美国杜克大学Kafui Dzirasa团队的最新研究提出了利用工程电突触对大脑回路进行长期编辑。2026年5月13日出版的《自然》发表了这项成果。

在这里，课题组研究人员设计了一个由两种连接蛋白组成的电突触，这两种连接蛋白在Morone americana（白鲈鱼）中被发现——连接蛋白34.7和连接蛋白35。完成哺乳动物电路调制。通过利用蛋白质诱变，设计一种新的体外系统来分析连接蛋白半通道对接，并对半通道相互作用进行计算建模，课题组人员发现了一个有助于电突触形成的结构基序。

针对这一基序，该研究团队设计了连接蛋白34.7和连接蛋白35半通道，它们相互对接形成电突触，但不与哺乳动物中枢神经系统表达的其他主要连接蛋白对接。该研究组在秀丽隐杆线虫（Caenorhabditis elegans）和小鼠（Mthem mthemculthem）体内验证了这种电突触。研究人员证明它可以加强由不同细胞类型对组成的神经回路之间的通信，并相应地改变行为。在此基础上，该团队建立了“长期集成电路主题连接蛋白”（LinCx），用于哺乳动物的精确电路编辑。

据介绍，不同脑细胞群之间的电信号是认知和情感功能的基础。然而，选择性地调节哺乳动物神经回路的两个细胞组分之间的电信号的方法仍然很少。

附：英文原文

Title: Long-term editing of brain circuits using an engineered electrical synapse

Author: Ransey, Elizabeth, Thomas, Gwenalle E., Wisdom, Elias M., Almoril-Porras, Agustin, Bowman, Ryan, Adamson, Elise, Walder-Christensen, Kathryn K., White, Jesse A., Hughes, Dalton N., Schwennesen, Hannah, Ferguson, Caly, Tye, Kay M., Mague, Stephen D., Niu, Longgang, Wang, Zhao-Wen, Coln-Ramos, Daniel, Hultman, Rainbo, Bursac, Nenad, Dzirasa, Kafui

Issue&Volume: 2026-05-13

Abstract: Electrical signalling across distinct populations of brain cells underpins cognitive and emotional function. However, approaches that selectively regulate electrical signalling between two cellular components of a mammalian neural circuit remain sparse. Here we engineered an electrical synapse composed of two connexin proteins1 found in Morone americana (white perch fish)—connexin34.7 and connexin35—to accomplish mammalian circuit modulation. By exploiting protein mutagenesis, devising a new in vitro system for assaying connexin hemichannel docking, and performing computational modelling of hemichannel interactions, we uncovered a structural motif that contributes to electrical synapse formation. Targeting this motif, we designed connexin34.7 and connexin35 hemichannels that dock with each other to form an electrical synapse but not with other major connexins expressed in the mammalian central nervous system. We validated this electrical synapse in vivo using worms (Caenorhabditis elegans) and mice (Mus musculus). We demonstrate that it can strengthen communication across neural circuits composed of pairs of distinct cell types and modify behaviour accordingly. Thus, we establish ‘long-term integration of circuits using connexins’ (LinCx) for precision circuit editing in mammals.

DOI: 10.1038/s41586-026-10501-y

Source: https://www.nature.com/articles/s41586-026-10501-y