Abstract

Sydney Brenner’s choice of Caenorhabditis elegans as a model organism for understanding the nervous system has accelerated discoveries of gene function in neural circuit development and behavior. In this review, we discuss a striking example of synaptic remodeling in the C. elegans motor circuit in which DD class motor neurons effectively reverse polarity as presynaptic and postsynaptic domains at opposite ends of the DD neurite switch locations. Originally revealed by EM reconstruction conducted over 40 years ago, DD remodeling has since been investigated by live cell imaging methods that exploit the power of C. elegans genetics to reveal key effectors of synaptic plasticity. Although synapses are also extensively rewired in developing mammalian circuits, the underlying remodeling mechanisms are largely unknown. Here, we highlight the possibility that studies in C. elegans can reveal pathways that orchestrate synaptic remodeling in more complex organisms. Specifically, we describe (1) transcription factors that regulate DD remodeling, (2) the cellular and molecular cascades that drive synaptic remodeling and (3) examples of circuit modifications in vertebrate neurons that share some similarities with synaptic remodeling in C. elegans DD neurons.

 抽象的

西德尼·布伦纳 (Sydney Brenner) 选择秀丽隐杆线虫作为了解神经系统的模式生物，加速了神经回路发育和行为中基因功能的发现。在这篇综述中，我们讨论了秀丽隐杆线虫运动回路中突触重塑的一个引人注目的例子，其中 DD 类运动神经元有效地反转极性，作为 DD 神经突开关位置两端的突触前和突触后域。 DD 重塑最初由 40 多年前进行的 EM 重建揭示，此后通过活细胞成像方法进行研究，利用线虫遗传学的力量来揭示突触可塑性的关键效应器。尽管突触在发育中的哺乳动物回路中也被广泛地重新连接，但潜在的重塑机制在很大程度上是未知的。在这里，我们强调了对秀丽隐杆线虫的研究可以揭示在更复杂的生物体中协调突触重塑的途径的可能性。具体来说，我们描述了（1）调节 DD 重塑的转录因子，（2）驱动突触重塑的细胞和分子级联，以及（3）脊椎动物神经元中电路修饰的示例，这些修饰与秀丽隐杆线虫DD 神经元中的突触重塑有一些相似之处。