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

为了正常运作，大脑需要一种被称为髓鞘的神经纤维周围的隔离材料。这种髓鞘是由发育过程中的少突胶质细胞产生的。我们现在知道，髓鞘也可以在成人大脑中产生，作为对训练的反应，脱髓鞘损伤后髓鞘可以再生。此外，最近的证据表明，髓鞘的产生依赖于神经元的活动。神经元活动也向少突胶质细胞释放递质的发现激发了这样的想法，即神经元不仅利用突触递质释放将其活动模式传递给其他神经元，而且还传递给少突胶质细胞。然而，尽管神经元只有一个输出室，一个轴突，但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不清楚。我们建议神经元调整其放电模式以与其他神经元交流，但它们特异性地调整其向少突胶质细胞的传递特性，以便在不需要改变其放电模式的情况下改变向神经胶质细胞的信号传递，这是一种腹语功能。我们将使用脑片的电生理学、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。表明调节神经胶质细胞的传递特性控制髓鞘形成可能对未来开发新的治疗方法至关重要，这种方法可以专门针对释放机制来改善脱髓鞘疾病的恢复。

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.