Development of connections in the human visual system during fetal mid-gestation: a DiI-tracing study

Animal studies have shown that connections between the retina, lateral geniculate nucleus (LGN), and visual cortex begin to develop prenatally. To study the development of these connections in humans, regions of fixed brain from fetuses of 20-22 gestational weeks (GW) were injected with the fluorescent tracer DiI. Placement of DiI in the optic nerve or tract labeled retinogeniculate projections. In the LGN, these projections were already segregated into eye-specific layers by 20 GW. Retinogeniculate segregation thus preceded cellular lamination of the LGN, which did not commence until 22 GW. Thalamocortical axons, labeled from DiI injections into the optic radiations, densely innervated the subplate, but did not significantly innervate the cortical plate. This pattern was consistent with observations of a "waiting period" in animals, when thalamocortical axons synapse in the subplate for days or weeks before entering the cortical plate. Cortical efferent neurons (labeled retrogradely from the optic radiations) were located in the subplate and deep layers of the cortical plate. In summary, human visual connections are partially formed by mid-gestation, and undergo further refinement during and after this period. The program for prenatal development of visual pathways appears remarkably similar between humans and other primates.