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

Abstract

The emergence of eye-specific axonal projections to the dorsal lateral geniculate nucleus (dLGN) is a well established model system for exploring the mechanisms underlying afferent targeting during development. Using modern tract tracing methods, we examined the development of this feature in the macaque, an Old World Primate with a visual system similar to that of humans. Cholera toxin ␤ fragment conjugated to Alexa 488 was injected into the vitreous of one eye, and CT␤ conjugated to Alexa 594 into the other eye of embryos at known gestational ages. On embryonic day 69 (E69), which is ϳ100 d before birth, inputs from the two eyes were extensively intermingled in the dLGN. However, even at this early age, portions of the dLGN were preferentially innervated by the right or left eye, and segregation is complete within the dorsalmost layers 5 and 6. By E78, eye-specific segregation is clearly established throughout the parvocellular division of the dLGN, and substantial ocular segregation is present in the magnocellular division. By E84, segregation of left and right eye axons is essentially complete, and the six eye-specific domains that characterize the mature macaque dLGN are clearly discernable. These findings reveal that targeting of eye-specific axonal projections in the macaque occurs much earlier and more rapidly than previously reported. This segregation process is completed before the reported onset of ganglion cell axon loss and retino-dLGN synapse elimination, suggesting that, in the primate, eye-specific targeting occurs independent of traditional forms of synaptic plasticity.

Dynamics of Spontaneous Activity in the Fetal Macaque Retina during Development of Retinogeniculate Pathways

“…The results of the present study indicate that retinal waves emerge in the fetal monkey by E60, which is Ͼ1 week before projections from the two eyes begin to segregate in the dlgn (Huberman et al, 2005a). During the developmental period when eye-specific inputs segregate (from E69 to E84), retinal waves decrease markedly in occurrence, becoming progressively less frequent with a concomitant increase in interwave activity.…”

“…The time period during which eyespecific retinogeniculate projections are formed in the fetal monkey has been documented recently using modern axonal tracing methods (Huberman et al, 2005a). This allows one to compare the temporal correspondence between the functional changes in retinal discharge patterns documented in the present study with the segregation of left-and right-eye inputs in the prenatal monkey.…”

“…The gestational period during which visual connections are formed is relatively protracted in the macaque, providing an opportunity to clearly delineate the various cellular processes that occur during visual system development (such as axon outgrowth, target innervation, cell death, etc.). Moreover, previous studies have defined the fetal ages when two hallmark features of the primate visual system are established: the selective ingrowth of magnocellular (M) and parvocellular (P) subsystems (Meissirel et al, 1997) and the segregation of eyespecific ganglion cell inputs to the dlgn (Rakic, 1976;Huberman et al, 2005a) so a comparison of the timing of these events with retinal activity can now be made.…”

Mechanisms Underlying Development of Visual Maps and Receptive Fields

“…In macaques and humans, eye-specific retinogeniculate segregation occurs in the second trimester (Hevner 2000,Huberman et al 2005a,Rakic 1976. In cats this process occurs shortly before birth (E49-60) (Shatz 1983).…”

Visual callosal topography in the absence of retinal input

“…As a result, anophthalmic subjects not only lack postnatal visual experience, but also do not experience (or have much reduced) prenatal retinal “waves” of spontaneous activity as compared to sighted and early blind humans. Comparing these groups offers a way of at least partially separating the influence of pre- and postnatal retinal input on the retinotopic organization of visual connections across hemispheres, and provides an important addition to literature investigating the influence of neuronal activity on the development and maintenance of retinotopic connections between visual hemispheres that has thus far been entirely confined to animal models (Chalupa, 2009; Graven, 2004; Huberman et al, 2005). …”