Role of BDNF signaling for striatal plasticity and motor learning (A05)

本项目旨在研究黑质多巴胺能活动和丘脑底核深部脑刺激(DBS)如何调节皮质纹状体传入的脑源性神经营养因子(BDNF)的释放和纹状体中棘神经元的原肌球蛋白受体激酶B(TrkB)反应性。该项目以我们在细胞培养技术方面的专业知识为基础，用于丰富中等刺神经元和新的肌张力障碍小鼠模型，以及这些皮质纹状体突触中的BDNF信号受到干扰的模型。我们的目标是了解该突触的可塑性机制如何导致帕金森病患者S病和肌张力障碍的运动缺陷，以及STN的DBS如何调节该突触和运动功能。

This project is designed to investigate how the release of brain-derived neurotrophic factor (BDNF) from corticostriatal afferents and tropomyosin receptor kinase B (TrkB) responsiveness in striatal medium spiny neurons are regulated by dopaminergic activity from the substantia nigra and by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The project builds on our expertise with cell culture techniques for enrichment of medium spiny neurons and new mouse models of dystonia, as well as models in which BDNF signaling in these corticostriatal synapses is disturbed. The goal is to understand how plasticity mechanisms at this synapse contribute to motor defects in Parkinson´s disease and dystonia, and how DBS of the STN modulates this synapse and motor function.