脑功能是由特定的神经元回路执行。回路的构建依赖于不同的神经元形成特异的化学突触以实现多样化可变的信息处理。架构复杂有序的突触前和突触后结构以及它们的精确铆合对正常的突触形成和功能都很重要。Neurexins是重要的突触前细胞粘附分子，其基因突变与各种神经精神疾病密切关联。有力证据表明neurexins在突触建立及突触传递过程中都有着许多关键作用。然而，neurexins在调节突触前活动区功能组织中的确切作用仍然未知。利用Calyx of Held（CH）突触作为系统模型，并结合PV-Cre/neurexin1-2-3三重条件性基因敲除小鼠，我们的预实验结果表明neurexins的缺失不影响CH突触的形成，其功能却被显著削弱，而突触前钙电流并无变化。我们拟系统分析neurexins如何多方面参与突触前活动区的功能调控。该研究将加深我们理解neurexins如何调控突触形成及功能。

All brain functions are executed by distinct neural circuits, which are built upon the formation of unique chemical synapses between neurons in order to achieve diverse and dynamic information processing. Assembling highly-organized presynaptic and postsynaptic apparatus and their precise alignment are essential for synapse formation and function. Neurexins are key presynaptic cell adhesion molecules whose mutations are tightly associated with various neuropsychiatric diseases. Accumulating evidence has shown that neurexins play important roles in the proper formation and function of synapses. However, it remains largely unclear what are their exact roles particularly in controlling presynaptic active zone functional organization. Taking advantage of the calyx of Held (CH) synapse as a model system, in combination with the invaluable PV-Cre/neurexin1-2-3 triple conditional knockout mice, our preliminary results have revealed that pan-neurexins deletion did not affect the initial synapse formation but severely impaired the synaptic function, which was not caused by reduction in presynaptic Ca2+ current. We propose to investigate systematically the exact roles of neurexins in organizing presynaptic active zones and explore the underlying molecular and cellular mechanisms. The study will deepen our understanding of the roles of neurexins in regulating synapse formation and function.