IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57445-x.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57445-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57445-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57445-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.