Glial responses at neuronal synapses and their purinergic modulation

我们对胶质细胞的重要性，特别是关于它在大脑中的信息处理作用的了解仍然相当有限。这种信息处理的主要位置之一是神经元之间的化学突触。鉴于新的发现，神经胶质细胞，特别是星形胶质细胞，必须作为第三个整合伙伴被包括在突触过程中。到目前为止，星形胶质细胞的数量远远超过哺乳动物大脑中的神经元，它们经常通过小的突触周围突触来接近突触区域。浦肯野神经元(PN)和Bergmann胶质细胞(BG)在小脑内的紧密联系，为研究突触区域的神经节相互作用提供了有利的准备。每个PN接受大量的突触输入，周围环绕着几个BG，这些BG的过程投射到PN的广泛树状树状结构中，吞噬突触微域。我们已经证明，电刺激单个BG细胞减少了邻近PN中突触事件的频率。这种调节是通过激活离子型、非NMDA型、谷氨酸能和嘌呤能P2受体来实现的。在这个项目中，我们想要阐明刺激BG启动的过程，以及BG细胞调节突触输入到PN的机制。本研究的目的是确定BG细胞是否直接或间接地参与调节分子层的回路活动，从而调节小脑皮质的信息处理。

Our knowledge about the significance of glia, in particular with respect to its role for information processing in the brain, is still rather limited. One of the prime locations of this information processing are chemical synapses between neurons. In view of new findings, glial cells, and astrocytes in particular, must be included in the synaptic process as a third, integrative partner. Astrocytes, which by far outnumber neurons in the mammalian brain, often approach synaptic domains with their small perisynaptic processes. The close association of Purkinje neurons (PN) and Bergmann glia (BG) in the cerebellum, offers a favourable preparation to study neuronglia interactions at synaptic domains. Each PN, which receives a vast number of synaptic inputs, is surrounded by several BGs, whose processes project into the extensive dendritic tree of the PN and engulf synptic microdomains. We have shown that electrical stimulation of single BG cells reduces the frequency of synaptic events in the neighbouring PN. This modulation is mediated by the activation of ionotropic, non-NMDA, glutamatergic and of purinergic P2 receptors. In this project we want to elucidate the processes initiated by BG stimulation, and the mechanisms by which BG cells modulate the synaptic input to PN. It is the aim of the present study to establish, whether BG cells are directly or indirectly involved in modulating the circuit activity of the molecular layer, and thus the information processing of the cerebellar cortex.