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

Author

Listed:
  • Xin Zhang

    (The Hong Kong University of Science and Technology)

  • Chao Yang

    (The Hong Kong University of Science and Technology
    Hong Kong Center for Neurodegenerative Diseases
    Shenzhen Peking University–The Hong Kong University of Science and Technology Medical Center
    HKUST Shenzhen Research Institute; Shenzhen-Hong Kong Institute of Brain Science)

  • Chengle Zhang

    (The Hong Kong University of Science and Technology)

  • Junqiang Wu

    (The Hong Kong University of Science and Technology)

  • Xiang Zhang

    (The Hong Kong University of Science and Technology
    The Hong Kong University of Science and Technology)

  • Jiayang Gao

    (The Chinese University of Hong Kong)

  • Xuejie Wang

    (The Hong Kong University of Science and Technology
    Hong Kong Center for Neurodegenerative Diseases)

  • Leung Ting Chan

    (The Hong Kong University of Science and Technology)

  • Yiren Zhou

    (The Hong Kong University of Science and Technology)

  • Yujun Chen

    (The Hong Kong University of Science and Technology)

  • Sindy Sing Ting Tam

    (The Hong Kong University of Science and Technology
    The Hong Kong University of Science and Technology)

  • Shuhang Chen

    (Hong Kong Center for Neurodegenerative Diseases
    The Hong Kong University of Science and Technology)

  • Yuqian Ma

    (University of Science and Technology of China)

  • Wing-Ho Yung

    (City University of Hong Kong)

  • Liting Duan

    (The Chinese University of Hong Kong)

  • Liwen Jiang

    (The Chinese University of Hong Kong)

  • Yiwen Wang

    (The Hong Kong University of Science and Technology
    The Hong Kong University of Science and Technology)

  • Kai Liu

    (The Hong Kong University of Science and Technology
    Hong Kong Center for Neurodegenerative Diseases
    Shenzhen Peking University–The Hong Kong University of Science and Technology Medical Center
    HKUST Shenzhen Research Institute; Shenzhen-Hong Kong Institute of Brain Science)

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.

Suggested Citation

  • 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 Yun, 2025. "Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57445-x
    DOI: 10.1038/s41467-025-57445-x
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    References listed on IDEAS

    as
    1. Fang Sun & Kevin K. Park & Stephane Belin & Dongqing Wang & Tao Lu & Gang Chen & Kang Zhang & Cecil Yeung & Guoping Feng & Bruce A. Yankner & Zhigang He, 2011. "Sustained axon regeneration induced by co-deletion of PTEN and SOCS3," Nature, Nature, vol. 480(7377), pages 372-375, December.
    2. Ali D. Güler & Jennifer L. Ecker & Gurprit S. Lall & Shafiqul Haq & Cara M. Altimus & Hsi-Wen Liao & Alun R. Barnard & Hugh Cahill & Tudor C. Badea & Haiqing Zhao & Mark W. Hankins & David M. Berson &, 2008. "Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision," Nature, Nature, vol. 453(7191), pages 102-105, May.
    3. Noemie Vilallongue & Julia Schaeffer & Anne-Marie Hesse & Céline Delpech & Béatrice Blot & Antoine Paccard & Elise Plissonnier & Blandine Excoffier & Yohann Couté & Stephane Belin & Homaira Nawabi, 2022. "Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    4. Yi Li & Xuelian He & Riki Kawaguchi & Yu Zhang & Qing Wang & Aboozar Monavarfeshani & Zhiyun Yang & Bo Chen & Zhongju Shi & Huyan Meng & Songlin Zhou & Junjie Zhu & Anne Jacobi & Vivek Swarup & Philli, 2020. "Microglia-organized scar-free spinal cord repair in neonatal mice," Nature, Nature, vol. 587(7835), pages 613-618, November.
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