Gliotransmitter release in astrocytic heterogeneity and brain activity

本项目探讨星形胶质细胞-神经元通讯在协调突触传递中的重要作用。在持续的资助期内，我们已经提供了强有力的证据，证明星形胶质细胞中存在独立的分泌途径，这些分泌途径使用SynaptobrevinII （SybII）和Cellubrevin （Ceb）作为功能上不重叠的v-SNARE蛋白，并相反地调节快速谷氨酸能神经传递。因此，我们可以阐明星形胶质细胞信号通路的异质性和多样性，这可能是神经元-星形胶质细胞双向通信的一个组成部分，为进一步实验描述胶质传递如何在体内塑造神经元信号奠定了基础。通过结合高分辨率成像和多种v-SNARE缺失突变体（构成型和细胞类型特异性敲除）以及不同Synaptotagmin缺陷小鼠的电生理记录，我们将研究不同胶质递质分泌途径的激活，它们对星形胶质细胞功能异质性的贡献以及在大脑疾病背景下的参与。

This project investigates the important role of astrocyte-neuron communication in orchestrating synaptic transmission. In the ongoing funding period, we have provided strong evidence for the co-existence of independent secretion pathways in astrocytes that employ SynaptobrevinII (SybII) and Cellubrevin (Ceb) as functionally non-overlapping v-SNARE proteins and oppositely regulate fast glutamatergic neurotransmission. Thereby, we could elucidate the heterogeneity and diversity of astrocytic signaling pathways, which may represent an integral part of bidirectional neuron-astrocyte communication, setting the stage for further experiments to delineate how gliotransmission shapes neuronal signaling in vivo. By using electrophysiological recordings in combination with high-resolution imaging and a variety of v-SNARE null mutants (constitutive and cell-type specific knock outs) as well as different Synaptotagmin deficient mice, we will investigate the activation of distinct gliotransmitter secretion pathways, their contribution to the heterogeneity of astrocyte function and participation in the context of cerebral disorders.