Specificity of synapse formation in Aplysia: paracrine and autocrine signaling regulates bidirectional molecular interactions between sensory and non-target motor neurons.
Specificity of synapse formation in Aplysia: paracrine and autocrine signaling regulates bidirectional molecular interactions between sensory and non-target motor neurons.
复制标题
海兔突触形成的特异性：旁分泌和自分泌信号调节感觉和非目标运动神经元之间的双向分子相互作用。
DOI：
10.1038/s41598-020-62099-4
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发表时间：
2020
影响因子：
4.6
通讯作者：
Carew,ThomasJames
中科院分区：
文献类型：
--
作者：
Alexandrescu,Anamaria;Carew,ThomasJames
在发育过程中形成适当的神经连接对于大脑的正常布线和功能至关重要。虽然相当多的研究表明，突触形成的特异性是由潜在的突触前和突触后伙伴之间的复杂的细胞间信号传导支持的，但参与这一过程的细胞外因子和细胞内信号转导通路在很大程度上仍然未知。使用的感觉运动神经回路，有助于学习防御性退缩反射inAussiacalifornica，我们调查的分子过程中的突触形成过程中的感觉神经元和目标和非目标运动神经元之间的相互作用的文化。我们发现，进化上保守的细胞间和细胞内的信号传导机制，学习相关的可塑性的关键也参与了突触发生在这个体外模型系统。我们的研究结果揭示了一个令人惊讶的双向调节感觉神经元和非目标运动神经元之间的分子信号。这种调节是通过旁分泌和自分泌扩散因子的信号传导介导的，所述旁分泌和自分泌扩散因子诱导对感觉神经元以及靶和非靶运动神经元中的转录和蛋白质表达/活化的差异效应。总的来说，我们的数据揭示了新的分子机制，可能是抑制不适当的突触形成的基础，并表明发育和学习相关的可塑性之间的机制相似性。
The formation of appropriate neural connections during development is critical for the proper wiring and functioning of the brain. Although considerable research suggests that the specificity of synapse formation is supported by complex intercellular signaling between potential presynaptic and postsynaptic partners, the extracellular factors and the intracellular signal transduction pathways engaged in this process remain largely unknown. Using the sensory-motor neural circuit that contributes to learning in defensive withdrawal reflexes inAplysia californica, we investigated the molecular processes governing the interactions between sensory neurons and both target and non-target motor neurons during synapse formation in culture. We found that evolutionarily-conserved intercellular and intracellular signaling mechanisms critical for learning-related plasticity are also engaged during synaptogenesis in thisin vitromodel system. Our results reveal a surprising bidirectional regulation of molecular signaling between sensory neurons and non-target motor neurons. This regulation is mediated by signaling via both paracrine and autocrine diffusible factors that induce differential effects on transcription and on protein expression/activation in sensory neurons and in target and non-target motor neurons. Collectively, our data reveal novel molecular mechanisms that could underlie the repression of inappropriate synapse formation, and suggest mechanistic similarities between developmental and learning-related plasticity.