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

Abstract

In the fetal monkey the projections from the two eyes are initially completely intermingled within the dorsal lateral geniculate nucleus (DLGN) before separating into eye-specific layers (Rakic, 1976). To assess the cellular basis of this developmental process, we examined the morphological properties of individual retinogeniculate axons in prenatal monkeys of known gestational ages. The period studied spanned the time from when binocular overlap has been reported to be maximum, circa embryonic (E) day 77 through E112, when the segregation process is already largely completed in the caudal portion of the nucleus. Retinogeniculate fibers were labeled by making small deposits of DiI crystals into the fixed optic tract. After adequate time was allowed for diffusion of the tracer, fibers were visualized by confocal microscopy, and morphometric measures were made from photomontages. This revealed that retinogeniculate fibers in the embryonic monkey undergo continuous growth and elaboration during binocular overlap and subsequent segregation. Importantly, very few side-branches were found along the preterminal axon throughout the developmental period studied. Thus, restructuring of retinogeniculate fibers does not underlie the formation of eye-restricted projections in the primate. Rather, the results support the hypothesis that binocular segregation in the embryonic monkey is caused by the loss of retinal fibers that initially innervate inappropriate territories (Rakic, 1986). Key words: retinogeniculate projections; primate; prenatal development; terminal arborizations; binocular segregation; dorsal lateral geniculateThe overlap and subsequent segregation of retinogeniculate projections was first demonstrated by Rakic (1976) by means of intraocular injections of tritiated amino acids in fetal monkeys. Since then, the intermingling and later sorting out of binocular inputs has been shown in many species, suggesting that this is a common feature of the mammalian visual system (Chalupa and Dreher, 1991). This developmental process could result from different cellular mechanisms, including the loss of retinal fibers, a retraction of retinogeniculate terminal arbors, and the elimination of axonal side-branches.In the monkey, approximately 3 million ganglion cell axons are generated during fetal development, whereas only approximately 1 million survive to maturity (Rakic and Riley, 1983a). Moreover, the time course of fiber loss corresponds to the period when eye-specific projection patterns become established. This temporal correspondence suggests that the loss of retinal fibers that initially innervate inappropriate eye-specific territories within the geniculate anlage could be responsible for binocular segregation. This hypothesis is f urther supported by the finding that removal of one eye during the binocular overlap period results in a significant increase in the number of fibers in the remaining optic nerve and an expanded retinogeniculate projection from the remaining eye (Rakic and Riley, 1983b;Rakic, 1986).There...

Early and Rapid Targeting of Eye-Specific Axonal Projections to the Dorsal Lateral Geniculate Nucleus in the Fetal Macaque

“…Thus, eye-specific segregation parallels only the earliest stages of ganglion cell arbor formation. Also, whereas in the cat, pruning of axonal side branches coincides with eye segregation (Sretavan and Shatz, 1984) and is dependent on binocular competition (Garraghty et al, 1988), in the fetal monkey, retinogeniculate axons never exhibit side branches (Snider et al, 1999), and monocular enucleation does not influence the size of retinogeniculate arbors stemming from the remaining eye (Wefers et al, 2000).…”

“…org as supplemental material). In fetal monkey, retinogeniculate arbors undergo progressive growth beginning on ϳE77 and until E140ϩ (Snider et al, 1999). Thus, eye-specific segregation parallels only the earliest stages of ganglion cell arbor formation.…”

“…Furthermore, much is known about the major developmental events in the embryonic macaque visual system, including the timing of retinal ganglion cell and dLGN cell birth and matura-tion (Rakic, 1977a;Shatz and Rakic, 1981;La Vail et al, 1991), the attrition of optic nerve axons (Rakic and Riley, 1983), the ingrowth and elaboration of retinogeniculate axons (Meissirel et al, 1997;Snider et al, 1999), and synapse formation in the dLGN (Hendrickson and Rakic, 1977). Because Rakic's study relied on tracers now known to be prone to "spillover" (LeVay et al, 1978;Ruthazer et al, 1999;Crair et al, 2001) and long postinjection survival periods, a precise delineation of when eye segregation occurs in this important model species is lacking.…”

Development of Individual Axon Arbors in a Thalamocortical Circuit Necessary for Song Learning in Zebra Finches

“…For example, adult patterns of connec- tivity within developing sensory systems emerge as a result of extensive elaboration of axonal branches within restricted regions of postsynaptic targets. This increase in the number of axonal branches is accompanied by the elimination of a relatively small number of branches within "inappropriate" areas Shatz, 1984, 1986;Young and Rubel, 1986;Callaway and Katz, 1991;Agmon et al, 1993;Antonini and Stryker, 1993;Catalano et al, 1996;Snider et al, 1999). Thus, nascent axon arbors tend to be simple in shape and restricted in extent, and initial axonal connections can be extremely specific (Crowley and Katz, 1999).…”

Mapping Labels in the Human Developing Visual System and the Evolution of Binocular Vision

“…In particular, the development of primate retinal topography and eye segregation, unlike in the cat or ferret for instance, seems to be characterized by an early emergence of fiber ordering, with little exuberance and pruning (Chalupa et al, 1996;Meissirel et al, 1997;Snider et al, 1999;Wefers et al, 2000), raising further the question of the evolutionary conservation of the mechanisms of development of retinal projections.…”