PDF(Pubmed)
Abstract：
Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between the principal neuron in the medial nucleus of the trapezoid body (MNTB) and the principal neuron in the lateral superior olive (LSO) in the auditory brainstem. Combining RNAscope with stereotactic injection of AAV-Cre in the MNTB of neurexin1/2/3 conditional triple knockout mice, we showed that MNTB neurons highly express all isoforms of neurexins although their expression levels vary remarkably. Selective ablation of all neurexins in MNTB neurons not only reduced the amplitude but also altered the kinetics of the glycinergic synaptic transmission at LSO neurons. The synaptic dysfunctions primarily resulted from an impaired Ca2+ sensitivity of release and a loosened coupling between voltage-gated Ca2+ channels and synaptic vesicles. Together, our current findings demonstrate that neurexins are essential in controlling the strength and temporal precision of the glycinergic synapse, which therefore corroborates the role of neurexins as key presynaptic organizers in all major types of fast chemical synapses.
摘要：
Neurexins在各种谷氨酸能和GABA能突触中起着突触前组织者的多种功能。然而,目前尚不清楚神经素是否以及如何参与形成甘氨酸能突触的功能特性，介导脑干和脊髓的显著抑制。为了解决这些问题,我们研究了神经素在梯形体内侧核（MNTB）的主要神经元和听觉脑干外侧上橄榄（LSO）的主要神经元之间的模型甘氨酸能突触中的作用。在Neurexin1/2/3条件三重基因敲除小鼠的MNTB中结合RNAscope和立体定向注射AAV-Cre，我们表明，尽管MNTB神经元的表达水平差异很大，但它们的所有亚型均高度表达。MNTB神经元中所有神经素的选择性消融不仅降低了幅度，而且改变了LSO神经元上甘氨酸能突触传递的动力学。突触功能障碍主要是由于释放的Ca2敏感性受损以及电压门控的Ca2通道与突触小泡之间的耦合松动所致。一起,我们目前的研究结果表明，神经素对于控制甘氨酸能突触的强度和时间精度至关重要，因此，这证实了神经素在所有主要类型的快速化学突触中作为关键突触前组织者的作用。
