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Astrocyte-to-neuron communication: functional relevance for synaptic transmission in the respiratory network?

星形胶质细胞到神经元的通讯：呼吸网络中突触传递的功能相关性？

基本信息

批准号：
82921243
负责人：
Professor Dr. Swen Hülsmann
金额：
--
依托单位：
Klinik für Anästhesiologie
依托单位国家：
德国
项目类别：
Priority Programmes
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2010-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/82921243?language=en
关键词：
Astrocyte neuron communication functional relevance

项目摘要

Astrocytes have now been identified as key players for normal brain function. Presumably most important is their contribution to the stabilization of the environment of neurons, due to their capability to regulate the extracellular concentration of potassium as well as neurotransmitters. Moreover, it has become evident that astrocytes themselves can utilize and release transmitter (so called gliotransmitters) to signal to neurons. This kind of astrocyte-to-neuron communication has been shown to depend on a calcium-dependent release of e.g. glutamate or ATP from astrocytes, thus, astrocyte are capable to influence synaptic transmission directly. In the respiratory centre, however our understanding of the role of astrocyte-derived transmitter molecules for synapses between respiratory neurons is still rudimentary. In the proposed project we shall answer the following questions regarding astrocyte-to-neuron communication in the ventral respiratory group (VRG) of the caudal medulla: Do astrocytes in the VRG release gliotransmitters to neighboring respiratory neurons and synapses? Do spontaneous astrocytic calcium oscillations trigger gliotransmitter release in VRG astrocytes? Which conditions are required to influence the entire network? To answer these questions we will combine electrophysiological and optical techniques. We will perform dual whole-cell recordings from pairs of identified astrocytes and neighboring respiratory neurons. This allows on the one side a direct manipulation of the astrocyte using electrical stimulation, un-caging of second messengers or intracellular perfusion of specific antagonists and on the other to monitor synaptic transmission by recording inhibitory or excitatory postsynaptic currents. In parallel we will image and modulate astrocytic calcium signals during ongoing respiratory network activity.

星形胶质细胞现已被确定为正常大脑功能的关键参与者。据推测，最重要的是它们对稳定神经元环境的贡献，因为它们具有调节细胞外钾浓度和神经递质的能力。此外，很明显，星形胶质细胞本身可以利用和释放递质（所谓的神经胶质递质）向神经元发出信号。这种星形胶质细胞与神经元的通讯已被证明依赖于钙依赖性释放，例如来自星形胶质细胞的谷氨酸或ATP，因此，星形胶质细胞能够直接影响突触传递。然而，在呼吸中枢，我们对星形胶质细胞衍生的递质分子在呼吸神经元之间突触中的作用的理解仍然很初级。在拟议的项目中，我们将回答以下有关尾髓腹侧呼吸群（VRG）中星形胶质细胞与神经元通讯的问题：VRG中的星形胶质细胞是否向邻近的呼吸神经元和突触释放胶质递质？自发性星形胶质细胞钙振荡是否会触发 VRG 星形胶质细胞释放胶质递质？影响整个网络需要哪些条件？为了回答这些问题，我们将结合电生理学和光学技术。我们将对已识别的星形胶质细胞和邻近的呼吸神经元对进行双全细胞记录。这一方面允许使用电刺激、第二信使的解禁或特定拮抗剂的细胞内灌注来直接操纵星形胶质细胞，另一方面允许通过记录抑制性或兴奋性突触后电流来监测突触传递。与此同时，我们将在持续的呼吸网络活动期间成像和调节星形胶质细胞钙信号。