Age-dependent remodelling of retinal circuitry.

We have investigated morphological changes in second-order neurons of the mouse retina during aging by using immunohistochemistry and electron microscopy. We observed sprouting of rod bipolar cells dendrites and horizontal cells arborizations: neuronal processes of both neuronal types showed irregular extensions beyond the outer plexiform layer, toward the outer limiting membrane, as well as into the outer nuclear layer (ONL). These processes were first observed in animals of 12 months of age and increased in numbers steadily until 24 months, which represent the last age examined. The ectopic processes are decorated by puncta immunoreactive for pre-synaptic markers typical of photoreceptor terminals juxtaposed to post-synaptic neurotransmitter receptors, demonstrating the presence of the entire molecular machinery of functional synapses. Electron microscopy confirmed that ectopic processes receive synapses from photoreceptor terminals. We conclude that during the second year of life retinal rod bipolar and horizontal cells undergo sprouting and form ectopic synapses in the ONL.