Targeting and activity-related dendritic modification in mammalian retinal ganglion cells

We have studied factors that influence the development of dendritic morphology in hamster retinal ganglion cells. By combining fluorescent retrograde tracing with in vitro Lucifer yellow injection into fixed retina, cells with appropriate and inappropriate visuotopic projections have been compared. In adult hamsters, cells with an aberrant ipsilateral projection from the nasal retina display a uniformly sparse dendritic morphology. However, following monocular enucleation at postnatal day 0 (P0), this population displays a significantly enhanced dendritic complexity in the adult. By contrast, removal of one eye at P6 or at P12 produces progressively less effect. These results suggest that dendritic complement of the adult aberrant projection can be regulated by altering the early postnatal axonal environment. The development of aberrant ganglion cells was investigated to determine the relative influences of cell death and dendritic remodeling in shaping the composition of the adult aberrant population. Aberrant cells were found to be indistinguishable from other cells in nasal retina throughout early development. After ganglion cell death (P1-P12) is over, aberrant cells still display a full range of cell types. However, at eye opening (P16) they undergo a rapid loss of dendritic complexity by remodeling. By P22, aberrant cells display a uniformly sparse dendritic morphology. When hamsters were raised in the dark between P12 (the end of ganglion cell death) and P22, this severe remodeling was blocked. This block was maintained when hamsters were dark reared to P42. Hence, both dark rearing and monocular enucleation at P0 produce similar effects on the development of visuotopically inappropriate hamster retinal ganglion cells. We speculate that the patterns of dendritic sculpting that we have observed reflect activity-mediated modulation of dendritic form via retrograde signals from the terminal arbors. This has implications for retinal ganglion cell morphological classification and, more generally, for mechanisms that influence the dendritic development of other neurons in the CNS.