Department of Neurobiology and Behavior, University of California Irvine, Irvine, California 92697, USA.
J Comp Neurol. 2010 Apr 1;518(7):972-89. doi: 10.1002/cne.22258.
Synaptogenesis is a dynamic process that involves structural changes in developing axons and dendrites as synapses form and mature. The visual system of Xenopus laevis has been used as a model to study dynamic changes in axons and dendrites as synapses form in the living brain and the molecular mechanisms that control these processes. Brain-derived neurotrophic factor (BDNF) contributes to the establishment and refinement of visual connectivity by modulating retinal ganglion cell (RGC) axon arborization and presynaptic differentiation. Here, we have analyzed the ultrastructural organization of the Xenopus retinotectal system to understand better the maturation of this synaptic circuit and the relation between synapse ultrastructure and the structural changes in connectivity that take place in response to BDNF. Expression of yellow fluorescent protein (YFP) followed by preembedding immunoelectron microscopy was used to identify RGC axons specifically in living tadpoles. Injection of recombinant BDNF was used to alter endogenous BDNF levels acutely in the optic tectum. Our studies reveal a rapid transition from a relatively immature synaptic circuit in which retinotectal synapses are formed on developing filopodial-like processes to a circuit in which RGC axon terminals establish synapses with dendritic shafts and spines. Moreover, our studies reveal that BDNF treatment increases the number of spine synapses and docked vesicle number at YFP-identified synaptic sites within 24 hours of treatment. These fine structural changes at retinotectal synapses are consistent with the role that BDNF plays in the functional maturation of synaptic circuits and with dynamic, rapid changes in synaptic connectivity during development.
突触发生是一个动态的过程，涉及到形成和成熟的突触的发育轴突和树突的结构变化。非洲爪蟾的视觉系统已被用作模型来研究活体大脑中形成突触时轴突和树突的动态变化，以及控制这些过程的分子机制。脑源性神经营养因子（BDNF）通过调节视网膜神经节细胞（RGC）轴突分支和突触前分化，有助于视觉连接的建立和完善。在这里，我们分析了非洲爪蟾的视网膜-顶盖系统的超微结构组织，以更好地了解这个突触回路的成熟，以及突触超微结构与BDNF 作用下发生的连接结构变化之间的关系。表达黄色荧光蛋白（YFP），然后进行预包埋免疫电镜，用于在活体蝌蚪中特异性识别 RGC 轴突。注射重组 BDNF 用于急性改变视顶盖中的内源性 BDNF 水平。我们的研究揭示了一个快速的转变，即从相对不成熟的突触回路，其中视网膜-顶盖突触形成在发育中的丝状突起上，到 RGC 轴突末端与树突干和棘突建立突触的回路。此外，我们的研究表明，BDNF 处理在 24 小时的处理时间内增加了 YFP 鉴定的突触部位的棘突突触和停泊囊泡数量。这些视网膜-顶盖突触的精细结构变化与 BDNF 在突触回路的功能成熟中的作用以及发育过程中突触连接的动态快速变化一致。
