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

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

SUBMITTER: Zhang X 

PROVIDER: S-EPMC11880380 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature