Calcium, proliferation and AMPA receptors in NG2 glial cells

中枢神经系统的正常功能需要神经元集合活动的精确定时。只有当由所谓的髓鞘提供的神经元过程的电隔离加速单个脉冲的传导时，才能实现远程神经元活动的精确定时。重要的是，髓鞘不能由神经元本身产生，而是通过神经元突起、轴突和一种特殊类型的神经胶质细胞、少突胶质细胞之间复杂的、尚未完全理解的相互作用产生的。在发育过程中，少突胶质细胞必须以所需的数量产生，以匹配存在的轴突数量，并且它们必须识别并接触紧邻的轴突。此外，已知轴突的电活动支持少突胶质细胞的产生并加速髓鞘的产生。然而，目前尚不清楚少突胶质细胞如何感知轴突的电活动。我们以前的工作表明，神经突能够释放神经递质到少突胶质细胞的前体细胞上。此外，从少突胶质细胞前体细胞中去除所需的神经递质受体导致分裂速率下降。在这里，我们将测试的假设，即从神经突释放的递质导致少突胶质细胞前体细胞中的钙信号，从而控制其增殖。为此，我们已经开发和验证了一个专用的转基因小鼠模型，我们将测试我们的假设，在一个损失和获得的功能分析的基础上，电生理和细胞生物学技术。我们希望我们的研究结果将揭示有关少突胶质细胞生成的基本方面，并将提高对慢性脱髓鞘疾病的理解和治疗。

Proper function of the central nervous system requires precise timing of the activity of neuron ensembles. Precise timing of the activity of remote neurons can only be achieved if electrical isolation of neuronal processes, provided by so called myelin sheathes, accelerates the conduction of single impulses. Importantly, myelin sheathes cannot be produced by neurons themselves but they arise through an intricate, not well understood interaction between neuronal processes, the axons, and a specialized type of glial cells, the oligodendrocytes. During development oligodendrocytes have to be generated in the required number to match the number of axons present and they have to recognize and contact axons in their immediate vicinity. Furthermore, it is known that electrical activity of axons supports the generation of oligodendrocytes and accelerates the production of myelin sheathes. However, it is currently unclear how oligodendroglial cells may sense the electrical activity of axons. Our previous work demonstrated that neurites are able to release neurotransmitter onto precursor cells of oligodendrocytes. Further, removal of the required neurotransmitter receptor from oligodendrocyte precursor cells lead to a drop in the division rate. Here we will test the hypothesis that transmitter release from neurites causes calcium signals in oligodendrocyte precursor cells which in turn controls their proliferation. To this end we have developed and verified a dedicated transgenic mouse model with which we will test our hypothesis in a loss- and gain-of-function analysis based on electrophysiological and cell biological techniques. We expect that our results will shed light on fundamental aspects regarding the generation of oligodendrocytes and that they will improve the understanding and treatment of chronic demyelinating disorders.