as odour perception. They will demonstrate that astrocytes are by no means passive elements of the brain serving solely homeostatic functions, but significantly contribute to information processing and hence brain function.

突触周星形胶质细胞感知突触前末梢释放的神经递质，并通过激活多种受体如代谢型和离子型谷氨酸受体以及嘌呤受体来响应钙信号传导。星形胶质细胞中的钙信号触发了胶质递质的释放，胶质递质被认为与突触可塑性有关。在拟议的项目中，我们的目标是阐明星形胶质细胞的钙和嘌呤受体的时空格局的星形胶质细胞的钙信号和星形胶质细胞的可塑性的贡献。我们假设：a）代谢型和离子型谷氨酸受体以及P2 Y1嘌呤受体介导星形胶质细胞中局部和整体钙信号传导的不同模式。B）神经元-星形胶质细胞信号传导在强直刺激后经历突触可塑性。为了解决这些假设，我们采用转基因小鼠携带星形胶质细胞特异性缺失AMPA和P2 Y1受体，分别。我们将联合收割机这些星形胶质细胞特异性转基因与激光引导的刺激技术如笼状钙和IP 3的光活化分别结合，以评估星形胶质细胞特异性刺激对星形胶质细胞可塑性和神经元性能的影响。我们使用小鼠嗅球作为模型系统，因为嗅球可以作为一个整体使用，即与脑切片相比，具有完整的神经元回路，例如，海马体此外，嗅球在所谓的肾小球中含有无细胞体的突触结构域，被清晰可见的星形胶质细胞过程侵入，使得该系统非常适合星形胶质细胞的成像研究。这些结果将拓宽我们对星形胶质细胞如何在神经元网络中实现并影响气味感知等神经元性能的理解。他们将证明星形胶质细胞绝不是大脑的被动元件，只提供稳态功能，但对信息处理和大脑功能有重要贡献。