NORMAL ACTIVITY-DEPENDENT REFINEMENT IN A COMPRESSED RETINOTECTAL PROJECTION IN GOLDFISH

When the optic nerve in a goldfish is crushed, regenerating fibers can reform a normal retinotopic projection. Two processes are thought to generate this retinotopic order. One is an activity-independent proces s, presumed to be some form of substrate-directed growth, which genera tes rough retinotopy as seen in the early formed projection. The other is an activity-dependent process that generates fine retinotopy durin g a protracted period of refinement. This projection also displays two other behaviors. One is retinotopic plasticity, in which optic fibers can compensate for retinal or tectal ablations by expanding or compre ssing into the available tectal space while preserving retinotopic ord er. These plasticities can dramatically alter the scale of the project ion. The other behavior is the formation of fixed synaptic sites in te ctum. Optic fibers make a characteristic number of synaptic connection s in tectum, which is not changed by increasing the number of invading optic fibers. This has been interpreted to mean that fibers compete f or limited synaptic sites. How the two processes that generate order, substrate-directed growth, and activity-dependent refinement might eac h be affected by the expression of retinotopic plasticity and altered synaptic competition is largely unknown. In particular, it is not know n how fine retinotopic order (activity-dependent refinement) might be affected by altering the scale of the projection. Would optic fibers f rom neighboring ganglion cells converge into the same-sized area of te ctum, or would they expand or compress in proportion to the altered sc ale of the: overall map? To explore this issue, the posterior half of tectum of goldfish was removed, and the optic nerve was crushed, there by forcing regenerating fibers to form a compressed retinotopic projec tion onto the anterior half of tectum. Under these conditions, optic f ibers are also forced to compete for half the normal number of synapti c sites. The effect on retinotopy was monitored at various times durin g regeneration by making a small spot injection of wheat germ agglutin in-horseradish peroxidase (WGA-HRP) into nasal retina corresponding to fibers that would normally terminate in the missing posterior half of tectum. To distinguish between activity-dependent and activity-indepe ndent processes, retinal impulse activity was blocked in some animals by repeated intraocular injections of tetrodotoxin. The initial projec tion was found to be unaffected by impulse activity. Regardless of act ivity, nasal fibers failed initially to grow to the most posterior ava ilable regions, but instead were dispersed across much of the ''incorr ect'' anterior half of tectum at 30 days. Under activity blockade, com pressed retinotopy was subsequently generated by a progressive improve ment of this initially dispersed projection over the next 2 months,but this retinotopy was impaired compared to that formed during regenerat ion into an intact tectum under activity blockade. Surprisingly, with impulse activity, the amount of refinement was normal in that fibers l abelled by the retinal spot injections eventually formed a projection that was the same size and shape as that seen in a normal tectum. Fine retinotopy was not obviously compressed, even though the map as a who le was. This indicates that fine retinotopic order, as measured by the convergence of neighboring retinal ganglion cells, is relatively cons tant in spite of large changes in the scale of the overall projection. (C) 1994 Wiley-Liss, Inc.