Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-03-04 DOI:10.1038/s41467-025-57445-x

Xin Zhang, Chao Yang, Chengle Zhang, Junqiang Wu, Xiang Zhang, Jiayang Gao, Xuejie Wang, Leung Ting Chan, Yiren Zhou, Yujun Chen, Sindy Sing Ting Tam, Shuhang Chen, Yuqian Ma, Wing-Ho Yung, Liting Duan, Liwen Jiang, Yiwen Wang, Kai Liu

{"title":"Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement","authors":"Xin Zhang, Chao Yang, Chengle Zhang, Junqiang Wu, Xiang Zhang, Jiayang Gao, Xuejie Wang, Leung Ting Chan, Yiren Zhou, Yujun Chen, Sindy Sing Ting Tam, Shuhang Chen, Yuqian Ma, Wing-Ho Yung, Liting Duan, Liwen Jiang, Yiwen Wang, Kai Liu","doi":"10.1038/s41467-025-57445-x","DOIUrl":null,"url":null,"abstract":"<p>Mechanisms underlying functional axonal rewiring after adult mammalian central nervous system (CNS) injuries remain unclear partially due to limited models. Here we develop a mouse intracranial pre–olivary pretectal nucleus (OPN) optic tract injury model and demonstrate that Pten/Socs3 knockout and CNTF expression in retinal ganglion cells (RGCs) promotes optic tract regeneration and OPN reinnervation. Revealed by transmission electron microscopy, trans-synaptic labeling, and electrophysiology, functional synapses are formed in OPN mainly by intrinsically photosensitive RGCs, thereby partially restoring the pupillary light reflex (PLR). Moreover, combining with Lipin1 knockdown accelerates the recovery and achieves functional reconnection after chronic injury. PLR can be further boosted by increasing RGC photosensitivity with melanopsin overexpression, and it can also be enhanced by treatment of a voltage-gated calcium channel modulator to augment presynaptic release. These findings highlight the importance of neuronal types and presynaptic activity for functional reconnection after CNS injuries.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"9 1","pages":""},"PeriodicalIF":14.7000,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-57445-x","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Mechanisms underlying functional axonal rewiring after adult mammalian central nervous system (CNS) injuries remain unclear partially due to limited models. Here we develop a mouse intracranial pre–olivary pretectal nucleus (OPN) optic tract injury model and demonstrate that Pten/Socs3 knockout and CNTF expression in retinal ganglion cells (RGCs) promotes optic tract regeneration and OPN reinnervation. Revealed by transmission electron microscopy, trans-synaptic labeling, and electrophysiology, functional synapses are formed in OPN mainly by intrinsically photosensitive RGCs, thereby partially restoring the pupillary light reflex (PLR). Moreover, combining with Lipin1 knockdown accelerates the recovery and achieves functional reconnection after chronic injury. PLR can be further boosted by increasing RGC photosensitivity with melanopsin overexpression, and it can also be enhanced by treatment of a voltage-gated calcium channel modulator to augment presynaptic release. These findings highlight the importance of neuronal types and presynaptic activity for functional reconnection after CNS injuries.

Abstract Image

查看原文本刊更多论文

通过亚型和目标特异性轴突再生和突触前活动增强的功能性视神经束重新布线

成年哺乳动物中枢神经系统（CNS）损伤后功能性轴突重新布线的机制仍不清楚，部分原因是模型有限。在这里，我们建立了一个小鼠颅内前视神经节前核（OPN）视束损伤模型，并证明了视网膜神经节细胞（RGC）中的Pten/Socs3敲除和CNTF表达促进了视束再生和OPN再支配。透射电子显微镜、经突触标记和电生理学显示，OPN中的功能性突触主要由固有光敏性RGC形成，从而部分恢复了瞳孔光反射（PLR）。此外，与 Lipin1 基因敲除相结合可加速慢性损伤后的恢复并实现功能性重新连接。通过过表达黑视蛋白提高RGC的光敏性可以进一步促进瞳孔光反射，通过电压门控钙通道调节剂增强突触前释放也可以提高瞳孔光反射。这些发现凸显了神经元类型和突触前活动对中枢神经系统损伤后功能重建的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.