Heterogeneity of neuron-NG2 glia synapses matches glial response to regionally diverse neuronal firing behavior.

神经元-NG2 神经胶质突触的异质性与神经胶质对区域不同神经元放电行为的反应相匹配。

• 批准号: 254853848
• 负责人: Professor Dr. Dirk Dietrich
• 金额: --
• 依托单位: Institut für Neuropathologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/254853848?language=en
• 关键词: Heterogeneity; neuron; NG2; glia; synapses

For proper function the brain needs isolation material around nerve fibres called myelin. This myelin is produced by oligodendroglial cells during development. We now know that myelin can also be generated in adult brains in response to training and that myelin is regenerated after demyelinating lesions. Furthermore, recent evidence indicates that the generation of myelin is dependent on the activity of neurons. The finding that neuronal activity also releases transmitter onto oligodendroglial cells has stimulated the idea that neurons not only use synaptic transmitter release to transmit their pattern of activity to other neurons but also to oligodendroglial cells. However, it has remained obscure how neurons may be able to simultaneously signal to both, other neurons and glial cells although they posses only one output compartment, one axon. We propose that neurons adjust their firing pattern to communicate with other neurons but that they specifically adjust their transmission properties to oligodendroglial cells in order alter signalling to glial cells without the need of changing their firing pattern, a kind of ventriloquist function. We will use electrophysiology in brain slices, in vivo gene knockdown, three-dimensional electron microscopy and proteomics to address this question. Showing that modulation of transmission properties to glial cells controls myelination may be essential for future development of novel therapeutic approaches which could specifically target the release machinery to improve recovery in demyelinating diseases.

为了正常的功能，大脑需要围绕神经纤维的隔离材料，称为髓鞘。这种髓鞘是由少突胶质细胞在发育过程中产生的。我们现在知道，髓鞘也可以在成人大脑中产生，以响应训练，髓鞘是再生后脱髓鞘病变。此外，最近的证据表明，髓鞘的产生依赖于神经元的活动。神经元活动也会释放递质到少突胶质细胞上，这一发现激发了神经元不仅使用突触递质释放将其活动模式传递给其他神经元，而且传递给少突胶质细胞的想法。然而，神经元如何能够同时向其他神经元和神经胶质细胞发出信号仍然是不清楚的，尽管它们只有一个输出隔室，一个轴突。我们提出，神经元调整其发射模式与其他神经元进行通信，但他们专门调整其传输特性，以少突胶质细胞，以改变信号，神经胶质细胞，而不需要改变其发射模式，一种口技功能。我们将使用脑切片的电生理学，体内基因敲除，三维电子显微镜和蛋白质组学来解决这个问题。显示神经胶质细胞控制髓鞘形成的传输特性的调制可能是未来开发新的治疗方法所必需的，该方法可以特异性地靶向释放机制以改善脱髓鞘疾病的恢复。