Synaptic organization of regenerated retina in the goldfish

In the adult goldfish, any manipulation that significantly depletes retinal neurons stimulates neurogenesis and the regeneration of nearly normal retina. We sought to determine the extent to which the regenerated neurons formed normal synaptic connections. We used qualitative and quantitative electron microscopy to compare the organization of the synaptic layers in regenerated and normal retinas. In eight eyes, a small patch of retina was surgically excised, stimulating regeneration of new retina in its place. Animals were killed 16-20 weeks after surgery. Qualitative comparisons of the synaptic architecture of photoreceptor terminals in the outer plexiform layer and quantitative comparisons of the synaptic organization in the inner plexiform layer were made between the patch of regenerated retina and an adjacent intact site. In the regenerated outer plexiform layer, cone pedicles and rod spherules were not arranged as regularly as normal, but they formed normal-appearing synaptic contacts. In the regenerated inner plexiform layer, with one exception, the quantitative descriptors of the synaptic organization in the normal and regenerate were not significantly different: The planimetric and numerical densities of the synapses, number of synapses/inner retinal neuron, and, with the exception of the bipolar terminals in the inner plexiform layer, and synapse depth profiles were similar. These data suggest that 1) relatively normal synaptic connections are recreated during regeneration, 2) the cellular mechanisms that guide synaptogenesis during development act during retinal regeneration, and 3) the physiological response properties of regenerated neurons should be comparable to that found in the normal retina.