Intraocular colchicine inhibits competition between resident and foreign optic axons for functional connections in the doubly innervated goldfish optic tectum

After unilateral optic tectum ablation in the goldfish, regenerating optic axons grow into the optic layers of the remaining ipsilateral tectal lobe and regain visual function. The terminal arbors of the foreign fibers are initially diffusely distributed among the resident optic axons, but within two months the axon terminals from each retina are seen to segregate into irregular ocular dominance patches. Visual recovery is delayed until after segregation. This suggests that the foreign fibers compete with the residents for tectal targets and that the segregation of axon terminations is an anatomical characteristic of the process. Here we investigate whether inhibiting axonal transport in the resident fibers inhibits competition with foreign fibers. The eye contralateral to the intact tectal lobe received a single injection of 0.1 μg colchicine, which does not block vision with the intact eye. We measured visual function using a classical conditioning technique. Segregation of axon terminations was examined shortly following visual recovery by autoradiography. The no-drug control fish showed reappearance of vision with the experimental eye at 9 weeks postoperatively and ocular dominance patches were well developed. Colchicine administered to the intact eye (resident fibers) several weeks postsurgery decreased the time to reappearance of vision with the experimental eye by several weeks. Autoradiography revealed some signs of axonal segregation but the labeled foreign axons were mainly continuously distributed. Administration of colchicine at the time of tectum ablation, or of lumicolchicine at two weeks postoperatively produced normal visual recovery times. Fast axonal transport of³H-labeled protein was inhibited by 1.0 and 0.5 μg but not by 0.1 μg of colchicine or by 1.0 μg of lumicolchicine. Previous studies showed that while 0.1 μg of colchicine does not block vision it is sufficient to inhibit axonal regeneration following optic nerve crush. We conclude that two retinas can functionally innervate one tectum without forming conspicuous ocular dominance columns, and that the ability of residents to compete with the in-growing foreign axons is very sensitive to inhibition of axoplasmic transport or other processes that are inhibited by intraocular colchicine.