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

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以高精度连接的问题的数据越来越丰富，但其潜在机制仍然难以捉摸。该项目旨在研究海马切片培养中bdnf触发的个体发育突触激活的确切作用。有趣的是，将BDNF集中应用于未成熟的沉默突触会导致在BDNF应用后至少一小时内自发传递事件的频率非常高。为了研究BDNF在早期突触发育中的作用，将确定BDNF触发单个突触解除沉默的新机制。研究最小的刺激强度，激活的持续时间，以及什么类型的突触可以被激活，也将是很有趣的。此外，我将提出突触激活的机制是突触前还是突触后的问题。作为第二步，我将讨论单个突触的解除沉默是否特定于BDNF的应用，或者是否也可能通过TrkB受体的反激活发生。由于BDNF水平在发育中的海马体中可能受到限制，因此，是否独立于神经营养因子的TrkB信号在早期突触发生中也起着至关重要的作用，仍然是一个特别有趣的问题。

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.