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

在发育过程中建立神经元网络需要精确地形成突触连接。尽管关于神经元网络如何以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。该项目旨在研究脑源性神经营养因子在海马片培养中激活个体发育中的突触的确切作用。有趣的是，将BDNF集中应用于未成熟的沉默突触会导致在应用BDNF后至少一小时内发生非常高频率的自发传递事件。为了研究BDNF在突触早期发育中的作用，我们将确定BDNF触发单个突触去沉默的新机制。研究最小刺激强度、激活持续时间以及可以激活哪些类型的突触也将是有趣的。此外，我会问一个问题，突触激活的机制是突触前还是突触后。作为第二步，我将讨论单个突触的解除沉默是否专用于BDNF的应用，或者它是否也可以通过TrkB受体的反式激活而发生。由于BDNF在发育中的海马区的水平可能有限，因此TrkB信号是否独立于神经营养因子在早期突触发生中也是至关重要的，这仍然是一个特别令人感兴趣的问题。

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.