The retinotopic map of visual space in the optic tectum is the best characterized of all these maps. How does it arise? A famous experiment in the 1940s on frogs provided an important clue. If the optic nerve of a frog is cut, it will regenerate. The retinal axons grow back to the optic tectum, restoring normal vision. If, however, the eye is in addition rotated in its socket at the time of cutting of the nerve, so as to put originally ventral retinal cells in the position of dorsal retinal cells, vision is still restored, but with an awkward flaw: the animal behaves as though it sees the world upside down and left–right inverted (Figure 21–77). If food is dangled in front of it, for example, it will lunge perversely backward. This is because the misplaced retinal cells make the connections appropriate to their original, not their actual, positions. It seems that the retinal ganglion cells (RGCs) have positional values—position-specific biochemical properties representing records of their original location in the retina, assigned perhaps by earlier morphogen gradients, and making RGCs on opposite sides of the retina intrinsically different.
Such nonequivalence among neurons is referred to as neuronal specificity. It is this intrinsic characteristic that guides the retinal axons to their appropriate target sites in the tectum. Those target sites themselves are distinguishable by the
Figure 21–77 Neurons in different regions of the retina project axons  to different regions in the tectum.
Neurons (rGcs) in the anterior retina project axons to the posterior tectum (as shown in Figure 21–75 for zebrafish).
regeneration experiments show that retinal neurons have an intrinsic preference for the part of the tectum they normally connect to. If the eye is surgically rotated when the optic nerve is cut, the regenerating retinal axons connect to their original targets, creating an inverted map. (after e. Kandel et al., principles of Neural Science, 5th ed., New York: McGraw hill Medical, 2012.)
Figure 21–78 Selectivity of retinal axons growing over tectal membranes. (a) Diagram of an experiment performed with cells from a chick embryo. the culture substratum is coated with alternating stripes of membrane prepared either from posterior tectum or from anterior tectum. axons from posterior retina grow on anterior tectal membrane but are repelled by posterior tectal membrane. axons from anterior retina show different (less selective) behavior. (B) photograph of results. the retinal axons, growing out from the left, are made visible by staining them with a fluorescent marker. the selective pattern of outgrowth shows that anterior tectum differs from posterior tectum, and anterior retina correspondingly differs from posterior retina. In the intact organism, this serves to orient a retinotopic map; the map is refined by subsequent competitive interactions among the anterior and posterior retinal axons, which push the anterior retinal cells off anterior tectal territory. (From J. Walter et al., Development 101:685–696, 1987.With permission from the company of Biologists.) retinal axons because the tectal cells also carry positional labels. Thus, the neural map depends on a correspondence between two systems of positional markers, one in the retina and the other in the tectum.
How are these markers used to make the map? When posterior axons are allowed to grow out over a carpet of anterior or posterior tectal membranes in a culture dish, they show selectivity. Posterior axons strongly prefer the anterior tectal membranes, as in vivo, whereas anterior axons show no preference or prefer posterior tectal membranes (Figure 21–78). The key difference between anterior and posterior tectum is not an attractive factor on the anterior tectum but a repulsive factor on the posterior tectum, to which posterior retinal axons are sensitive but anterior retinal axons are not. If a posterior retinal growth cone touches posterior tectal membrane, it collapses its filopodia and withdraws.