The specific role of BDNF-triggered synaptic activation in synapse development of hippocampal neurons

BDNF触发的突触激活在海马神经元突触发育中的具体作用

• 批准号: 167773420
• 负责人: Dr. Kristin Michaelsen-Preusse
• 金额: --
• 依托单位: Zoologisches Institut
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/167773420?language=en
• 关键词: specific; role; BDNF; triggered; synaptic

The establishment of neuronal networks during development requires the precise formation of synaptic connections. Despite the increasing wealth of data concerning the question of how neuronal networks are wired with high precision the underlying mechanisms still remain elusive. This project is aimed at investigating the precise role of BDNF-triggered activation of individual developing synapses in hippocampal slice cultures. Interestingly, the focal application of BDNF to immature silent synapses leads to a very high frequency of spontaneous transmission events for a period of at least one hour after BDNF application. To investigate the role of BDNF during early synapse development, the new mechanism of BDNF-triggered unsilencing of individual synapses will be identified. It will be also interesting to investigate the minimal stimulation intensity, the duration of activation, and what types of synapses can be activated. In addition, I will ask the question if the mechanism of synapse activation is pre- or postsynaptically. As a second step, I will address whether the unsilencing of individual synapses is specific to the application of BDNF or whether it could occur as well by transactivation of TrkB receptors. As BDNF levels might be limited in the developing hippocampus it is still a matter of particular interest if TrkB signaling independent of neurotrophins could as well be crucial during early synaptogenesis.

发育过程中神经元网络的建立需要突触连接的精确形成。尽管关于神经元网络如何高精度连接的问题的数据越来越丰富，但潜在的机制仍然难以捉摸。该项目旨在研究海马切片培养物中 BDNF 触发的个体发育突触激活的精确作用。有趣的是，将 BDNF 集中应用于未成熟的沉默突触会导致在 BDNF 应用后至少一小时内发生非常高频率的自发传播事件。为了研究 BDNF 在早期突触发育过程中的作用，将确定 BDNF 触发个体突触非沉默的新机制。研究最小刺激强度、激活持续时间以及可以激活什么类型的突触也很有趣。另外，我会问突触激活机制是突触前还是突触后的问题。第二步，我将讨论单个突触的非沉默是否特定于 BDNF 的应用，或者是否也可以通过 TrkB 受体的反式激活来发生。由于 BDNF 水平在发育中的海马体中可能受到限制，因此独立于神经营养因子的 TrkB 信号传导在早期突触发生过程中是否也至关重要，这仍然是一个特别令人感兴趣的问题。