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 process, presumed to be some form of substrate-directed growth, which generates rough retinotopy as seen in the early formed projection. The other is an activity-dependent process that generates fine retinotopy during 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 compressing into the available tectal space while preserving retinotopic order. These plasticities can dramatically alter the scale of the projection. The other behavior is the formation of fixed synaptic sites in tectum. Optic fibers make a characteristic number of synaptic connectionsin tectum, which is not changed by increasing the number of invading optic, fibers. This has been interpreted to mean that fibers compete for limited synaptic sites. How the two processes that generate order, substrate-directed growth, and activity-dependent refinement might each be affected by the expression of retinotopic plasticity and altered synaptic competition is largely unknown. In particular, it is not known how fine retinotopic order (activity-dependent refinement) might be affected by altering the scale of the projection. Would optic fibers from neighboring ganglion cells converge into the same-sized area of tectum, or would they expand or compress in proportion to the altered scale of the overall map? To explore this issue, the posterior half of tectum of goldfish was removed, and the optic nerve was crushed, thereby forcing regenerating fibers to form a compressed retinotopic projection onto the anterior half of tectum. Under these conditions, optic fibers are also forced to compete for half the normal number of synaptic sites. The effect on retinotopy was monitored at various times during regeneration by making a small spot injection of wheat germ agglutinin-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-independent processes, retinal impulse activity was blocked in some animals by repeated intraocular injections of tetrodotoxin. The initial projection was found to be unaffected by impulse activity. Regardless of activity, nasal fibers failed initially to grow to the most posterior available regions, but instead were the “incorrect” anterior half of tectum at 30 days. Under activity dispersed across much of the blockade, compressed retinotopy was subsequently generated by a progressive improvement of this initially dispersed projection over the next 2 months, but this retinotopy was impaired compared to that formed during regeneration into an intact tectum under activity blockade. Surprisingly, with impulse activity, the amount of refinement was normal in that fibers labelled 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 whole was. This indicates that fine retinotopic order, as measured by the convergence of neighboring retinal ganglion cells, is relatively constant in spite of large changes in the scale of the overall projection. © 1994 Wiley-Liss, Inc.