Panglial calcium signalling in the olfactory bulb

在过去的二十年里，越来越明显的是，神经胶质细胞是神经系统中对大脑功能起作用的重要和活跃的组成部分。很少有研究表明，不同类型的胶质细胞，如星形胶质细胞和少突胶质细胞，通过缝隙连接相互连接，形成所谓的苍白球网络。Panglial网络被认为支持K+的虹吸和轴突的代谢供应，然而，钙信号是否通过Panglial途径从一种类型的神经胶质细胞传递到另一种类型的神经胶质细胞之前并未得到证实。这项拟议的项目旨在证明，在小鼠中，星形胶质细胞中诱发的钙瞬变可以传递给嗅鞘胶质细胞(OECs)，OECs是一种特殊类型的胶质细胞，具有星形胶质细胞和少突胶质细胞的特性。嗅鞘细胞位于嗅球的浅层，也就是神经层，在那里它们包裹着一束束轴突，并与位于嗅球深层的星形胶质细胞胞体很好地分开。然而，星形胶质细胞将一些突起投射到神经层，这表明星形胶质细胞和嗅鞘细胞之间可能存在相互作用。我们的初步结果表明，星形胶质细胞和嗅鞘细胞是通过连接蛋白43形成的缝隙连接连接起来的。拟议的实验将检验这样一种假设，即星形胶质细胞局部诱发的钙瞬变，例如通过激光介导的代谢性谷氨酸受体激动剂AcPD的光激活，可以通过缝隙连接传递到嗅鞘细胞，从而建立苍白球钙信号。Panglial钙信号随后在被嗅鞘细胞包裹的血管中触发血管反应。该项目将有助于我们了解神经胶质细胞如何相互通信，以及这如何解释大脑功能的调节和维持。

During the past two decade, it has become more and more obvious that glial cells are essential and active components of the nervous system contributing to brain function. Few studies have shown that different types of glial cells such as astrocytes and oligodendrocytes are coupled by gap junctions to each other to form so-called panglial networks. Panglial networks are supposed to support K+ siphoning and metabolic supply of axons, however, whether calcium signalling is transmitted from one type of glial cell to another via panglial routes has not been shown before. The proposed project aims to show that in mice calcium transients evoked in astrocytes can be transmitted to olfactory ensheathing glial cells (OECs), a specialized type of glial cells that share properties of both astrocytes and oligodendrocytes. OECs are found in the superficial layer of the olfactory bulb, the nerve layer, where they ensheath bundles of axons and are well seperated from astrocyte cell bodies which are located in deeper layers of the olfactory bulb. However, astrocytes project some proccesses into the nerve layer, suggesting possible interactions between astrocytes and OECs. Our preliminary results indicate that astrocytes and OECs are coupled by gap junctions formed by connexin 43. The proposed experiments will test the hypothesis that calcium transients locally evoked in astrocytes, e.g. by laser-mediated photoactivation of the "caged" agonist of metabotropic glutamate receptors, ACPD, can be transmitted to OECs via gap junctions and thereby establish panglial calcium signalling. Panglial calcium signalling subsequently triggers vasoresponses in blood vessels enwrapped by OECs. The project will contribute to our understanding how glial cells communicate with each other and how this accounts for regulation and maintenance of brain function.