Initial disorder and secondary retinotopic refinement of regenerating axons in the optic tract of the goldfish: signs of a new role for axon collateral loss

The optic tract of the goldfish splits into two brachia just before it reaches the tectum, normal optic axons being distributed systematically between the two according to their retinal origins. The orderliness of this division, like that of the retinotectal projection itself, is conventionally attributed to a system of specific axonal guidance cues. However, the brachial distribution of regenerated axons is much less orderly; and, since there is evidence that these axons have many collateral branches in the nerve and tract, the gross order that remains after regeneration could potentially arise secondarily, in parallel with refinement of the retinotectal map, by a preferential loss of collaterals from the inappropriate brachium. The brachial paths of normal axons, and axons regenerated after optic nerve cut for periods ranging from 19 days to 5 years, were therefore studied by anterograde labelling with horseradish peroxidase from discrete retinal lesions or retrograde labelling of ganglion cells from a cut brachium. From 19 to 28 days, regenerating axons showed little or no preference for their normal brachium. During this period (which includes the first week of tectal synaptogenesis) an average of 46á3% of cells retrogradely labelled from a cut medial brachium were in dorsal retina, compared with only 1á45% in normal fish. Some preference for the normal brachium was evident at 35 days and significant order had returned by 42-70 days, when the average proportion of labelled cells in dorsal retina had fallen to 25á4% though the average number in the whole retina was unchanged. Thus a brachial refinement had occurred in parallel with refinement of the retinotectal map. These results support the idea of a selective loss of axon collaterals from the inappropriate brachium, though they do not exclude the possibility of some concurrent gain in the appropriate one. We suggest that refinement may depend on a process we term 'sibling rivalry': competition between different collaterals of the same axon to form a critical number of stable tectal synapses, in which the most- normally-routed branches have the best chance of succeeding and surviving. Developing normal axons might also make use of collateral formation and 'sibling rivalry' to generate and refine the complex interwoven patterns of the normal optic tract.