The Development of the Isthmo-Optic Nucleus; pp. 345–359

Abstract

The nucleus of origin of centrifugal fibers to the retina (the so-called isthmo-optic nucleus – ION) has been used as a model for the study of the major features of neural development, from the period of cell proliferation until after the formation of its afferent and efferent connections. ³H-thymidine autoradiography has established that in the chick the cells of the ION are generated (i.e., become post-mitotic) between the middle of the 5th and the end of the 7th days of incubation. The first-formed cells are found in the ventrolateral part of the nucleus, while those that are generated at successively later stages come to occupy progressively more medial and dorsal positions within the nucleus. The anlage of the ION can be identified on the 8th day of incubation, and by the 11th day, when it is numerically complete, it occupies a prominent position in the caudo-dorsal part of the midbrain tegmentum at the level of the IVth nerve nucleus. At this stage the nucleus contains about 22,000 neurons, and shows no signs of cytoarchitectonic differentiation. Between the 13th and 17th days of incubation, about 60% of the neurons in the nucleus degenerate; as a result of this degeneration, the arrival of afferent fibers, and the growth of the cells'' processes, the nucleus comes to have its characteristic adult form of a complex, folded, bilaminar sheet, in which each part of the retina is precisely represented. Experiments based on the retrograde transport of horseradish peroxidase (HRP) from the eye indicate that the first centrifugal fibers, in the isthmo-optic tract (IOT), reach the retina on the 10th day of incubation, and by the 12th day all but about 5% of the neurons in the ION can be retrogradely labeled in this way. Thus, prior to the onset of the naturally occurring cell loss in the nucleus, virtually all the cells have sent axons to the retina. Removal of the optic cup on the 3rd day of incubation has no effect upon the development of the ION until the 13th day when there is a marked accentuation of the phase of naturally occurring cell loss, so that by the 17th day of incubation no cells remain within the ION. After partial lesions of the optic vesicle before stage 11 (early on the 2nd day of incubation) the nucleus is much reduced in size but all four retinal quadrants appear to be represented since, although the ION is much reduced in size it seems to retain its overall morphology. This suggests that the small eyes that result from these early lesions have regulated and hence are able to receive a retino-topically organized centrifugal input. Comparable lesions after stage 11 (when the axial polarity of the retina is established) resulted in a severe cell loss in the region of the ION related to the ablated portion of the neural retina. The time course of these superadded degenerations in the ION seems to parallel that of the naturally occurring cell loss; this implies that the latter may be due to the inability of 60% of the neurons in the ION to either make synaptic connections in the retina or to make a sufficient number to maintain the viability of the cells. Partial lesions of the optic tectum on the 5th day of incubation also lead to degeneration in the corresponding sector(s) of the ION. It is evident from this that neurons in the ION are also dependent upon their afferent input for their survival. During the normal development of the ION, two types of systematic error occur. First, as many as 700 neurons migrate to ectopic loci ventral to the ION, but nevertheless succeed in sending their axons to the contralateral eye. Between 80 and 90% of these ectopic neurons degenerate during the period of naturally occurring cell loss. Second, up to 100 neurons in the ION may send their axons aberrantly to the ipsilateral retina. Normally, all such neurons with aberrant axons degenerate. In animals from which one optic cup had been removed, more than 50% of the neurons in the ION have been found to send their axons to the wrong eye. Again, all these cells with aberrant axons degenerate by the 17th day of incubation. However, during the period in which their axons are present in the retina they appear to interfere with the formation of synapses by the axons from the contralateral ION. As a result of this, an additional 50% of the neurons in the ION of the control sides degenerate during the period of naturally occurring cell loss.