Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom.
Department of Anatomy, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
Cereb Cortex. 2021 Mar 31;31(5):2625-2638. doi: 10.1093/cercor/bhaa379.
Synapses are able to form in the absence of neuronal activity, but how is their subsequent maturation affected in the absence of regulated vesicular release? We explored this question using 3D electron microscopy and immunoelectron microscopy analyses in the large, complex synapses formed between cortical sensory efferent axons and dendrites in the posterior thalamic nucleus. Using a Synaptosome-associated protein 25 conditional knockout (Snap25 cKO), we found that during the first 2 postnatal weeks the axonal boutons emerge and increase in the size similar to the control animals. However, by P18, when an adult-like architecture should normally be established, axons were significantly smaller with 3D reconstructions, showing that each Snap25 cKO bouton only forms a single synapse with the connecting dendritic shaft. No excrescences from the dendrites were formed, and none of the normally large glomerular axon endings were seen. These results show that activity mediated through regulated vesicular release from the presynaptic terminal is not necessary for the formation of synapses, but it is required for the maturation of the specialized synaptic structures between layer 5 corticothalamic projections in the posterior thalamic nucleus.
突触可以在没有神经元活动的情况下形成，但在没有调节性囊泡释放的情况下，它们随后的成熟会受到怎样的影响？我们使用 3D 电子显微镜和免疫电子显微镜分析，研究了这个问题，分析对象是大脑皮层感觉传出轴突和丘脑后核树突之间形成的大型复杂突触。我们利用突触相关蛋白 25 条件性敲除（Snap25 cKO）模型，发现突触前末梢的囊泡释放活动对突触的形成并不必需，在出生后的前 2 周，突触前轴突末梢会出现并增大，与对照组动物相似。然而，到 P18 时，正常情况下应该建立起成熟的形态结构，但 Snap25 cKO 轴突明显更小，3D 重建显示每个 Snap25 cKO 末梢只与连接的树突干形成一个单一的突触。树突上没有形成突起，也没有看到正常的大球型轴突终末。这些结果表明，通过突触前末梢的调节性囊泡释放来介导的活动对于形成突触并不是必需的，但对于丘脑后核中第 5 层皮质丘脑投射之间的特殊突触结构的成熟是必需的。
