In vivo imaging of central nervous system regeneration using Danionella cerebrum

Rebuilding functional neuronal circuits after injury in the adult central nervous system (CNS) is unachievable for many vertebrates. In pro-regenerative models, it is unclear how regeneration and re-wiring is achieved in the CNS over long distances. The size and opacity of the adult vertebrate brain makes 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 re-innervation 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 D. cerebrum model provides a unique opportunity to visualize and experimentally manipulate the spatial and temporal events during CNS regeneration in intact adult vertebrates. Research highlightsO_LIReveals the neuro-regenerative potential of the small, transparent adult vertebrate C_LIO_LIDanionella cerebrum, a novel model for central nervous system (CNS) repair studies. C_LIO_LIDemonstrates CNS regeneration using two visual functional recovery assays and longitudinal in vivo imaging of a novel adult axonogenesis reporter transgenic line, a myelin reporter line, and mosaic labeling of retinal ganglion cell axons. C_LIO_LIEstablishes a method to compare retinal ganglion cell axons before and after CNS injury in adult D. cerebrum. C_LIO_LIPositions D. cerebrum as a powerful platform for visualizing long-distance CNS regeneration in intact adult vertebrates. C_LI Graphical abstractLongitudinal live imaging of adult D. cerebrum reveals the formation of a new axon and myelin pattern post optic nerve injury along with functional recovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/653880v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@15b5962org.highwire.dtl.DTLVardef@494f5forg.highwire.dtl.DTLVardef@fa1c7corg.highwire.dtl.DTLVardef@644bdd_HPS_FORMAT_FIGEXP M_FIG C_FIG