Selective innervation of retinorecipient brainstem nuclei by retinal ganglion cell axons regenerating through peripheral nerve grafts in adult rats

The pattern of axonal regeneration, specificity of reinnervation, and termi nal arborization in the brainstem by axotomized retinal ganglion cell axons was studied in rats with peripheral nerve grafts linking the retina with i psilateral regions of the brainstem, including dorsal and lateral aspects o f the diencephalon and lateral aspect of the superior colliculus. Four to 1 3 months later, regenerated retinal projections were traced using intraocul ar injection of cholera toxin B subunit. In approximately one-third of the animals, regenerated retinal axons extended into the brainstem for distance s of up to 6 mm. Although axons followed different patterns of ingrowth dep ending on their site of entry to the brainstem, within the pretectum, they innervated preferentially the nucleus of the optic tract and the olivary pr etectal nucleus in which they formed two types of terminal arbors. Within t he superior colliculus, axons extended laterally and formed a different ter minal arbor type within the stratum griseum superficiale. In the remaining two-thirds of the animals, retinal fibers formed a neuroma-like structure a t the site of entry into the brainstem, or a few fibers extended for very s hort distances within the neighboring neuropil. These experiments suggest t hat regenerated retinal axons are capable of a highly selective reinnervati on pattern within adult denervated retinorecipient nuclei in which they for m well defined terminal arbors that may persist for long periods of time. I n addition, these studies provide the anatomical correlate for our previous functional study on the re-establishment of the pupillary light reflex in this experimental paradigm.