2025年11月19日出版的《自然》杂志发表了斯坦福大学骆利群研究组的最新成果，他们探明了通过改变细胞表面的组合代码来重新连接嗅觉回路。

在这里，该课题组人员以果蝇嗅觉回路中的突触伴侣匹配为主题来解决这个问题。通过系统地改变一种嗅觉受体神经元（ORN）中差异表达的CSPs的组合，小组将其连接几乎完全从内源性突触后投射神经元（PN）类型转换为一种新的PN类型，促进它们之间的联系。从这个开关中，该研究组推导出一个组合代码，包括CSPs，它既介导突触伙伴之间的吸引，也介导非伙伴之间的排斥。解剖开关改变了新的PN伴侣的反应，显著增加了雄性与雄性之间的关系。该课题组从这种重新布线中归纳出三种操作策略-增加与旧伙伴的排斥力，减少与新伙伴的排斥力以及与新伙伴匹配的吸引力-成功地将第二种ORN类型重新连接到多个不同的PN类型。这项工作表明，操纵一小组CSPs足以重新指定突触连接，为研究神经系统如何通过电路连接的变化而进化铺平了道路。

据介绍，正常的大脑功能需要发育过程中神经回路的精确组装。尽管已经鉴定出许多细胞表面蛋白（CSPs）可以帮助引导轴突到达它们的靶标，但仍不清楚多个CSPs如何协同工作以组装一个功能电路。

附：英文原文

Title: Rewiring an olfactory circuit by altering cell-surface combinatorial code

Author: Lyu, Cheng, Li, Zhuoran, Xu, Chuanyun, Kalai, Jordan, Luo, Liqun

Issue&Volume: 2025-11-19

Abstract: Proper brain function requires the precise assembly of neural circuits during development. Despite the identification of many cell-surface proteins (CSPs) that help guide axons to their targets1,2, it remains mostly unknown how multiple CSPs work together to assemble a functional circuit. Here we used synaptic partner matching in the Drosophila olfactory circuit3,4 to address this question. By systematically altering the combination of differentially expressed CSPs in a single type of olfactory receptor neuron (ORN), which senses a male pheromone that inhibits male–male courtship, we switched its connection nearly completely from its endogenous postsynaptic projection neuron (PN) type to a new PN type that promotes courtship. From this switch, we deduced a combinatorial code including CSPs that mediate both attraction between synaptic partners and repulsion between non-partners5,6. The anatomical switch changed the odour response of the new PN partner and markedly increased male–male courtship. We generalized three manipulation strategies from this rewiring—increasing repulsion with the old partner, decreasing repulsion with the new partner and matching attraction with the new partner—to successfully rewire a second ORN type to multiple distinct PN types. This work shows that manipulating a small set of CSPs is sufficient to respecify synaptic connections, paving the way to investigations of how neural systems evolve through changes of circuit connectivity.

DOI: 10.1038/s41586-025-09769-3

Source: https://www.nature.com/articles/s41586-025-09769-3