Glial responses at neuronal synapses and their purinergic modulation

我们对神经胶质的重要性的认识，特别是它在大脑信息处理中的作用，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，胶质细胞，特别是星形胶质细胞，必须包括在突触过程中作为第三个，整合的伙伴。在哺乳动物的大脑中，星形胶质细胞的数量远远超过神经元，它们经常通过小的突触周围过程接近突触域。浦肯野神经元（PN）和伯格曼胶质细胞（BG）在小脑中的密切联系，为研究神经胶质在突触域的相互作用提供了有利的准备。每个PN接收大量突触输入，被几个bg包围，其过程投射到PN的广泛树突树并吞噬突触微域。我们已经证明，对单个BG细胞的电刺激会降低邻近PN中突触事件的频率。这种调节是由嗜离子性、非nmda、谷氨酸能和嘌呤能P2受体的激活介导的。在这个项目中，我们想要阐明由BG刺激启动的过程，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参与调节分子层的电路活动，从而参与小脑皮层的信息处理。

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.