Rf. Hevner et Hc. Kinney, RECIPROCAL ENTORHINAL-HIPPOCAMPAL CONNECTIONS ESTABLISHED BY HUMAN FETAL MIDGESTATION, Journal of comparative neurology, 372(3), 1996, pp. 384-394
Little is known about the timing or sequence of genesis of connections
between different areas of the developing human cerebral cortex. It h
as been shown that connections between areas V1 and V2 of the visual i
socortex are established at about 37 weeks of gestation (Burkhalter [1
993] Cerebr. Cortex 3:476-487), suggesting that cortico-cortical conne
ctions appear late in the 40-week human gestational period. However, t
here are indications from other studies that connections between subdi
visions of the hippocampal formation may be established much earlier,
by about 20 weeks of human gestation. To Investigate this possibility,
the lipophilic bidirectional tracer 1,1' dioctadecyl-3,3,3',3-tetrame
thylindocarbocyanine perchlorate (DiI) was used to study connections b
etween the entorhinal cortex, hippocampus, and temporal lobe neocortex
in paraformaldehyde-fixed postmortem fetal tissue. The DiI transport
revealed robust reciprocal connections between the entorhinal cortex,
hippocampus, and subiculum, which were consistently present at 19 week
s of gestation (the earliest age studied), and which were anatomically
similar to those in adult primates. Specifically, projections to the
hippocampus and subiculum originated from neurons in the entorhinal co
rtex (EC) layers 2 and 3, whereas reciprocal projections to the EC ori
ginated from pyramidal neurons in the cornu ammonis region CA1 and the
subiculum. In contrast, the perforant pathway projection from EC to t
he dentate gyrus, and all connections with the neocortex, reached only
rudimentary stages of development by 22 weeks of gestation (the lates
t age studied). These findings suggest that hippocampal pathways devel
op prior to isocortical pathways, and that reciprocal entorhinal-hippo
campal projections may be among the first cortico-cortical connections
to be established in the human brain. (C) 1996 Wiley-Liss, Inc.