In vivo imaging of central nervous system regeneration using Danionella cerebrum

Rebuilding functional neuronal circuits after injury in the adult central nervous system is unachievable for many vertebrates. In pro-regenerative models, it is unclear how regeneration and rewiring are achieved in the central nervous system over long distances. The size and opacity of the adult vertebrate brain make it difficult to study re-innervation patterns and dynamic cellular interactions during long-distance axon regeneration. Here, we harnessed the properties of the small and transparent adult Danionella cerebrum for longitudinal in vivo imaging of retinal ganglion cell axon regeneration, correlating cellular events with functional recovery. Our results suggest that, following optic nerve injury, the arborization pattern of reinnervation differs after regeneration, suggesting that new axon tracts are formed to restore functional vision. Additionally, myelin is not restored to pre-injury levels, even after functional recovery is achieved. The Danionella cerebrum model provides a unique opportunity to visualize and experimentally manipulate the spatial and temporal events during central nervous system regeneration in intact adult vertebrates.