Our previous studies have demonstrated that axons from grafts of embry
onic entorhinal cortex (EC) can reinnervate the deafferented zones in
the hippocampus and form synaptic connections with the host dentate gy
rus in adult mice and rats deprived of their own entorhinal inputs. He
re, we have examined the ability of the EC grafts to ameliorate defici
ts in spatial memory. Three months after transplantation, the grafted
rats and control animals were subjected to Morris water maze testing f
ollowed by histological examination. According to the exact position o
f grafts in the host brain, the rats with lesion and EC transplants we
re divided into two groups, one with EC grafts contacting both the hip
pocampus and overlying neocortex (n = 7, EC1) and another with EC graf
ts confined within the hippocampus (n = 6, EC2). While EC2 rats were s
till as impaired as those with lesion and transplants of non-entorhina
l cortex (n = 10, NEC) or with lesions only (n = 7, LES), the EC1 rats
performed better than the LES group. In a spatial memory trial, the E
C1 group made more crossings over platform site and showed more focuse
d search behavior than EC2, LES, NEC groups. The data suggest that EC
grafts could partially ameliorate the deficit in spatial learning beha
vior in the EC-lesioned adult rats. The requirement for the graft to c
ontact both the neocortex and the hippocampus suggests that the functi
onal effects may be exerted by the formation of new neocortical-EC gra
ft-hippocampal circuits. (C) 1998 Elsevier Science B.V.