Neuronal Regulation of NG2 Cells

哺乳动物CMS中的神经胶质细胞负责创造和维持一个环境， 神经元活性可以持续，并且能够调节这种活性。这种密切的相互关系 神经元和非神经元细胞之间的差异表明，可能存在快速调节神经胶质细胞的机制， 反应周围神经元需求变化的行为。我们之前的研究表明， NG 2细胞（也称为少突胶质细胞前体细胞，或OPC），一类祖细胞发现， 普遍存在于灰质和白色物质中，表达谷氨酸和GABA的功能性离子型受体 这表明传统的神经递质可能在细胞信号传导中具有广泛的作用。这些 NG 2细胞中的低亲和力受体通过神经元的递质的量子释放而被激活， 导致NG 2细胞膜的瞬时去极化。突触信号的存在 神经元和NG 2细胞在海马体中的作用提出了许多新的问题， 在调节这些神秘细胞的特性和发育方面，我们假设 神经元-NG 2细胞突触信号传导是一种普遍存在的调节细胞增殖的机制， NG 2细胞在大脑中的发育。转基因小鼠的可用性，其中荧光蛋白 DsRed在所有NG 2细胞中的表达为我们研究其相互作用提供了前所未有的机会 神经元和NG 2细胞之间的关系。我们建议使用单细胞 电生理学方法，高分辨率电子显微镜，和转基因操作， NG 2细胞中的谷氨酸受体，以确定NG 2细胞表达的受体的性质， 大脑区域，负责激活这些受体的机制，以及这种信号在 调节NG 2细胞行为。这些研究将评估特定的假设，即Ca 2+通过 这些AMPA受体在调节NG 2细胞的增殖和分化中起中心作用。 由于这些细胞作为少突胶质细胞祖细胞，并具有多能性， 了解原位调节NG 2细胞行为的因素可能会导致新的策略， 预防早产儿的髓鞘损伤，并替换受损的神经元和神经胶质， 缺血或因疾病而丢失。

Glial cells in the mammalian CMS are responsible for creating and maintaining an environment where neuronal activity can be sustained, and are capable of modulating this activity. This close interrelationship between neurons and non-neuronal cells suggests that mechanisms may exist to rapidly adjust glial cell behavior in response to changes in the needs of surrounding neurons. Our previous studies indicate that NG2 cells (also known as oligodendrocyte precursor cells, or OPCs), a class of progenitor cells found ubiquitously in both gray and white matter, express functional ionotropic receptors for glutamate and GABA in situ, suggesting that conventional neurotransmitters may have widespread roles in cell signaling. These low affinity receptors are activated in NG2 cells by the quantal release of transmitter from neurons, which result in transient depolarizations of the NG2 cell membrane. The existence of synaptic signaling between neurons and NG2 cells in the hippocampus raises many new questions about the role of this rapid communication in regulating the properties and development of these enigmatic cells. We hypothesize that neuron-NG2 cell synaptic signaling is a ubiquitous mechanism for regulating the proliferation and development of NG2 cells in the brain. The availability of transgenic mice in which the fluorescent protein DsRed is expressed in all NG2 cells provides us with an unprecedented opportunity to study the interaction between neurons and NG2 cells within intact slices of mammalian brain. We propose to use single cell electrophysiological methods, high resolution electron microscopy, and transgenic manipulation of glutamate receptors in NG2 cells, to define the properties of receptors expressed by NG2 cells in different brain regions, the mechanisms responsible for activation of these receptors, and the role of this signaling in regulating NG2 cell behavior. These studies will evaluate the specific hypothesis that Ca2+ influx through these AMPA receptors plays a central role in regulating the proliferation and differentiation NG2 cells. Because these cells serve as oligodendrocyte progenitors and have multipotent capability, a better understanding of the factors that regulate the NG2 cells behavior in situ may lead to new strategies for preventing myelin damage in pre-term infants, and replacing neurons and glia that have been injured as a result of ischemia or lost through disease.