Calcium, proliferation and AMPA receptors in NG2 glial cells

中枢神经系统的正常功能需要精确的神经元群的活动时间。只有在所谓的髓鞘提供的神经元突起的电隔离加速单个冲动的传导的情况下，才能实现远程神经元活动的精确计时。重要的是，髓鞘不能由神经元本身产生，但它们是通过神经元突起、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、尚未被很好理解的相互作用而产生的。在发育过程中，必须生成所需数量的少突胶质细胞，以匹配存在的轴突数量，并且它们必须识别和接触其附近的轴突。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，神经突起能够向少突胶质细胞的前体细胞释放神经递质。此外，从少突胶质前体细胞中移除所需的神经递质受体会导致分裂率下降。在这里，我们将检验一种假设，即神经突起释放的递质导致少突胶质前体细胞中的钙信号，而少突胶质前体细胞反过来控制其增殖。为此，我们开发并验证了一种专门的转基因小鼠模型，我们将利用该模型在基于电生理和细胞生物学技术的功能丧失和功能获得分析中验证我们的假设。我们期望我们的结果将阐明有关少突胶质细胞生成的基本方面，并将改善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.