Development of Connections in the Human Visual System During Fetal Mid-Gestation: A Dil-Tracing Study

Abstract

Abstract. 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.

Unravelling the development of the visual cortex: implications for plasticity and repair

“…Their work has demonstrated the temporal profile of connection of the thalamocortical axons during the 'waiting period' (a period when thalamocortical axons synapse in the subplate for days or weeks before entering the cortical plate) in the subplate and subsequent engagement with the cortical plate close to birth (reviewed in Kostovic & Judas, 2010). In another study of midgestational tissues looking specifically at the development of connections in the human visual system, it was demonstrated that human visual connections are partially formed by mid-gestation, and undergo further refinement during and after this period (Hevner, 2000). Also, an earlier study by Kostovic and Rakic (Kostovic & Rakic, 1984) revealed the spatiotemporal profile of development of the afferent connections originating in the pulvinar nucleus of the thalamus to the extrastriate cortex (Brodmann's areas 18,19,20,21) in both monkey and human.…”

Pain Assessment in Human Fetus and Infants

“…Therefore, most authors have argued that fetal pain can be experienced during the third trimester (70) second trimester (71) or after 20 weeks of gestational age (72). Given the uncertainty about the gestational age when pain can be experienced, the precautionary principle points to a need to use analgesic treatments (73)(74)(75) since when the neural connections between peripheral receptors, the thalamus, and the cortical subplate the basis for pain perception appear at about 20-22 weeks from conception (76,77). Unfortunately, no pain scales exist to date for the evaluation of fetal pain.…”

Fetal Pain: Do We Know Enough to Do the Right Thing?

“…There is no indication of a laminar structure, a defining feature of maturity, in either the thalamus or the cortex. 13,14 The external wall of the brain is about 1mm thick and consists of an inner and outer layer with no cortical plate from which cortical layers will later develop. The cell density of the outer layer is much higher than that of a newborn or adult but contains large neurons that resemble those described in the older fetus.…”