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种环境， 神经元的活动是可以持续的，并且能够调节这种活动。这种密切的相互关系 神经元和非神经元细胞之间的关系表明可能存在快速调节神经胶质细胞的机制 对周围神经元需求变化做出反应的行为。我们之前的研究表明， NG2细胞(也称为少突胶质前体细胞，简称OPC)，是一类被发现的祖细胞 在灰质和白质中普遍存在，表达谷氨酸和GABA的功能性离子亲电受体 这表明传统的神经递质可能在细胞信号转导中具有广泛的作用。这些 NG2细胞中的低亲和力受体是通过神经元递质的量子释放而激活的，这是 导致NG2细胞膜的瞬时去极化。突触信号的存在 海马神经元和NG2细胞对这种快速反应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的交流。我们假设 神经元-NG2细胞突触信号是一种普遍存在的调节细胞增殖和 大脑中NG2细胞的发育。转基因小鼠中荧光蛋白的可用性 DsRed在所有NG2细胞中都有表达，这为我们提供了一个前所未有的研究相互作用的机会 在哺乳动物大脑完整切片内的神经元和NG2细胞之间。我们建议使用单电池 电生理学方法、高分辨率电子显微镜和转基因操作 谷氨酸受体在NG2细胞中的表达，以明确NG2细胞在不同时期表达的受体的特性 大脑区域，负责激活这些受体的机制，以及这种信号在 调节NG2细胞的行为。这些研究将评估钙离子通过 这些AMPA受体在调节NG2细胞的增殖和分化中起着中心作用。 由于这些细胞作为少突胶质前体细胞并具有多潜能，因此更好地 了解在原位调节NG2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，并取代作为一种 缺血或通过疾病丢失的结果。

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.