The development of the isthmo‐optic tract in the chick, with special reference to the occurrence and correction of developmental errors in the location and connections of isthmo‐optic neurons

The development of the centrifugal projection to the chick retina in the isthmo‐optic tract (IOT) has been studied by the retrograde transport of the enzyme marker horseradish peroxidase (HRP) injected into the eye at various times during the incubation period. Some neurons in the isthmo‐optic nucleus (ION — the cells of origin of the IOT) can first be labeled from the eye following injections on the tenth day of incubation; after injections on the twelfth day or later, about 95% of the neurons can be so labeled. It follows from this that the axons of virtually all the neurons in the ION (including the 60% which normally degenerate between the thirteenth and seventeenth days of incubation) reach the contralateral eye. Since in 12‐day old embryos the IOT is between six and seven millimeters in length and HRP can be identified in the perikarya of ION neurons within three and one‐half hours, the rate of retrograde transport in the system must be of the order of 48 mm/day. A similar time is required for HRP to appear in the perikarya of ION neurons in post‐hatched chicks in which the length of the IOT is estimated to be about 14 mm. This suggests that at some time during the latter half of the incubation period there is a significant acceleration in the rate of retrograde transport, similar to that found for anterograde axonal transport in the chick and rabbit visual systems. In addition to labeling neurons in the contralateral ION, intraocular injections of HRP before the sixteenth day of incubation label a significant number of cells (up to 650) which lie outside the borders of the nucleus, and a small number (10–100) in the ipsilateral ION. About 90% of the ectopic neurons and all of the cells in the ION which send their axons aberrantly into the ipsilateral eye, degenerate some time after the fifteenth day of incubation, apparently because they either do not make appropriate connections within the retina or else fail to receive an appropriate input from the optic tectum. After early removal of one optic cup, the number of neurons in the ipsilateral ION that can be labeled by HRP injected into the surviving eye is greatly increased (involving as many as 50% of the cells in the nucleus). Despite the fact that the axons of these cells reach the retina (albeit of the “wrong” side) the cells do not survive beyond the seventeenth day of incubation. However, during the period in which their axons are in the retina they appear to interfere with synapse formation by the axons of the neurons in the contralateral (“correct”) ION; only about half the normal number of ION neurons survive under these circumstances. These findings suggest: (i) that certain types of errors may be common during neural development, (ii) that they are generally transitory, being recognized and eliminated at later stages in development, and (iii) that although transitory, some errors may have long lasting sequelae.