Loss of axons in the cat optic nerve following fetal unilateral enucleation: an electron microscopic analysis

Abstract

Between the 48th day of gestation (E-48) and maturity, the number of axons in the cat optic nerve is reduced by approximately 50%. On the basis of an electron microscopic assay, the axon population of the E-48 nerve was estimated to be 328,000. In contrast, estimates from two normal adults were 159,000 and 158,000. In utero unilateral enucleation (at E-45 and E-46) attenuated the severity of this loss since the optic nerves of the experimental animals contained 200,000 and 198,000 fibers. These results indicate that prenatal binocular competition is involved in the elimination of ganglion cell axons during the normal development of the cat's visual system. The increased number of axons in the optic nerve of the prenatally enucleated animals could be due to reduced ganglion cell death or a failure to retract supernumerary axon collaterals. It is suggested that the former explanation is more consistent with what is currently known about the development of retinofugal projections.Early in development,, retinal projections to the dorsal lateral geniculate nucleus and the superior colliculus are diffuse (Rakic, 1976(Rakic, , 1977 Cavalcante and Rocha-Miranda, 1978; Frost et al., 1979; Land and Lund, 1979;Linden et al., 1981;Williams and Chalupa, 1982a), whereas the mature connections are characterized by distinct ocular dominance domains and an exquisite topography. The mechanisms which underlie this remarkable transformation are unknown. However, recent studies suggest that cell death may contribute to the development of the mammalian visual system and, in particular, to the refinement of patterns of connection (Cunningham et al., 1979(Cunningham et al., , 1981 Jeffery and Perry, 1981; Finlay, 1981, 1982;Stone et al., 1982). If ganglion cell death underlies the restructuring of retinal projections that we and others have recently demonstrated in the cat (Shatz and DiBerardino, 1980; Kliot and Shatz, 1981; Chalupa, 1980, 1981 1982a), then the optic nerve of the fetus must contain a greater number of fibers than that of the adult. Furthermore, if this attrition is related to axon-target interactions, then prenatal unilateral enucleation should attenuate the severity of in ,utero retinal cell loss since the number of potential postsynaptic target sites available to axons of the spared ey8 could be doubled (cf. Rakic, 1979). The results of th8 present study are consistent with both of these ideas. We have found a significant attrition in the population of retinal ganglion cell axons during normal development. This loss is attenuated by the elimination of prenatal binocular competition. Materials and MethodsFive cats were used in this study. Two were normal adults: a lo-month-old 2.5-kg female tabby and an 18-month-old 3.8-kg black and white male. The two experimental animals had one eye removed more than 2 weeks before their natural birth, one on embryonic day 45 (E-45), the other on day E-46, and were both born on the 63rd day of gestation. These unilateral enucleates were males with black and white coats. Th...

Postnatal development of the rat dorsal funiculus

“…A decline of similar magnitude was reported by Koppel and Innocenti (1983): 70% of callosal axons present at birth were eliminated by adulthood. Similarly, there is a significant reduction in the number of corticospinal axons after birth (Reh and Kalil, 1982) and of optic axons in neonates and after birth (Ng and Stone, 1982;Rakic and Riley, 1983;Williams et al, 1983Williams et al, , 1986. It is unlikely that losses of this magnitude could be explained solely on the basis of cell death, especially since few neurons are supposed to be lost after birth; however, there has been debate as to whether some sympathetic cells are lost postnatally (Hendry and Campbell, 1976;Davies, 1978;Smolen et al, 1983) and there are reports of cell death in the cerebral cortex after birth (Pearlman, 1984).…”

Prenatal Development of Retinogeniculate Axons in the Macaque Monkey during Segregation of Binocular Inputs

“…Additionally, an E50 fetal cat was used to obtain comparative information. The in utero surgical procedures for harvesting fetal cat tissue have been described in detail in previous publications (Williams et al, 1983;Chalupa et al, 1984).…”

“…Indeed, in both species the ingrowth of axons appears highly directed, and the formation of terminal arbors seems well defined. Moreover, in carnivores as in primates, there is a massive loss of optic fibers during the period when separation of left and right eye projections is occurring (Williams et al, 1986), and removal of one eye in a fetal cat during this period results in a significant increase in the number of optic fibers and retinal ganglion cells in the remaining eye (Williams et al, 1983;Chalupa et al, 1984). So why are axonal side-branches relatively common on retinogeniculate fibers of the fetal cat and so uncommon in the fetal monkey?…”

Functional organization of the cat's visual cortex after prenatal interruption of binocular interactions.

“…Procedures used to time gestational age and the surgical methods used to enucleate one eye of fetal cats have been described in previous publications from this laboratory (14,16,18). In brief, anesthesia was induced in pregnant cats with 4% halothane vapor in oxygen.…”

“…In turn, principal cells of the LGd ofprenatally enucleated cats and monkeys innervate layer IV of the visual cortex in a continuous rather than an alternating pattern (13,15). In addition, prenatal unilateral enucleation attenuates naturally occurring ganglion cell and axon loss in the remaining retina and optic nerve and prevents the formation of distinct cell laminae in the LGd (13,(16)(17)(18).…”